R&D Archives

30/09/2024by EOS Intelligence EOS Intelligence No Comments

New Directions in Alzheimer’s Diagnostics: Will Blood Tests Replace CSF and PET?

Around three-fourths of dementia cases continue to remain undiagnosed even though the incidence of Alzheimer’s disease (AD) is rapidly growing across the globe. AD affects about 60-80% of dementia patients worldwide. Early diagnosis of AD is critical in forging beneficial medical care strategies and enhancing patient outcomes. Current AD diagnostic tests, such as cerebrospinal fluid (CSF) and PET scans, are either invasive or associated with side effects and are generally expensive. This calls for developing less invasive, safer, faster, and more accurate AD diagnostics, such as blood tests.

Blood-based tests promise accurate and non-invasive AD diagnosis

Researchers are developing less invasive and less costly blood tests that are likely to be more accurate than contemporary tests. There are currently two types of AD diagnostics blood-based tests: the phosphorylated tau217 (ptau217) test and the amyloid beta (Aβ) 42/40 plasma ratio test.

The ptau217 biomarker has the potential to differentiate AD from other neurodegenerative diseases, as ptau217 levels can be high in AD patients before the onset of clinical symptoms. Studies have proved that ptau217 tests can detect AD early on and monitor disease progression.

The Aβ 42/40 plasma ratio tests detect amyloid beta protein plaques in the brain that cause cognitive impairment. Due to the lack of a certified reference standard for measuring plasma Aβ42 and Aβ40’s absolute values, ptau217 may be better than an amyloid beta ratio test. However, both tests are accurate enough to diagnose AD.

Notably, ptau217 blood tests are believed to give up to 95% accurate results when coupled with CSF tests as against 90% accuracy of CSF when used as a standalone method. At the same time, amyloid beta (Aβ) 42/40 ratio tests are known to give around 80% accuracy in detecting amyloid positivity.

Many laboratories and diagnostic companies have designed or are designing ptau217 assays. C₂N Diagnostics, Quanterix, Quest Diagnostics, and Laboratory Corporation of America (LabCorp) offer ptau217 laboratory-developed tests (LDTs).

Low cost of blood-based AD tests can also be a growth-driving factor

A major push towards blood-based AD diagnostics comes from the tests’ lower cost in comparison to PET and CSF. The cost of blood tests typically ranges from US$200 to US$1,500, depending on the test provider.

The cost of PET ranges from US$1,200 to US$18,000, while the average price of CSF tests is around US$4,000 (in both cases, the actual cost depends on the type of facility, location, and the extent of insurance coverage).

As of 2023, Medicare and Medicaid covered PET scans for AD in the USA outside clinical trials. Therefore, AD patients need to pay around 20% of the PET cost, which translates to US$240-US$3,600, even after insurance coverage.

Considering the high share of dementia and AD cases remaining undiagnosed, there is a chance that the lower cost of blood-based tests can help contribute to higher accessibility to testing and ultimately improve the early detection rate.

Large AD diagnostic players partner with smaller ones to develop new tests

In an attempt to develop ptau217 assays, major diagnostics companies tend to recognize the development progress made by smaller players. ALZpath, a novel AD diagnostic solutions provider, is the pioneer of the ptau217 antibody, which helps in the early detection of the disease. Large players such as Roche and Beckman Coulter are enticed by the synergistic opportunities ALZpath offers.

In June 2024, Roche partnered with ALZpath, an early-stage biopharmaceutical company specializing in AD diagnostics, to launch the plasma ptau217 In-Vitro Diagnostic (IVD) test. As per the partnership, Roche will use ALZpath’s ptau217 antibody to design and commercialize an IVD test to detect AD with the help of Roche’s Elecsys platform.

In July 2024, Beckman Coulter also partnered with ALZpath to utilize ALZpath’s proprietary ptau217 antibody to detect AD on Beckman Coulter’s DxI 9000 Immunoassay Analyzer.

AD diagnostics firms receive funding from various sources, including drugmakers

Constantiam Biosciences, a bioinformatic analysis firm, received a US$485,000 Phase 1 SBIR grant (Small Business Innovation Research) from the National Institute on Aging to develop a tool for deciphering risk variants pertaining to AD and related dementias (AD/ADRD) in September 2024.

Biogen and Eli Lilly invested in the Diagnostics Accelerator, a funding initiative started in 2018, at the Alzheimer’s Drug Discovery Foundation (ADDF) in 2020. The Diagnostics Accelerator has invested over US$60 million across 58 projects, most of which are blood tests. In its Q4 2023 earnings call, Biogen emphasized its support for developing tau biomarker diagnostics and pathways. Its partner, Eisai, has invested around US$15 million in C₂N Diagnostics and collaborated with IVD companies such as Sysmex, among others. In September 2024, ADDF invested US$7 million in C₂N Diagnostics to further develop blood-based AD detection tests.

Other investors have also identified the opportunities AD diagnostic offers. A 2024 market research report by Market Research Future estimated that the AD diagnostic industry would nearly double, from US$4.5 billion in 2023 to US$8.8 billion in 2032.

FDA stands as an accelerating force for blood-based tests via breakthrough device designation

For a while now, the FDA has been granting breakthrough device designation (BDD) to devices that could address life-threatening diseases with unmet medical needs. BDD facilitates the expedited development, review, and assessment of medical devices, ensuring quicker access for patients and medical professionals. It would not be too ambitious to conclude that strong positive evidence from several uses and studies of ptau217 tests is likely to compel the FDA to approve them for use in the near future. The first sign of this is that the FDA is granting BDD status to multiple ptau217 blood tests.

In March 2024, the FDA granted BDD to Simoa ptau217 by Quanterix. This blood test can detect AD in patients with cognitive ailments even before signs and symptoms start to appear.

In April 2024, the FDA gave BDD to Roche’s Elecsys ptau217 plasma biomarker test to augment early diagnosis of AD. Roche partnered with Eli Lilly to develop this blood test that will widen and accelerate AD patients’ access to diagnosis and suitable medical attention and care.

In early 2019, the FDA gave BDD to C₂N Diagnostics’ blood test to detect AD. The BDD status of AD blood tests will likely accelerate the development, review, and assessment processes of these tests, improving patient outcomes.

Some FDA-approved AD drugs have used blood tests in clinical trials. Eli Lilly’s Kisunla and Esai/Biogen’s Leqembi have successfully utilized C₂N Diagnostics’ Precivity-ptau217 blood biomarker in their clinical trials. The FDA approved both drugs to manage AD. This improves the chances of this blood test getting approved by the FDA.

Lumipulse G β-Amyloid 1-42 Plasma Ratio test by Fujirebio Diagnostics received BDD from the FDA in 2019. The company submitted an FDA filing for the Lumipulse G ptau217/β-Amyloid 1-42 Plasma Ratio IVD test in September 2024. If approved, this test will become the first commercially available blood-based IVD test in the USA to detect AD.

EOS Perspective

There has been considerable progress in developing blood-based assays for AD diagnosis by pharma and diagnostics companies. However, a good portion of the liability for their products not reaching market readiness faster lies (and will probably remain to lie) on the approving authorities that are unable to accelerate the administrative steps.

Some blood tests, such as PrecivityAD, are approved for safe use in the EU but are still not in the USA. While such approval is typically a time-consuming process and requires a thorough investigation, the blood tests will enter the market at a larger scale across several geographies only if the authorities fast-track their approvals. This is particularly applicable to blood tests previously successfully used in clinical trials for approved AD drugs and for tests that have already attained BDD status from the FDA.

As an example, PrecivityAD by C₂N Diagnostics received BDD status in 2019 from the FDA. However, the FDA has still not approved the blood test for safe use in the USA. This is still despite the fact that PrecivityAD and other C₂N Diagnostics’ assays have been utilized in over 150 AD and other research studies across the USA and abroad. FDA’s time-consuming and lengthy review procedures and bureaucratic reasons are some of the factors responsible for the delay in approval. In addition to this, C₂N Diagnostics needs to submit some more evidential data pertaining to the accuracy of PrecivityAD, which is likely to take time to produce.

These procedural and administrative impediments, along with the time taken by the device makers to present the data to the FDA, will likely continue to put a brake on the blood-based tests becoming available to patients in the near future.

The situation will remain so, given the FDA’s recent decision to regulate new LDTs involving diagnostic tests that use body fluids such as blood, saliva, CSF, or tissue on similar lines as medical devices (meaning LDTs must comply with the same standards as medical devices). As per this regulation, LDTs need to prove the accuracy of their tests. This decision will have both winners and losers in the AD stakeholder ecosystem.

Researchers and physicians are looking at this regulation with a positive stride as this step will reduce the number of tests with unconfirmed accuracy from the market in the USA. This is undoubtedly a positive change for patients’ safety, reducing the number of misdiagnoses and accelerating correct diagnoses.

On the other hand, smaller start-ups and diagnostic companies are not likely to benefit from this decision as it will restrict the development of new innovative tests vis-à-vis large diagnostic companies. Overall, the decision will likely decelerate the approval of blood-based AD tests or at least will require much more paperwork and proof of accuracy from the device makers. This decision will take effect in multiple phases over four years, starting from July 2024.

On the research and development side of the Alzheimer’s disease diagnostics space, a certain level of symbiosis between drug producers and diagnostic solution providers will continue to impact the market positively. Drugmakers are partnering with or investing in diagnostic companies to leverage the latter’s innovative blood-based biomarkers (BBBM) technologies in the clinical trials of their own drug candidates. This trend is likely to continue.

Not only drugmakers but also more prominent healthcare diagnostics companies, such as Roche and Beckman Coulter, are partnering with early-stage biopharmaceutical companies, such as ALZpath, to develop and commercialize AD ptau217 tests. Collaborations such as these are a testimony to the fact that it is mutually beneficial for AD industry stakeholders to work in tandem to advance AD diagnostics research, a significant growth-driving factor for the market.

26/09/2024by EOS Intelligence EOS Intelligence No Comments

Phase 3 Drug Candidates – A Ray of Hope in Alzheimer’s Disease Bleak Treatment Landscape?

Many biopharmaceutical companies, such as AriBio, Annovis Bio, Athira Pharma, Cassava Sciences, and Alzheon, specializing in treating neurodegenerative diseases, are developing drugs for Alzheimer’s disease (AD) that are currently in phase 3 of clinical trials. If approved, these drugs can ameliorate the AD treatment approaches to a considerable extent. A major prerequisite to this is for concerned authorities to take concrete steps to fast-track clinical trials and increase AD research investment.

With only a 1% success rate of clinical trials in drug development until 2019, the AD treatment gap is alarming. A 99% failure rate means there is a very limited influx of new, more effective, and more advanced AD drugs into the market, and the gap between available treatment options and the rising number of AD cases is increasing.

The disease burden of Alzheimer’s will rise from US$1.3 trillion in 2020 to US$2.8 trillion by 2030 globally. With the rise in the aging population across the globe, the estimated number of AD patients will increase from 55 million in 2020 to 78 million in 2030.

However, recent drug approvals, such as Elli Lilly’s Kisunla (Donanemab) in July 2024 and Biogen/Eisai’s Leqembi (Lecanemab) in January 2023, bring a ray of hope for a new approach to AD treatment.

Initial hopes for new drugs can be premature

New drugs do enter the market from time to time. However, their impact on AD treatment in the long term is not always significant. An example of this is Biogen’s Aduhelm. Based on its ability to reduce amyloid protein in the brain, the FDA approved Aduhelm (Aducanumab) in 2021 in an accelerated approval route for AD treatment.

However, in 2024, Biogen discontinued the drug in the alleged desire to reprioritize its resources in AD treatment. Experts cite weak clinical evidence for efficacy, serious side effect risks, a high price point, and poor sales among the many reasons for Aduhelm’s withdrawal from the market.

AD drug candidates succumb to clinical failures

Eisai and Biogen have been working together since 2014 to develop and commercialize AD drugs. However, they have faced clinical drug failures, similarly to many other pharmaceutical companies during that time. For instance, they had to terminate Elenbecestat, one of their AD drugs, in phase 2 clinical trial in 2019 following an unfavorable risk-benefit ratio finding by the Data Safety Monitoring Board (DSMB).

Eisai launched its first AD drug, Aricept, an acetylcholinesterase inhibitor, in the USA in 1997 in collaboration with Pfizer. The annual peak sales of Aricept were US$2.74 billion before its patent expiry in 2010. However, Pfizer exited neuroscience drug research and development in 2018 after the failure of its AD drug candidates, such as Dimebon and Bapineuzumab.

Clinical challenges in Alzheimer’s research and reallocation of resources were among the other reasons for Pfizer’s exit from neuroscience R&D and drug development. Nevertheless, Pfizer did not desert the neuroscience space completely, rather forged a spin-off company called Cerevel Therapeutics in partnership with Bain Capital.

Phase 3 Drug Candidates – A Ray of Hope in Alzheimer’s Disease Bleak Treatment Landscape by EOS Intelligence

Recent drug launches focus on amyloid beta targeting mechanism

In January 2023, the FDA approved Leqembi (Lecanemab), a drug by Biogen and Eisai, for AD treatment. It is a monoclonal antibody that clears away the amyloid beta plaques known to cause cognitive impairment in AD patients. With MHRA’s (Medicines and Healthcare Products Regulatory Agency) approval of Leqembi, Great Britain becomes the first European country to authorize the drug for the treatment of early-stage AD as of August 2024.

In July 2024, the FDA approved Kisunla (Donanemab) by Eli Lilly to treat early-stage AD. The drug’s mechanism of action is the same principle as that of Leqembi, an amyloid beta protein plaque targeting mechanism. Kisunla becomes the third anti-amyloid drug approved for AD treatment, following Aduhelm (now discontinued) and Leqembi. Both Kisunla and Leqembi drugs carry the risks of the formation of temporary lumps in the brain that can be fatal. Therefore, physicians advise regular brain MRIs to alleviate this risk. Neurologists and researchers are in disagreement over whether the benefits offered by these drugs are clinically meaningful.

Researchers are still studying the side effects of these two drugs. Prescribing them requires confirmation of the presence of amyloid protein in the brain. Therefore, PET scans and CSF tests are required before such a prescription.

The FDA has approved both drugs in the USA for intravenous infusions (IV) in the early stages of AD. Kisunla is administered every four weeks instead of every two for Leqembi. Therefore, Kisunla offers greater convenience compared to Leqembi.

Experts from Bloomberg Intelligence suggest that Eli Lilly will likely surpass Biogen and Eisai’s reign at the top of the AD drug market by capturing around 50% of the US$13 billion market globally by 2030. This is partly because of Kisunla’s convenient dosing and the fact that AD patients can stop taking the drug after the amyloid levels touch the clearance threshold.

Newer therapeutic approach-based drugs are in phase 3 clinical trials

Apart from the amyloid beta therapeutic approach, AD researchers are exploring the role of other mechanisms in AD treatment, such as anti-tau antibodies, neurotransmitter receptors, and synaptic plasticity or neuroprotection. Drugs based on these mechanisms are currently in phase 3 of clinical trials.

The Washington University School of Medicine’s DIAN-TU (Dominantly Inherited Alzheimer Network Trials Unit) trial is testing Lecanemab plus Eisai’s investigational anti-tau antibody E2814 in patients with early-onset AD caused by a genetic mutation. E2814 prevents the spreading of tau seeds in the brains of AD patients. This drug is in phase 3 clinical trial. The clinical study commenced in June 2024 and will complete by November 2029.

ACP-204 by Acadia Pharmaceuticals is also in phase 3 clinical trial for AD. The agent acts as an inverse agonist at the 5-HT2A serotonin receptor. FDA has approved Acadia’s previous 5-HT2A inverse agonist, Nuplazid, for Parkinson’s disease psychosis. ACP-204 will be the first drug for AD treatment in Acadia’s product portfolio if approved.

Another drug in phase 3 trial is AriBio’s AR1001, a phosphodiesterase-5 (PDE5) inhibitor. Apart from AR1001, two more AD drugs are in AriBio’s pipeline, AR1002 and AR1003 that are currently under the investigational new drug-enabling stage of clinical trials.

For better patient outcomes, researchers are attempting to develop AD drugs with non-invasive modes of administration that are likely to be less expensive and equally effective compared to AD drugs administered intravenously.

The safety and effectiveness of oral therapy candidate Buntanetap, developed by Annovis Bio, are comparable in people with early onset AD regardless of whether they do or do not carry a genetic risk factor APOE4. That is according to new data from a phase 2/3 clinical trial that tested three doses of Buntanetap against a placebo in more than 300 patients with the neurodegenerative disease. Buntanetap modulates protein production to reduce clumping. The competitive advantage of Annovis Bio over its peers is the fact that Buntanetap targets multiple proteins in the brain, such as amyloid beta, tau, alpha-synuclein, and TDP43, making it more effective than AD drugs that target a single protein.

Apart from Buntanetap, Annovis Bio has another oral drug to treat advanced AD and dementia in its pipeline, ANVS301, which is in phase 1 of clinical trial. In July 2024, Annovis Bio received FDA approval to transition to a new solid form of Buntanetap in future clinical trials allowing the company to refine its drug formulation, potentially improving its efficacy and safety profiles.

Another promising AD drug candidate, Fosgonimeton by Athira Pharma, is a small-molecule positive modulator of the hepatocyte growth factor (HGF) system, previously showing neuroprotective, neurotrophic, and anti-inflammatory effects in preclinical models of dementia. This drug is in phase 3 clinical trial. Athira Pharma ended 2023 with a strong balance sheet, signaling its better financial position to augment its ongoing pipeline development.

Eli Lilly’s new drug Remternetug works as pyroglutamyl (3)-amyloid beta-protein (3-42) inhibitors, positioning it as a promising AD drug. Remternetug will join Eli Lilly’s portfolio as a second AD drug if approved.

Simufilam by Cassava Sciences is a proprietary, small-molecule oral drug that restores the normal shape and function of altered filamin A (FLNA), a scaffolding protein, in the brain. It is now in phase 3 clinical study to test this new and promising scientific approach to treating and diagnosing AD. The mechanism of action of this drug involves stabilizing a critical protein in the brain instead of removing it. This novel approach distinguishes Cassava Sciences’ drug from other treatments that predominantly focus on amyloid-beta or tau proteins. In May 2024, Cassava Sciences raised US$125 million by selling its stock to shareholders. The funds will be utilized for the continued development of Simufilam.

Valiltramiprosate by Alzheon is potentially the first oral disease-modifying treatment for AD. Valiltramiprosate is well differentiated from plaque-clearing antibodies in development for AD due to its novel mechanism of action, oral mode of administration, and potential efficacy in a genetically targeted population. In October 2017, Valiltramiprosate/ALZ-801 received FDA Fast Track designation for AD investigation. Due to Alzheon’s significant progress in AD drug development, the company has attracted a lot of investors since 2022. Alzheon received US$100 million in June 2024 in Series E venture capital funding which will be utilized to further develop and commercialize Valiltramiprosate. This is in addition to US$50 million received in series D round of funding in 2022.

Big names dominate the competition, with clinical trials in progress by smaller biopharma players

On the competitive landscape front, the AD drug market is highly competitive, with many pharmaceutical companies financing R&D to engineer new drugs that could potentially delay the progression of AD and/or restore neuronal health. The global AD therapeutics market size was US$4.8 billion in 2023 and will surpass US$7.5 billion by 2031, as per Towards Healthcare, a healthcare consulting firm.

A couple of large players still dominate the global AD therapeutics market. Interestingly, they are not the only ones active in the AD treatment development, as several smaller biopharmaceutical companies that specialize in neurodegenerative disease treatment are working on AD drugs (many currently in phase 3 of clinical trials).

High R&D costs are a considerable factor in slowing the progress down

Between 1995 and 2021, the cumulative private spend (total R&D expenditure by pharmaceutical companies, does not include federal funding) on clinical stage R&D for AD was US$42.5 billion, with the largest share of 57% (US$24.1 billion) incurred during phase 3. During the same period, the FDA approved 878 drugs across all therapeutic areas; only six of these drugs were for AD treatment (four cholinesterase inhibitors [ChEIs], memantine, and aducanumab). These statistics speak volumes of the complex, expensive, time-consuming, and predominantly unsuccessful nature of AD clinical trials. This ultimately leads to exorbitant prices of AD drugs.

A range of factors drive the R&D costs and, in turn, the price of AD drugs. A significant component here is patient screening, which contributes to 50-70% of the cost. Patient recruitment and retention are also challenging, given the considerable length of such trials.

Moreover, patient recruitment challenges stunt the progress of AD clinical trials. The recruitment rate for AD clinical trials is as low as one patient per site per month. In terms of eligibility, 99% of AD patients who are eligible for participation in a clinical trial never consider taking part. This further increases the time taken to conduct AD clinical trials.

EOS Perspective

After decades of failure in clinical trials, two anti-amyloid AD drugs, Kisunla and Leqembi, are available in the market, forming a duopoly in the USA. There are several promising drugs in phase 3 clinical trials with a new mechanism of action apart from amyloid beta protein inhibitors. However, the disease management landscape is prone to unforeseen changes, such as the withdrawal of drugs owing to safety, efficacy, and pricing issues.

The AD treatment landscape faces challenges such as drug inefficacy, complex pathophysiology of AD, expensive and time-consuming clinical trials, delays in diagnosis by physicians, behavioral changes and deteriorating mental health of AD patients, and severe side effects of medications. These challenges will continue to impede the development of new disease management approaches.

An issue that is very likely to continue to challenge progress in developing better treatment options for AD is the severe lack of funding. Dementia research is extremely underfunded compared to HIV/AIDS, cancer, and COVID-19 in the USA. Irrespective of the fact that the deaths attributed to AD are on par with cancer, the difference between the annual US federal government funding for AD vis-à-vis cancer is strikingly huge.

AD drug development is a tough market to operate in. The ongoing issue with AD research funding persists, and there do not seem to be changes in federal funding soon. On top of that, the slow progress in successful R&D and many failed clinical research trials will likely make private-sector investors hesitate or withdraw.

In addition to this, AD drug manufacturers will also continue to face the challenge of low to modest drug sales due to poor adoption rates stemming from issues like restricted coverage.

As of June 2023, Medicare was covering AD drugs that slow down the progress of the disease provided a physician agrees to the collection of real-world evidence of these AD drugs, as per the Centers for Medicare & Medicaid Services (CMS). However, there is a significant underlying problem with drugs for AD treatment. When the drug finally enters the market, patients cannot afford the treatment, and the coverage is restricted and sometimes withdrawn. There is no foreseeable change to this impasse, and hence, the AD treatment development is likely to be slow.

If reimbursement of AD drugs is removed, patients are likely to stop administering AD drugs altogether and adopt alternative healthcare resources such as antidepressants, as found in a 2021 study by researchers from Paris-Saclay University and Memory Center of Sainte Périne Hospital in France.

The reluctance of payers to cover the treatment cost for AD is influenced by several factors beyond just the high cost of the drug. Factors include cost-effectiveness of treatments, uncertain long-term safety and efficacy benefits of treatments, clinical guidelines and recommendations, availability of alternative treatments including generics (from drug makers such as Cadila, Cipla, Dr. Reddy’s, among others), and regulatory and reimbursement policies.

The future of AD treatment approaches will continue to remain bleak, and patients will be left with only a few available drug options unless the right authorities set out a plan for fast-track clinical trial processes, increase AD research investment, and support broader insurance coverage.

25/07/2024by EOS Intelligence EOS Intelligence No Comments

Lessons for Africa: To-do’s from India’s Successful Vaccine Journey

India, still a developing country, has achieved tremendous success as the world’s largest vaccine producer. This accomplishment leads to many lessons that India can offer to other low- to middle-income economies across the globe, such as Africa, looking to ramp up their vaccine industry. The African continent should capitalize on this opportunity and seek guidance from India, considering that India’s pharma and vaccine sectors are four to five decades ahead of the African continent.

How did it all begin for the Indian pharma and vaccine sectors?

The Indian pharma industry is more than a century old, with the first pharmaceutical company founded in 1901 and started operations in Calcutta. Till 1970, the Indian pharmaceutical industry comprised foreign players with very few local companies. However, driven by the purpose of the Swadeshi (meaning ‘of one’s own nation’) movement during the pre-independence era, some pharmaceutical manufacturing firms were founded in India. Established in 1935 in Bombay, Cipla was one such company, which is now a multinational pharmaceutical firm.

Apart from pharma companies, the presence of the Bombay-based Haffkine Institute (founded in 1899) and Coonoor-based Pasteur Institute of India (founded in 1907) solidified the country’s vaccine industry foundation. These institutes manufactured anti-plague, anti-rabies, smallpox, influenza, and cholera vaccines, among others. Nevertheless, the British colonial government in India withdrew the funds during World War II, which led to the subsidence of a few of these institutes.

The Indian pharma industry’s dynamics began to change, with recognition given to process patents instead of product patents. This created an opportunity for local pharma companies to reverse-engineer branded drugs’ formulations. It also allowed the creation of low-cost medicines since the producers did not have to pay royalties to original patent holders. It fueled the generics market growth in India, along with improving the capabilities of the manufacturers to produce high volume at low cost, thereby increasing the cost-effectiveness of the products. This was followed by the exit of foreign pharma players from the country with the removal of the Indian Patents and Design Act of 1911 and the implementation of the Government’s Patents Act of 1970.

This article is part of EOS' Perspectives series on vaccines landscape in Africa. 
Read our other Perspectives in the series:

Vaccines in Africa: Pursuit of Reducing Over-Dependence on Imports

Why Can India’s Vaccine Success Story Be a Sure Shot Template for Africa?

The structural change in the Indian pharma industry was evident from the drastic increase in the number of domestic companies from 2,000 in 1970 to 24,000 in 1995, leapfrogging 12-fold in a span of 25 years.

Additionally, driven by public sector investment and the central government’s prioritization of localized vaccine and drug production, India had over 19 public sector institutes and enterprises by 1971 that produced vaccines and generic drugs. These public sector institutes included Gurgaon-based Indian Drugs and Pharmaceuticals Limited and Pune-based Hindustan Antibiotics Limited.

Some pharma companies entered the export market owing to the 1991 liberalization of the Indian economy, the experience gained from producing cost-effective generic drugs, and global expansion. With this step, the Indian vaccine industry forayed into the international market between 1995 and 2005.

The reintroduction of the product patent system encouraged foreign pharma firms to return to India as the 2005 Patents (Amendment) Act prevented domestic pharma companies from reverse engineering formulations of branded medicines protected by patents to produce generic drugs.

In the pursuit of staying competitive with their foreign peers, Indian pharmaceutical companies focused on improving R&D thereby increasing investments in this space from 2005 to 2018.

What did India do right in vaccine manufacturing?

From investing in education and R&D to making necessary policy changes conducive to the growth of a sustainable and resilient vaccine sector, the Indian government has always been at the forefront of reducing overall pharmaceutical costs and nurturing the pharma industry.

Experience, expertise, and conducive policies enabled India to achieve cost-effectiveness

Indian government’s concrete action in strategy and policy-making has empowered the pharma industry to grow in a conducive environment. These conditions enabled the sector to become cost-effective by producing low-cost generic medicines and vaccines at high volumes.

This is evident from the fact that Invest India, the country’s investment promotion agency, states that producing pharmaceuticals in India is 33% cheaper than in Western markets due to labor costs being 50-55% lower. The cost of conducting clinical trials in India is also much lower, approximately 40%-80% cheaper when compared to Western markets, according to a 2010 article by the International Journal of Pharmacy and Pharmaceutical Sciences.

Indian pharma firms sometimes reverse-engineer medicines produced by companies making branded drugs and sell the formulation at a much-reduced price. The unique selling proposition of the Indian pharma industry has always been high volume coupled with low costs to make its products more affordable and accessible to patients across low- to middle-income strata of society.

Investments towards a robust scientific workforce helped reduce API import dependencies

Backed by the central government’s prioritization of domestic vaccine and drug production, some pharma companies in India started manufacturing raw materials or key starting materials to minimize the dependencies on API imports.

Other initiatives to strengthen the foothold of the Indian vaccine sector were directed towards building a solid talent pool of professionals who could develop drugs and vaccines independently rather than copy the processes from branded medicines. A result of this approach was the Lucknow-based Central Drug Research Institute (CDRI), which was founded in 1951 and continues to be one of the leading scientific institutes in India.

With the creation of the Department of Biotechnology (DBT) in 1986, India took another massive step towards progressing its pharma industry. Since then, DBT has been at the forefront of providing financial and logistical support for vaccine development and production using new and advanced technologies. The organization is also involved in creating biotech training programs for universities and institutes across India.

Lessons for Africa To-do’s from India’s Successful Vaccine Journey by EOS Intelligence

What can Africa learn from India’s experience?

It would be too ambitious to anticipate Africa replicating the Indian vaccine sector’s strategies and mechanisms in every way and detail. Although the two regions share enough similarities regarding disease profiles, geographies, climates, economies, etc., differences in competition, technology, and market dynamics cannot be ignored.

These differences could benefit and challenge the vaccine sector in Africa. The region must prioritize the creation of a resilient, sustainable, and robust life sciences ecosystem that will support the pharma, medical technologies, and vaccine sectors in the long run.

Development of a strong life sciences ecosystem that nurtures the overall vaccine sector

Africa needs to form close ties with multiple supporting networks, similar to how the Indian vaccine producers networked with the local biosciences ecosystem. These supporting networks must be associated with the production of multiple pharmaceutical products for a region, building a strong scientific labor force alongside reinforcing its regulatory system.

Higher level of autonomy for the leadership teams of government-led vaccine facilities

One of the key learnings from the pitfalls of India’s vaccine sector is that the executive/leadership teams of government-owned vaccine facilities should receive a higher level of autonomy. Interferences from government agencies should be avoided to the maximum extent possible. A classic example from the Indian market is the 2020-2021 downfall of HLL Biotech Limited which could not produce any COVID-19 vaccine owing to government interferences in the technology upgrade and production-related decisions.

EOS Perspective

For the African vaccine development and production industry to embark on a path of growth, it is imperative to learn from the valuable lessons available. However, with limited financial resources and insufficient infrastructure, it is crucial to prioritize the actions taken to ensure maximum progress.

To start building a favorable environment, it might be beneficial for the African markets to develop policies emphasizing process patents more than product patents, at least in the initial few years. This could be akin to regulations in the Indian pharma sector of 1970-1995, which proved quite effective and could fuel the growth of the generics market in Africa. Creating such an environment would waive off patent protection of branded drug manufacturers initially so that the local pharma companies can produce medicines at a low cost without paying royalties for copying the drug formulations of the branded drugs. Therefore, Africa can focus on building their generics market first and utilize the profits from there to reinforce the vaccine industry.

Secondly, African governments should initiate expanding the number of technology transfer hubs across the continent that focus not only on mRNA-based vaccines but also on newer DNA-based vaccines that are more suited for the African climate. Partnerships and collaborations with research institutes that are already working towards this goal can be a good first step.

One crucial step, which should not be delayed, is building a robust, skilled workforce to drive the sector development. Unfortunately, most African countries’ current education curricula are not in sync with the continent’s needs for vaccine manufacturing. Therefore, Africa urgently needs investment in education from various sources to develop the backbone of the vaccine industry so that the new education system can produce employable graduates in this field. It is important to note that the African governments should take a significant portion of this responsibility.

To begin with, new graduates can be something other than tertiary-educated, highly specialized professionals, such as PhDs. Rather than that, some form of vocational training in vaccine manufacturing or bachelor’s programs in relevant subjects, such as pharmacy, chemistry, etc., would help produce sufficiently skilled labor. This manpower can work and train further on the job under the guidance and supervision of foreign high-level talent and local high-level scientists who are present in the continent relatively sparsely.

These vocational programs should be designed in a collaborative effort between educational institutions and the existing and new vaccine manufacturing facilities in Africa. This would increase the chances of the African manufacturing facilities absorbing the graduating trainees.

India’s education evolution demonstrates the significance of having domestically bred relevant talent to augment and strengthen its own pharma and vaccine sector. This can empower Africa to curb the costs associated with foreign talent hunting and be more resilient to situations such as staff shortages, foreign staff availability fluctuations, etc.

Moreover, it is the responsibility of African governments to support the creation of jobs in vaccine manufacturing and R&D to attract the newly-trained workforce. A proven approach to this is to offer incentives for employing local talent to foreign and domestic investors who intend to set up vaccine facilities in the region. The incentives could range from tax rebates, exemptions, or credits, to offering employee training grants, subsidies for insurance coverage, etc. If this can encourage the creation of jobs in the sectors, young Africans will likely be keen on enrolling in related vocational programs.

Looking at the long-term objectives for the continent’s vaccine industry path, Africa’s primary aim should be to meet its own domestic vaccine needs in terms of both volume and disease spectrum.

Africa can learn critical lessons from India’s strengths and weaknesses in the vaccine sector. The weight of kick-starting the industry development inevitably lies on the African governments’ shoulders, and the sector will not develop on its own. It is high time for stakeholders, such as state governments, regulatory bodies, institutes, pan-African organizations, and local pharma companies, to speed up the process of absorbing and implementing these lessons. It is the only way to achieve the goal of 60% domestic vaccine production by 2040.

18/07/2024by EOS Intelligence EOS Intelligence No Comments

Why Can India’s Vaccine Success Story Be a Sure Shot Template for Africa?

Africa is currently facing significant challenges related to limited accessibility to vaccines as well as ongoing vaccine hesitancy. African CDC has identified these problems and is taking concrete steps to achieve its 2040 target of 60% of vaccines available on the continent to originate from domestic production. India is one of the key countries invested in the growth of Africa’s healthcare sector both financially and logistically. Due to similar geographies, climates, disease prevalence, and economies, Africa could take guidance, collaborate, or replicate Indian vaccine manufacturers’ strategies and mechanisms to scale up its vaccine sector.

Africa has one of the lowest average vaccine administration rates globally

Unbalanced access to vaccines in Africa compared to other regions became quite vivid during the COVID-19 pandemic. Africa’s average number of coronavirus vaccine doses administered per 100 people was 54.37 as of March 15, 2023. Seychelles administered the highest number of vaccine doses at 205.37 and Burundi the lowest at 0.27.

In contrast, the world average stood at 173, with high-income countries such as the USA and Canada administering 191 and 258 vaccine doses per 100 people, respectively. Interestingly, Cuba, despite being an upper middle-income economy, administered 385, a higher number of doses per 100 people than some high-income countries.

Even some low-income economies such as Vietnam (276), Bhutan (264), Bangladesh (218), Nepal (213), and Sri Lanka (184), among others, administered a higher number of coronavirus vaccine doses than the world average (173), and far more than Africa’s average.

These stark variations in the vaccine administration rates across countries could be attributed to the lack of easy accessibility, especially in Africa, apart from other factors such as vaccine hesitancy.

Africans’ vaccine hesitancy slows down the uptake of vaccination

Vaccine hesitancy is caused by several factors such as personal beliefs, misinformation or myths, healthcare infrastructure and access, religious and cultural beliefs, and vaccine safety concerns. These are typically the main reasons for vaccine hesitancy according to an October 2023 article published by ThinkGlobalHealth, and several of these reasons are likely to apply to the African continent.

In addition to these, another critical factor that cannot be ignored is people’s lack of trust in the health ministries, a relevant aspect in some African countries such as South Africa. This was largely due to the ministries’ involvement in procurement corruption of COVID-related aid according to an article published by GlobalData in November 2023.

Africa’s low vaccine administration rate is driven by limited accessibility

One major reason for the vaccine’s low administration rate in Africa is the limited accessibility to vaccines. This has been an ongoing issue on the continent and was not just limited to pandemics such as COVID-19 and Ebola.

The African continent is overdependent on vaccine imports, with 99% of its vaccine needs being satisfied from abroad. With a total of 13 operational production facilities across the continent, the current vaccine manufacturing industry is in its infancy in Africa and produces 1% of the continent’s vaccine supplies.

African countries have recognized this issue and begun working towards its goal of meeting 60% of the continent’s vaccine needs domestically by 2040, with interim targets of 10% by 2025 and 30% by 2030.

This article is part of EOS' Perspectives series on vaccines landscape in Africa. 
Read our other Perspectives in the series:

Vaccines in Africa: Pursuit of Reducing Over-Dependence on Imports

With some local talent available, Africa needs the right development template

While the local vaccine industry is underdeveloped, to say the least, the continent is not entirely without the talent required to produce home-grown vaccines and other pharmaceutical products such as test kits. For instance, Senegal-based Pasteur Institute developed a US$1 finger-prick at-home antigen test for COVID-19 in partnership with Mologic, a UK-based biotech company. Although the funding came partially from the UK, local talent was predominantly utilized.

To establish a sustainable vaccine sector, Africa does not need to reinvent the wheel. It could utilize lessons and success stories of other countries that have built this industry and share similarities with the African continent.

India is one such country with a vast size, diverse cultures, geography, and administrative structures under one roof, and has a tropical climate and disease profile similar to those in Africa. Additionally, India’s symbiotic relationship with the African healthcare sector would also play a significant role in empowering Africa to leverage the expertise of the Indian vaccine sector. This could be a step in the right direction for the African continent to achieve vaccine sovereignty.

Why Can India’s Vaccine Success Story Be a Sure Shot Template for Africa by EOS Intelligence

Africa’s partnership with India in healthcare is not new

Africa has a long-standing healthcare partnership with India, as the latter has been the largest supplier of generic medicines to Africa. Additionally, some US$3.4 billion worth of pharma products, i.e. close to 20% of India’s total pharma exports, went to African countries as of 2018. In 2020-2021, India’s pharma exports to Africa amounted to US$4.3 billion as per the Pharmaceuticals Export Promotion Council of India (Pharmexcil).

Between 2010 and 2019, India was also the third-largest contributor to Africa’s healthcare investment landscape, after the UK and the USA. During this period, India invested around US$210 million out of a total of US$1.1 billion in global investments into Africa’s healthcare sector, accounting for a 19% share.

In the past, African pharma companies have relied on Indian organizations to pivot and streamline their business in difficult times. For instance, South Africa-based Aspen Pharmacare could not sell a single dose of its COVID-19 vector vaccine owing to multiple factors, such as the rising popularity of mRNA vaccines. Ultimately, the company partnered with the Serum Institute of India (SII) in August 2022 to produce its vaccines to minimize business loss and idle production capacity. This is just one example showcasing opportunities where African vaccine producers collaborated with Indian vaccine makers. This kind of collaboration can also become a source of guidance and knowledge on how to create own sustainable ecosystem for vaccine production.

Collaborations between Africa and India have also extended beyond adverse situations. One example of this is a partnered research to produce a DNA-based dengue vaccine. Scientists from Bangalore and Goa in India and Nairobi and Cameroon in Africa have been working together in a partnership called the India-Africa Health Sciences Collaborative Platform (IAHSP), set up in 2019. The partnership results from a collaboration between India’s ICMR (Indian Council of Medical Research) and the African Union to create this DNA-based dengue vaccine, among other research work involving antimicrobial resistance, per a January 2022 Springer Nature article.

Furthermore, in December 2020, the Indian Healthcare Federation (NATHEALTH) and the African Health Federation (AHF) partnered to foster investment in healthcare and thus promote business opportunities in healthcare between India and Africa.

India’s pharma industry has merits to learn from

The Indian vaccine production sector is rapidly gaining steam in the global market and outpacing multinational players in this industry. A few prominent Indian vaccine producers, such as SII, Bharat Biotech (BBIL), and Biological E, have captured a considerable market share globally.

Interestingly, over 60% of the global vaccine needs in terms of volume are being satisfied by only five producers globally. Three of these five producers are based in India: Pune-based SII, Hyderabad-based BBIL, and Mumbai-based Haffkine. SII tops the list of these five global producers with a 28% volume share globally, and BBIL (9%) shares the third spot with Sanofi, followed by Haffkine (7%), as of 2019.

For many years, India has been supplying cost-effective and high-quality generic medicines and vaccines, which has earned the country the title of ‘pharmacy to the world’. The title is not exaggerated, as India alone accounts for 62% of global vaccines and 20% of global generic drugs’ production by volume as of 2023. The Indian pharma sector holds the third rank by production volume and tenth by value globally.

With an 18% share of pharmaceutical exports and vast needs, Africa is the second-largest importer of pharmaceutical products from India as of 2019.

Indian vaccines’ success in Africa proves that Indian producers understand African needs

In its quest to develop its own vaccine production sector, Africa can learn a host of aspects of vaccine production from India. This includes but is not limited to the cost-effectiveness of vaccines against diseases such as COVID-19, rabies, diphtheria, pertussis, tetanus (DPT), human papillomavirus (HPV), malaria, Ebola, and meningitis. India is four to five decades ahead of Africa in vaccine manufacturing and has already done its homework on how to do it right. That’s a useful source of knowledge for Africa’s budding industry, especially since Indian-made pharma products tend to align well with the needs of the African continent.

Serum Institute of India’s (SII) foothold in Africa

SII is now the largest vaccine producer by the number of doses manufactured and sold worldwide (over 1.6 billion doses across 170 countries in 2020), including for polio, diphtheria, tetanus, pertussis, haemophilus influenzae type b (Hib), BCG, r-Hepatitis B, measles, mumps, rubella, as well as pneumococcal and COVID-19 vaccines. According to estimates, nearly 65% of children across the globe receive at least one vaccine produced by SII.

SII has a strong foothold in Africa, with several of its vaccine products being extensively used or developed specifically for the continent’s needs.

MenAfriVac, manufactured by SII, is a vaccine to prevent meningitis and was rolled out in Africa in 2010. The vaccine was developed specifically to curb the spread of meningitis in Africa to cater to the vaccine needs of its population. The price of the vaccine is less than US$0.50 per dose, with an efficacy of 52% among 12–23-month-old children and 70% among older children and adults. Thanks to the vaccine, over 152 million people were inoculated by MenAfriVac by the end of 2013, enabling the elimination of meningitis epidemics in 26 African countries.

Another example of an India-made vaccine to particularly reduce Africa’s disease burden of malaria and cater to its people’s vaccine needs is R21/Matrix-M. SII, along with Oxford University, has produced this malaria vaccine using the technology of Novavax, a US-based biotech company. The vaccine has been approved for use by some African countries’ regulatory authorities, such as Ghana, Nigeria, and Burkina Faso, as of December 2023. According to a January 2024 press release by SII, the vaccine showed efficacy of around 78% in the age group between five- and seventeen-months children in Burkina Faso, Kenya, Mali, and Tanzania over the first year. The company is planning to roll out the 25 million vaccines produced in the coming four to five months.

In December 2022, SII acted rapidly on the Sudan Ebolavirus outbreak in Uganda by sending over 40,000 doses of the investigational ChAdOx1 SUDV vaccine in a record time of 80 days after WHO declared the epidemic.

These are some examples showcasing the fact that SII, along with other Indian producers, understands Africa’s vaccine needs, which is evident from the success of these vaccines in Africa. Consequently, it makes logical and economic sense for Africa to learn from Indian vaccine manufacturers to develop low-cost, effective vaccines.

Apart from successfully selling its vaccines in Africa, SII also actively contributes to the knowledge transfer into the continent. In January 2024, SII partnered with the Coalition for Epidemic Preparedness Innovations (CEPI) to foster low-cost vaccine production in Global South countries, including Africa (also comprising Latin America and the Caribbean, Asia (excluding Israel, Japan, and South Korea), and Oceania (excluding Australia and New Zealand)) to curb the outbreak of life-threatening diseases. CEPI is a global organization formed as a result of an international collaboration between public, private, philanthropic institutions and NGOs.

CEPI has three other members apart from SII: South Africa-based Aspen Pharmacare, Senegal-based Institut Pasteur de Dakar, and Indonesia-based Bio Farma. With this partnership, CEPI intends to capitalize on SII’s expertise in making affordable, cost-effective vaccines in record time. In this pursuit, CEPI is investing US$30 million so that vaccine developers who are already partners of CEPI can expedite technology transfers to SII within days or weeks of any outbreak. This will enable SII to produce vaccines against the impending disease.

Bharat Biotech’s (BBIL) foothold in Africa

With over 145 global patents and a portfolio comprising over 16 vaccines, BBIL has sent over 6 billion doses of vaccines to 125 countries worldwide. BBIL has produced vaccines against influenza H1N1, rotavirus, Japanese encephalitis (JENVAC), rabies, chikungunya, zika virus, and cholera. The company is also the creator of the world’s first tetanus toxoid conjugated vaccine for typhoid. In addition to these, BBIL has manufactured WHO pre-qualified vaccines, such as BIOPOLIO, ROTAVAC, ROTAVAC 5D, and Typbar TCV against polio, rotavirus, and typhoid infections, respectively.

BBIL has also been offering its products to Africa. In one of the recent examples, the company delivered its rotavirus oral vaccine, ROTAVAC, to Nigeria to immunize the country’s children in August 2022. The vaccine is expected to minimize the occurrence of the disease and death due to rotavirus among Nigerian children below the age of five years by at least 40%, according to research by the Johns Hopkins Bloomberg School of Public Health.

Another example of a vaccine made by BBIL that is aligned with the needs of the African population is MTBVAC. In March 2022, the company announced its partnership with Spain-based biopharmaceutical company Biofabri to develop, produce, and distribute MTBVAC, a novel TB vaccine. Phase 3 trial is currently underway in TB-affected regions of Sub-Saharan Africa such as South Africa, Madagascar, and Senegal. With 25% each, Sub-Saharan Africa and India account for the highest TB burden across the globe. The vaccine is being developed to target TB in these susceptible regions to eradicate the disease.

Several other Indian manufacturers have rolled out successful vaccines against various diseases in Africa that have significantly reduced the disease burden in the region.

EOS Perspective

Achieving 60% local vaccine production within 15 years will be possible only if Africa chooses a robust role model to learn from. India stands out as possibly the only near-perfect choice for that. To foster the development of a seamless and sustainable vaccine ecosystem, Africa should replicate, take guidance, and collaborate with Indian manufacturers as much as possible.

The world has evolved and many steps taken by India in the past cannot be directly transplanted into the current African scenario. However, India’s approach to building self-reliance in pharmaceutical production can undoubtedly offer valuable lessons. Direct know-how and technology transfer, collaborations, approach to talent training, production facilities management, procurement handling, supply chain management, licensing, and IP protection are critical aspects in which Africa could utilize India’s expertise and experience in vaccine making.

By choosing India as a role model and emulating its focus on nurturing a competitive pharma manufacturing industry, Africa could take a significant step towards achieving the goal of self-sufficient vaccine production.

28/06/2024by EOS Intelligence EOS Intelligence No Comments

Pet Wearables – Are Companies Barking Up the Right Technology?

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As the human wearables market begins to mature, a lot of interest and developments are also happening in the pet wearables space. An increasing number of pet owners becoming more technologically savvy has fueled product innovations in this segment, which traditionally was limited to GPS tracking. While location tracking continues to be the largest piece of the pie, other solutions, such as health monitoring devices, have been gaining prominence. However, this segment is still in its infancy and is toying with several technologies, such as biometrics, radar, and acoustic technology, to develop functional, accurate, and price-effective devices.

The last decade has witnessed exponential growth and advancements in human wearables. However, recent years have also seen the trend of wearables permeating the pet market. With upcoming technological advancements, the industry is expected to witness double-digit growth over the next six years and expand into new territories.

Read our related Perspective

Poop to Pills: Is FMT the Future of Veterinary Medicine?

ID tracking is the largest category, health monitoring is growing the fastest

The pet wearables market is primarily bifurcated into four applications: ID tracking, behavior control, safety, and health monitoring. At the moment, the largest category within the market is ID tracking solutions, which comprise GPS—and RFID-based trackers that help identify and locate pets. One of the leading players in this space is US-based Tractive, which provides a GPS collar that allows pet owners to know the exact location of their pets at all times.

The fastest-growing category is health monitoring. This segment encompasses devices that monitor a pet’s vitals and general health and raise an alarm in case of any irregularities. Growing pet obesity cases have resulted in pet owners choosing health monitoring devices for their pets. A popular product in this space is the PetPace Smart Collar by US-based pet wearable company, PetPace, which tracks physiological metrics such as pulse, respiration, temperature, heart rate variability (HRV), activity level, and posture. Along with GPS tracking and emergency alerts, it helps in early symptom detection and disease management.

The behavior control segment, which is still relatively small, covers products that help teach pets appropriate behavior, such as bark collars, which deter dogs from barking continuously. An innovative and popular product in this category includes the PetSafe Treat & Train Remote Reward Dog Trainer by US-based pet-tech company PetSafe. The product allows pet owners to dispense treats remotely through an electronic trainer to induce calm behavior in case of distracting situations, as well as allows owners to reward their pets in case of good behavior.

The smallest category is safety, which is largely an extension of ID tracking and comprises pet cameras that capture a pet’s movement. Mr. Petcam is a US-based company that provides collar-mounted HD video cameras for dogs or cats, allowing pet owners to see what their pets see in the yard, at home, or during walks.

Pet Wearables – Are Companies Barking Up the Right Technology? by EOS Intelligence

The industry is undergoing both organic and inorganic growth

Pet adoption increased significantly during the COVID-19 pandemic as people were confined to their homes and lacked social and emotional connection. As per the American Society for the Prevention of Cruelty to Animals, one in five Americans purchased or adopted a pet during COVID-19.

Many of these pet owners are adept in technology and spend vast sums of money on their pets. As pets are increasingly considered family members and with growing concerns for their health and well-being, pet wearables are experiencing a surge in popularity. The success of wearable technology for humans further fuels this trend. Moreover, increasing costs of veterinary services and treatments have propelled pet owners to invest in health and prevention-based wearables. Therefore, the industry is expected to grow significantly, especially in Europe and North America, in the coming years.

However, that being said, the industry is in its nascence and is highly fragmented at the moment. There is a large number of players fueled by several start-ups and new entrants. The industry is seeing a surge in acquisitions as players in the pet care and tech space are looking to expand their offerings to include pet wearables. Moreover, growing interest from venture capital firms is also resulting in large investments in companies showing promise in this space.

One of the leading players in the pet market, Mars Petcare, launched Companion Fund in 2018 and Companion Fund II in October 2023. The US$100 million and US$300 million venture capital funds, respectively, have been created to invest in start-ups in the pet care space, including pet wearables. Earlier, in 2016, Mars Petcare acquired the Whistle pet monitor and GPS tracker, similar to a Fitbit for dogs, for about US$117 million. This provided Mars Petcare an entry into the pet wearables space.

Several other players in the technology space have also acquired companies to expand their business to cover pet wearables. In 2019, Florida-based IoT company Smart Tracking Technologies acquired Link AKC for an undisclosed amount. This wearable pet technology company developed GPS-enabled dog collars and won the Best Innovation award at CES 2017 in the wearable technology category.

In April 2023, Ultrack, a leading global GPS tracking solutions provider, signed a contractual agreement to acquire and market Supreme Product’s wearable GPS-based Pet Tracker. The device is expected to have multiple features, such as health monitoring, behavior modification, predictive analytics, social media integration, and virtual fences.

Similarly, in May 2023, Datamars, a global data solutions company, acquired Kippy, an Italy-based GPS tracking and activity monitoring solution provider. Kippy collar’s main features include GPS tracking, customized activity monitoring and analysis, reminders and access to vet records, temperature alerts, tone and vibration training controls, a built-in flashlight, and the ability to create safe places for the pet.

While several companies are adopting the inorganic growth strategy, there is also a lot of venture capital interest, especially in ID tracking, which is the largest product category and acts as an entry point device for many customers in the pet wearables space. In 2021, Austria-based leading pet tracking company Tractive raised US$35 million Series A round (led by Guidepost Growth Equity) to expand its offerings in the USA. Similarly, in 2021, Fi, a US-based pet wearable start-up, received US$30 million in Series B funding (following a Series A funding of US$ 7 million in 2019) for its smart pet collars to expand its footprint across the USA.

Pet wearables companies seek the right tech for pet health monitoring

While most technologies used in pet wearables are fairly similar to those used in human wearables (such as GPS), one of the key differentiators is the effectiveness of biometric sensors for health monitoring. Biometric sensors are widely used in human wearables, although given the fur presence in animals, they are somewhat ineffective in the case of pets. Thus, pet wearables depend on other contactless sensors such as radar and acoustic. However, these have their own functional and developmental challenges.

Among these, acoustic sensors are some of the oldest and are used by one of the market leaders, PetPace. Acoustic technology uses sound waves to monitor a pet’s heart rate, heart rate variability (HRV), and respiratory rate. Players such as PetPace and Inupathy use this technology in their smart collars. Moreover, in 2020, the Bioengineering Department at Imperial College also developed wearable technology for sniffer dogs based on acoustic sensors.

While this technology is fairly widely used for clinically monitoring health for both humans and pets, there are certain challenges when it is translated into wearables for pets. Given external factors, such as background noise and motion artifacts, the PetPace collar is said to have only 53% heart rate detection sensitivity (i.e., in 53% of the cases, the standard deviation from measurements by PetPace and ECG was within 10%) based on a study conducted in 2020. However, based on another 2017 study, the device’s pulse monitoring accuracy levels can be much higher at 94.3%.

That being said, Tokyo-based Inupathy also uses acoustic sensors to capture a dog’s heart rate and HRV and displays colors and patterns on its pet collar to depict emotional state and heartbeat ranges. For instance, the calmest state is depicted with deep blue, whereas the most excited state is bright red. While the company claims to have 90% accuracy when compared with ECG monitors, the collar is marketed as a device to broadly understand the mental and physical state of the pet instead of accurately monitoring and projecting heart rate readings.

Thus, while acoustic technology can be used in pet wearables, it has limitations, especially regarding accuracy. With the PetPace collar being priced at about US$150 (with a monthly subscription of US$15) and Inupathy at US$200, the customer must be able to find value in the readings. One of the initial companies using acoustic sensors, Voyce, went out of business in 2016 due to slower-than-expected acceptability.

Acoustic sensors-based solutions by themselves may not be a sound product offering, however, when clubbed with other technologies and solutions, they can offer a wholesome solution to the pet owner. This can be seen in the case of PetPace Smart Collar, which, along with acoustic-based health monitoring, has additional offerings such as thermometers for temperature detection, 6-D accelerometers for activity, calories, and posture calculation, and GPS for location tracking.

A more promising and upcoming technology for health monitoring in pets is radar technology. The technology uses radio waves to enable continuous and contactless heart and respiration rate monitoring. While it is relatively new, it is expected to have better accuracy when compared with acoustic sensors. Two companies, France-based Invoxia, and Taiwan-based ITRI, launched smart collars with radar technology in 2022. Invoxia’s smart collar is priced competitively at US$99 (with a monthly subscription of US$13). It uses embedded artificial intelligence and miniaturized radar sensors to track a dog’s health. In addition, it monitors a dog’s daily activity, such as walking, running, scratching, eating or drinking, barking, and resting. The device has an accuracy of 98% for heart rate detection.

Similarly, ITRI also launched its smart wearable device, iPetWear, in 2022. The device uses contactless micro-physiological radar sensing technology to monitor a pet’s health. The sensor can monitor a pet’s heart rate, respiratory rate, sleep cycle, and activity levels through the detection of pulse and chest motion through its lower-power Doppler radar technology. The device claims to have an error rate of under 10% for heart and respiration rate and under 5% for activity monitoring. The device is priced at US$80.

Given the improved accuracies and competitive pricing of these products, it is safe to say that radar technology-based sensors can disrupt pet health monitoring wearables. However, this technology is difficult to develop, and at the moment, only a limited number of companies have managed to commercialize it.

Companies are also exploring ways to make biometric sensors effective for pets, even though furry pets present a challenge for such sensors. This is seen in the case of Invoxia, which had previously launched the radar-based Smart Collar. At CES 2024, Invoxia launched another pet wearable device, the Invoxia Minitailz Smart Pet Tracker. The tracker uses advanced miniaturized biometric sensors along with AI to track respiratory and heart vitals and detect anomalies in the behavior of both dogs and cats. In addition, it tracks a pet’s location and daily activities and can differentiate between types of movement. It also claims to be the first pet collar in the market to detect atrial fibrillation (AFib). The device also seems to have high accuracy (similar to radar technology) as it claims to have 97-99% accuracy rates for monitoring respiratory and heart vitals. The product, priced at US$99 with a monthly subscription cost of US$8.30, is relatively new in the market, and its effectiveness is yet to be established.

If Invoxia Minitailz Smart Pet Tracker is successful and delivers on its promise (with regard to accuracy and functionality), several other players will likely also explore biometric sensors for pet health monitoring.

Other technologies, such as LiDAR and infrared, are also being explored as potential alternatives. However, there are not many commercially successful solutions based on them yet.

Potential risk of data breach is one of the biggest threats to pet wearables

Given the expanding scope of all these technologies, the pet wearable market is booming. However, it comes with its own set of challenges. While companies claim to have high accuracy rates, no FDA approvals are required for pet wearables at the moment. Thus, there is no way to verify the actual effectiveness of these devices. Moreover, since they deal with critical health conditions, a missed reading or a misdiagnosis can have dire consequences. Pet owners can also not consider these devices to be a replacement for their vet visits at large, and the devices can only act as information gatherers that can help vets make quicker diagnoses.

The industry is also facing a significant obstacle in the form of substandard battery technology. Given the number of features on each device (such as GPS tracking, health monitoring, two-way communication, etc.), its continuous and real-time work requirement, and the limited lifespan of lithium-ion batteries, companies have difficulty providing sufficient battery life for their devices. In several cases, pet owners find that the battery gets discharged sooner than they can recharge it. Therefore, the device loses its purpose since it is meant to provide continuous real-time data to be effective. To mitigate this, companies are looking into other battery options, such as lead acid (less efficient than lithium-ion) and silicon carbide (a more expensive option).

Another issue with these devices is the potential risk of data breaches. Wearables collect large amounts of data about pets and pet owners. In a 2019 study by Bristol University, pet wearable devices collected four times more data about the pet owner than about the pet itself. If this data is not properly secured, it could result in data leaks and cyberattacks and put the owner at risk.

EOS Perspective

With pet ownership increasing, the market for pet wearables will undoubtedly grow. Moreover, as human wearables continue to permeate our daily lives, it is natural that pet owners are looking for a similar advanced level of monitoring for their beloved companions.

The market, which started with single functionality tracking devices, is now moving towards more complex and technologically advanced solutions. While tracking and GPS-based devices continue to form a significant portion of the market at the moment, several leading players in the space (such as Tractive) are now integrating other functionalities with their location-tracking offerings.

Thus, the market is expected to move towards multi-functional solutions that offer basic features such as tracking along with advanced features such as activity and health monitoring. Also, within health monitoring, offerings will continue to differ based on complexity. For instance, some devices offer insights only into weight and temperature changes, while more advanced devices offer heart and pulse rate monitoring. As seen in the case of human wearables, the market is likely to move towards the latter as continuous advanced health monitoring becomes a standard way of managing well-being for both humans and pets.

Given the industry’s nascence, fragmented market, lack of big established brands, and low brand loyalty, the products’ key differentiating factors are likely to remain competitive pricing, advanced offerings, and effective technology.

For this, it becomes essential for companies to stay ahead of the curve and to explore possible technologies, beyond what is effective in human wearables. Therefore, companies that are investing in exploring suitable technologies, such as radar and biometrics, for advanced features, such as heart rate monitoring, are likely to emerge as market leaders in the long run.

Moreover, the pet wearables market is likely to also benefit from integration with pet insurance in the future. Both industries have synergies as the insurance sector can gain from health-based data derived from pet wearables. On the other hand, increasing demand for pet insurance is expected to provide a push to the pet wearables market, as pet owners who track and monitor their pet’s health can negotiate better and more competitive insurance rates.

Undoubtedly, the industry is poised for steady and strong growth. The market will likely consolidate, while players offering technologically advanced wearables focused on health monitoring and priced at around US$100-150 will emerge as leaders.

20/06/2024by EOS Intelligence EOS Intelligence No Comments

IRA: Are Patients Winning at the Cost of the US Pharma Sectoral Growth?

The market reaction to the US Inflation Reduction Act of 2022 is mostly mixed. It is expected to change the pharma industry dynamics in terms of the competitive positioning and product pricing of those companies projected to be negatively impacted by the IRA. The answer to whether the IRA will be able to curb rising healthcare costs in the USA lies in the legislation’s on-the-ground application.

IRA to decrease prescription drug prices via a four-pronged strategy

Prices of prescription drugs in the USA are 2.78 times higher than in 33 other countries analyzed in a 2024 report published by RAND, a public policy think tank.

In pursuit of reducing healthcare costs in the USA, the Biden government passed the Inflation Reduction Act (IRA) in August 2022. One of the major goals of the act includes the reduction of prices of prescription drugs.

This is expected to be achieved through a four-pronged strategy, the mainstay of which involves the US federal government negotiating the prices of some high-priced prescription drugs covered under Medicare.

The second prong includes pharmaceutical firms paying a rebate to Medicare if they raise the price of prescription medicines covered under Medicare by a rate that is higher than the inflation rate.

The monthly cost of insulin for Medicare patients is capped at US$35, as the third prong.

The fourth prong aims to reduce prescription drug prices by capping the out-of-pocket costs of Medicare Part D patients at US$4,000 in 2024 and US$2,000 in 2025.

IRA Are Patients Winning at the Cost of the US Pharma Sectoral Growth by EOS Intelligence

Pharma companies to suffer more due to IRA compared to projected government savings

Under the IRA, large pharmaceutical companies, defined as those with over US$1 billion in net profits, are required to pay a minimum of 15% annual taxes, a financial burden on these companies. Analysts predict that the annual revenue from corporate taxes could be to the tune of US$222 billion. Furthermore, the IRA is expected to save over US$287 billion for ten years from the roll-out, as per the estimates of the Congressional Budget Office (CBO).

Apart from the increased financial burden on some companies, experts foresee potential adverse impact on several pharmaceutical companies based in the USA to a considerable extent.

The pharma companies witnessing the least to no impact are the ones with their primary operations based outside the USA, biologics or large molecule drug producers, and the ones that do not receive government funding for R&D. This is because of the differing timelines under IRA for negotiating the prices of biologics and small molecules. Biologics’ timeline is 11 years after FDA approval, while small molecule drugs are eligible after 7 years. Therefore, Medicare negotiations will begin four years earlier for a small molecule drug that has received approval at the same time as a large molecule biologic drug.

Apart from these adverse effects, such as differential treatment of small molecule drugs compared to biologics under Medicare price negotiation timelines, there are some other negative impacts on the overall US pharma industry, such as diminishing competition among generic drug producers, decreased discovery of new treatments, and new uses of existing drugs.

IRA to affect the revenues of top pharma companies surely but variably

There are differing viewpoints regarding the impact of IRA on pharmaceutical companies’ revenue. One group of experts suggests that Medicare prescription drug negotiations under the IRA will depend on the expiration of the drug’s patent. Other experts expressed their opinion that irrespective of when a drug loses exclusivity, a significant threat to drug revenues comes from the competition entering the market and not from lower negotiated drug prices.

The first group of experts states that lower negotiated prices in 2026 are expected to have a lower impact on medicines projected to witness revenue loss owing to patent expiry around the same time. One such example of a drug losing its exclusivity in the USA in 2025 is Stelara by Janssen Biotech approved for treating psoriasis.

In contrast, pharma companies producing medicines that are expected to witness competition from their generic counterparts after 2026 are projected to lose revenue owing to lower negotiated prices even before the drugs lose exclusivity. However, some companies’ revenue will be affected more than others.

Medicare price negotiations to hit revenues of some drugmakers drastically

The pharma industry’s revenue is expected to decrease by 2% due to the new measures brought about by the IRA, as per a 2022 report by Morningstar, a US financial services firm. Among the companies that will be highly affected are Novo Nordisk, Gilead, Bristol Myers Squibb, AbbVie, and AstraZeneca. In contrast, others, such as Pfizer, Merck, Roche, and Novartis, will not be as much impacted by Medicare price negotiations.

Some 15% of global branded drug sales come from Medicare in the USA, as per Morningstar estimates. Therefore, the impact of the IRA on pharmaceutical companies depends on their reliance on Medicare sales, price adjustments, high-cost specialized drugs, and extended patent protection.

Medicare prescription drug negotiations are projected to impact pharma companies the most among all IRA measures, although this impact might not be uniform across the players. On the other hand, Medicare negotiations are projected to save the government approximately US$100 billion through 2031. The pharma companies facing the highest revenue losses include Novo Nordisk, Gilead, and AstraZeneca.

When the Medicare price negotiation measures start to roll out in 2026, two drugs of Novo Nordisk, namely, Ozempic and Rybelsus, that are approved to treat type 2 diabetes, are expected to witness an 8% decline in their projected revenue through 2031, as per Morningstar. Gilead’s Biktarvy, which treats HIV-1 infections, is expected to be subject to price negotiation in 2027 and thereby face a projected revenue loss of 7% through 2031. On similar lines, Calquence (to treat mantle cell lymphoma) and Tagrisso (to treat non-small cell lung cancer) drugs of AstraZeneca are expected to lose 6% revenues through 2031 owing to Medicare price negotiations.

In contrast, considering the existing portfolios, Pfizer, Merck, Bristol Myers, and BioMarin are expected to witness no revenue loss due to Medicare negotiations.

Medicare inflation caps to impact major pharma companies negatively

Another important IRA measure is Medicare inflation caps. This measure involves drug producers paying penalties for increasing drug prices beyond the inflation rate. It is expected to result in US$62 billion in government savings through 2031.

Around March 2023, the US federal government, along with the Centers for Medicare & Medicaid Services (CMS), released a list of 27 drugs whose prices were increased by their manufacturers at a higher rate than the inflation rate. This list included AbbVie’s Humira (to treat Crohn’s Disease) and Astellas Pharma’s and Seagen’s Padcev (to treat urothelial cancer). Gilead Sciences, Johnson & Johnson, and Pfizer are among other impacted companies by Medicare inflation caps. Pfizer had the most drugs on the list, with a total of five.

Bristol Myers Squibb is one of the pharma companies that is expected to be highly impacted by Medicare inflation caps. The company’s drugs, such as Eliquis (to treat or prevent blood clots), Opdivo (to treat melanoma), Orencia (to treat rheumatoid arthritis), and Yervoy (to treat various cancer types) are among the medicines that are expected to face revenue loss owing to inflation caps. Other drugs on the list include Novo Nordisk’s drugs such as Novolog and Levemir (both for type 1 diabetes) and Victoza (for type 2 diabetes), Johnson & Johnson’s drugs such as Imbruvica (to treat certain cancers) and Xarelto (to treat or prevent blood clots), along with Novartis’s Sandostatin (for severe diarrhea and flushing related to metastatic carcinoid tumors).

In contrast, Merck is not expected to face any revenue loss due to inflation caps, while GSK, Regeneron, Roche, and Sanofi are projected to witness minimal revenue loss as these companies have not raised the prices of their drugs beyond the inflation rate.

IRA to potentially reduce competition from generics

According to the IRA, following the price negotiations of some of the branded drugs, manufacturers of the generic versions of such drugs will have less scope to charge a reduced price for those drugs. This would disincentivize the generic drug producers to manufacture generic versions of the already low-priced branded drugs.

EOS Perspective

The IRA represents a substantial change in the US legislation that strives to make healthcare more affordable to Americans through increased access to more reasonably priced prescription medicines.

However, IRA can be expected to affect small-molecule drugmakers more negatively than biologics. Moreover, some pharmaceutical companies are projected to feel the pinch more than others in terms of revenue losses.

Companies such as Merck, Bristol Myers Squibb, and the pharmaceutical association PhRMA have filed lawsuits against some provisions of the IRA, stating that they are unconstitutional. Bristol Myers Squibb and J&J are planning to appeal after the US court dismissed the IRA lawsuits. These pharmaceutical companies are trying to find ways to circumvent the negative impact of the legislation.

IRA is also expected to negatively impact R&D and medical innovation. This is evident from the fact that biopharma companies have reduced their R&D efforts in the neuroscience space, especially since a lot of development work in this space involves small-molecule drugs. Moreover, as IRA exempts only one orphan drug from price negotiation, investments in R&D for orphan drugs are likely to get deprioritized. Many pharmaceutical companies are reconsidering their R&D planning and investment strategies to counter the effect of IRA.

IRA is clearly not a win-win strategy for all stakeholders. Pharmaceutical companies are mostly at the losing end, while patients could be winners. Considering all the positives and negatives of IRA, only time will tell the actual impact of the legislation on the overall pharmaceutical industry.

30/05/2024by EOS Intelligence EOS Intelligence No Comments

An Era of Innovation: Novel Drugs Redefining Multiple Sclerosis Treatment Paradigm

Since the approval of the first drug, interferon beta 1b (IFNβ-1b), in 1993, the treatment landscape of multiple sclerosis (MS) has significantly changed. Currently, there exist more than 20 disease-modifying therapies (DMTs) to treat MS, encompassing orals, injectables, and infusions. These drugs, however, can cause adverse side effects such as toxicity, pregnancy-related complications, and gastrointestinal symptoms, among others. Moreover, about 5-10% of the patient population still develops disability. Despite the wide range of therapeutic options available, patients experience relapses and worsening disease symptoms, which significantly reduce their quality of life.

The ongoing challenges have driven pharmaceutical companies to develop and launch drugs that offer greater efficacy and safety, enhancing patients’ health outcomes in the longer term. In particular, significant efforts are geared towards treating the progressive forms of MS, such as Primary Progressive MS (PPMS) and Secondary Progressive MS (SPMS), for which therapies are currently limited.

Several emerging therapies are in various stages of development, targeting distinct mechanisms of the underlying disease etiology. Among all the emerging therapeutic approaches, Bruton Tyrosine Kinase Inhibitors (BTKIs) emerge as the most promising, currently in later stages of clinical trials, poised for approval. The potential advantage of BTKI agents is that they can treat both relapsing and progressive forms of MS.

Remyelination is another equally promising therapeutic approach, as it has the potential to promote myelination, restore axonal and neuronal health, and prevent disability; however, extensive clinical trials are essential to develop these drugs and fully integrate them into clinical practice.

On the other hand, monoclonal antibodies (mAbs) are becoming the most common therapeutic option due to their higher selectivity for B-cells (a type of immune cell), a fact that plays a crucial role in MS disease pathogenesis. The higher selectivity of mAbs allows to efficiently target these cells and reduce inflammation.

An Era of Innovation Novel Drugs Redefining Multiple Sclerosis Treatment Paradigm by EOS Intelligence

Pharma companies place high hopes on BTKI

Following the success of B-cell depleting therapies in treating MS, there has been a notable surge in interest in utilizing a novel class of medications called BTKI. BTK is an enzyme crucial for the functioning of B-lymphocytes, which elucidates the autoimmune response in MS patients. Unlike B-cell depleting therapies, which directly reduce the number of B-cells, BTKIs alter B-cell function, preventing relapse or slowing disease progression in MS patients.

These BTKIs can be taken orally, offering a convenient and easy way of administration. Another potential advantage is that BTKIs can cross the complex blood-brain barrier, which other MS drugs fail to do. Due to this potent efficacy, researchers believe that BTK inhibition can even act as a cure for MS.

Over the past few years, top pharma companies such as Roche, Sanofi, InnoCare, and Novartis have betted big on BTKI to treat MS patients. There are currently four BTKI agents that are being investigated for MS treatment – Sanofi’s Tolebrutinib, Roche’s Fenebrutinib, Novartis’ Remibrutinib, and InnoCare’s Orelabrutinib. Among these, Sanofi is ahead in the race, looking to submit its BTKI drug Tolebrutinib to treat Relapsing-Remitting Multiple Sclerosis (RRMS) for FDA approval in 2024. The company is also currently evaluating Tolebrutinib in a phase 3 trial for treating PPMS, which is expected to be completed in August 2024. If successful, Sanofi would become the first pharmaceutical company to offer BTKIs for both RRMS and PPMS. At present, Roche’s Ocrevus (Ocrelizumab) is the only DMT approved for treating PPMS. Sanofi’s approval of BTKIs would set the stage for direct competition between Roche and Sanofi in the treatment of PPMS. However, Roche’s Ocrevus patent expires in 2029, hence the company remains focused on its BTKI drug Fenebrutinib.

Similar to Sanofi, Roche is testing Fenebrutinib for treating both RRMS and PPMS patients. Roche is slated to complete its phase 3 studies investigating the drug to treat RRMS in November 2025 and PPMS in December 2026.

Novartis and InnoCare are slightly trailing in the competition. Novartis is currently evaluating its BTKI drug, Remibrutinib, in phase 3 clinical trials to treat people with RRMS, expected to be completed in 2029. On the other hand, InnoCare is currently evaluating Orelabrutinib in phase 2 trials for RRMS treatment. Both Remibrutinib and Orelabrutinib cannot be used to treat PPMS, which is a major limitation.

The development of BTKI fosters hope for the next era of MS treatment, as the therapy treats both relapsing and progressive MS. However, the safety and efficacy of each drug still needs to be understood.

Results from BTKI clinical trials indicate that these drugs differ in the strength of BTKI inhibition, BTK enzyme binding mechanism, and central nervous system (CNS) penetration. For instance, Sanofi’s Tolebrutinib showed greater CNS penetrance than the other BTKI agents, making the drug a potential candidate for treating PPMS. On the other hand, Roche’s Fenebrutinib is the only reversible BTK inhibitor that does not cause drug resistance, thus offering a better and safer treatment compared to the rest of the BTKI agents.

It is too early to predict the timeline and extent to which these drugs will be incorporated into the MS treatment paradigm. Until then, pharmaceutical companies in this space will persist in vying to accelerate the launch of their therapies in the fiercely competitive MS market.

Therapies targeting remyelination nearing clinical trials

In MS, myelin, a fatty tissue that surrounds the nerve cells, gets damaged, impairing the nerve’s ability to send electrical signals. At present, no therapies can promote myelin repair in MS patients. The current treatments focus primarily on reducing immune system activity and stopping immune cells from entering the CNS to reduce relapse rates and improve symptoms. The emergence of remyelination therapies holds extensive promise by protecting and restoring neuronal function, and preventing clinical disability in MS patients.

Remyelination works by either removing myelin debris or by creating a type of cells called oligodendrocytes to repair and replace the damaged myelin sheaths.

Over the last few years, pharmaceutical companies have shown heightened interest in evaluating and developing drugs that could promote remyelination. Some of these drugs are in later stages of development, nearing clinical trials.

For instance, in March 2024, Convelo Therapeutics, a US-based biotechnology company, announced that its two oral therapies showed promising evidence in myelin repair in animal models. Similarly, in the same month, the FDA granted a breakthrough device designation to a neurostimulator, for treating RRMS. The device is developed by SetPoint Medical, a US-based healthcare company, to slow myelin damage in RRMS patients. Both these companies have been working to begin clinical trials soon to test their remyelinating agents.

Numerous other companies across the world are also conducting extensive research on remyelination therapies for MS. Additionally, studies are underway to explore the potential of existing drugs, such as Metformin, Ibudilast, and Clemastine, among others, in promoting myelin repair. Encouraging results from preclinical trials and ongoing research studies foster growing optimism that this approach will become viable in treating MS patients in the future.

However, work on remyelination to treat MS patients has just begun, and there is still a long way to go. Defining the optimal clinical criteria for evaluating myelin repair appears largely undefined. There is also an urgent need to develop tools to measure the remyelination achieved and assess the drug’s effectiveness. That said, recent discoveries shedding light on remyelination processes and the functions of oligodendrocyte cells inspire hope that these issues will be effectively addressed in the coming years. Companies are also developing advanced imaging techniques to quantify myelination.

Overall, remyelination emerges as the sole therapy focused on repairing the neuro damage and improving the neurodegenerative conditions in MS patients, which is not currently fulfilled by existing treatments. This underscores remyelination as an inevitable treatment approach for both RRMS and PPMS.

Monoclonal antibodies continually transforming the MS treatment landscape

In recent years, mAbs have emerged as the indispensable treatment option for managing the relapsing forms of MS. These therapeutic agents offer high efficacy in managing symptoms while providing additional advantages such as ease of dosing and lower side effects compared to traditional therapies.

Given the promising potential of this therapeutic approach, pharma companies strive to introduce novel mAbs targeting different cells, molecular pathways, or molecules. Interestingly, new mAbs are also being developed to help repair the damage or disability that has already occurred. Thus, mAbs aim not only to alleviate symptoms but also repair the damage caused by MS, potentially reversing disability – a critical unmet need in the MS treatment landscape.

Among all the mAbs approved, antibodies that target the CD20 molecule (a protein found on the surface of B-cells) have gained significant interest lately. In recent years, the FDA has approved various therapies targeting anti-CD20 molecule. Currently, anti-CD20 mAbs such as Ocrelizumab, Natalizumab, Ofatumumab, Ublituximab, and Rituximab are used for the treatment of MS. Ocrelizumab, developed by Roche, stands out as the only mAb approved for treating both RRMS and PPMS. Ublituximab, developed by TG Therapeutics, is the latest addition to this group, approved by the FDA in 2022.

The mAb market is highly competitive. Hence, companies have been increasingly seeking to differentiate their products based on parameters such as efficacy, safety, and dosing convenience to capture larger market shares. For instance, Novartis considers the ease of administration to be the primary differentiating factor to help drive its mAb sales. The company launched Ofatumumab in 2020, the only mAb that can be administered via injection for treating RRMS. Similarly, Roche is developing Ocrevus subcutaneous injection version similar to the IV infusion. Phase 3 trials are currently underway to evaluate the drug to treat both RRMS and PPMS.

Companies have also been looking to differentiate their drugs in terms of safety. The common side effect of MS therapies is lymphopenia, i.e., lymphocyte depletion, which can pose risks, such as increased vulnerability to infections. To address this, Sanofi is developing a CD40-based mAb named Frexalimab to treat RRMS and SPMS. CD40L is a protein that activates the innate and adaptive immune systems in humans. Sanofi’s phase 2 trials investigating Frexalimab rapidly reduced the disease activity up to 89% without depleting the lymphocytes, thus offering a safer treatment option. Sanofi already has a strong MS pipeline with its BTK drug, Tolebrutinib, to be approved in 2024. Frexalimab, once approved, is expected to further boost the company’s market share.

While mAbs are promising, factors such as high prices hinder their market penetration. Consequently, companies have been looking to develop biosimilar compounds for mAbs, aiming to lower drug prices while simultaneously maintaining and expanding their market share. For instance, in August 2023, the FDA approved Tyruko, a monoclonal antibody that is a biosimilar version of Biogen’s Natalizumab, for treating RRMS. Overall, an increased interest in R&D, coupled with the number of clinical trials underway indicate that mAbs will remain a favored approach in MS treatment for the foreseeable future.

EOS Perspective

The MS treatment market is expected to witness significant growth, reaching a value of US$39 billion by 2032. The increasing prevalence of MS and the demand for highly effective therapies are driving pharma companies to investigate and develop novel drugs. Extensive R&D efforts and the high unmet needs for treating PPMS and SPMS are the other key factors fueling market growth. In addition, governments worldwide are actively supporting drug research with substantial funding.

To gain higher market shares in the competitive MS market, pharma companies are fiercely focusing on innovation and differentiation. They are conducting extensive clinical trials to demonstrate their drugs’ efficacy and superiority. Additionally, these companies are striving to innovate in other aspects, such as drug safety, tolerability, ease of dosing, and convenient routes of administration.

The primary challenge slowing market growth is the high cost of drugs. MS drugs are very expensive, with prices consistently rising each year. According to a 2019 survey published by the National Multiple Sclerosis Society, 40% of respondents terminated their treatment due to the high costs of DMTs. Hence, companies must navigate reimbursement processes and negotiate drug prices with payers to ensure broad patient access and increased market penetration.

Other challenges inhibiting the market growth include patent expiration and the complex nature of MS. Patent expiration allows low-priced generics to enter the market, negatively impacting drug sales. Additionally, the disease’s high heterogeneity limits companies’ ability to develop therapies for the long term.

However, despite these challenges, the MS treatment market looks promising and is continually evolving. In recent years, the treatment landscape has shifted towards introducing highly efficient and safer therapies earlier in the disease course to prevent complications in the longer term. Consequently, companies demonstrating higher drug efficacy are expected to gain a significant foothold in the market. In addition, substantial opportunities exist for companies that address neuroprotection, as the majority of the existing treatments primarily target the inflammatory part of the disease.

14/05/2024by EOS Intelligence EOS Intelligence No Comments

Gut Matter: Will FMT Change How We Look at Disease Treatments?

Converting poop to pills was something unimaginable a few years ago, but now Fecal Microbiota Transplant (FMT) is taking the medical world by storm. This revolutionary technique, which promises to treat a wide range of diseases, from GI disorders to mental health issues, is becoming popular due to its success in treating recurrent clostridioides difficile infection (CDI), a serious infection that can damage the colon. FMT offers tremendous opportunities but also has challenges that players should consider if they want to thrive in this industry.

FMT is a procedure in which feces from a screened, healthy donor are transplanted into a recipient to balance the gut microbiota. This procedure can help treat certain infections and lessen the severity of some gut health issues.

Gut infections are usually treated using antibiotics, which can occasionally destroy beneficial bacteria. A 2000 study published in the Journal of Microbiology, a delayed open-access journal of the American Society for Microbiology, indicated that CDI recurring in around 15% to 35% of people is caused by antibiotics disrupting the gut microbiota and its balance (gut dysbiosis). Dysbiosis has been linked to several chronic illnesses, such as cardiovascular disease, inflammatory bowel disease (IBD), diabetes, and colorectal cancer (CRC).

FMT is highly efficient in treating recurrent CDI, with a cure rate of 90%, according to a 2015 study published in the American Journal of Gastroenterology. Numerous trials to understand the efficacy of FMT in treating conditions such as obesity, liver disease, ulcerative colitis, Crohn’s disease, Parkinson’s disease (PD), and IBS are underway. There are also some pre-clinical studies in progress to understand the potential of FMT in treating illnesses such as diabetes, skin issues, lung diseases, and autism.

This article is the second in EOS Perspectives' coverage 
of Fecal Microbiota Transplantation in animals and humans.

Read our related Perspective:
 Poop to Pills: Is FMT the Future of Veterinary Medicine?

FMT is showing promising growth

The human FMT sector is expected to grow at a CAGR of 5.1% and reach US$3.15 billion by 2031, according to a 2023 report published by India-based market research company The Brainy Insights.

The key factor influencing this growth is the rising incidence of GI disorders. According to the GI Alliance, a US-based network of gastroenterology providers, around 20 million Americans have chronic digestive disorders. Similarly, the CDC estimates that there are around 500,000 cases of CDI reported annually in the USA, and about 9% of elderly patients die within a month of contracting healthcare-associated CDI. All these have influenced the growth of FMT, which offers a promising solution to several conditions.

Other factors influencing the FMT sector growth are the rising patient awareness and interest in preventive healthcare and the emergence of effective probiotic strains.

There are several biotechnology companies currently involved in R&D and product development. Australia-based BiomeBank became the first company to get approval from a competent authority to market its FMT-based CDI solution called Biomictra Faecal Microbiota (colonoscopic, enema, and upper GI delivery) in November 2022. This was followed by the FDA approval of US-based Rebiotix-Ferring Pharmaceuticals’ REBYOTA (rectally administered) in the same month. Seres Therapeutics, a US-based company, has also received FDA approval for its orally delivered product Vowst (SER-109) for treating CDI in April 2023. Following Seres’ footsteps, Rebiotix-Ferring is now conducting trials to develop an oral alternative, RVX7455.

US-based Finch Therapeutics is another major company developing solutions presently undergoing phase-3 studies for diseases such as chronic hepatitis B and autism. Its solution, CP101, for treating CDI, has been discontinued.

Gut Matter Will FMT Change How We Look at Disease Treatments by EOS Intelligence

The FMT sector is grappling with a multitude of pressing challenges

The FMT sector has the potential to treat numerous GI and other related disorders effectively. However, the business landscape is still marred by several challenges that players must consider.

Lack of consensus about policies is making development challenging

Regulatory hurdles are one major roadblock players face. The FDA currently regulates FMT as an unapproved biologic medicine. There is a lack of uniform guidelines for FMT, causing variations in processes, such as donor screening and processing.

The FDA took its first step toward FMT regulation in 2013. It released a set of guidelines removing the need for investigational new drug (IND) applications when FMT is used for treating CDI unresponsive to standard treatments if medical practitioners secure informed consent. However, this application is needed when FMT is used for other reasons, including safety studies.

The FDA drafted new guidance in 2016, which was finalized in November 2022. In this guidance, the FMTs acquired from stool banks are exempt from regulatory discretion. Also, the IND requirements will be waived if some conditions are fulfilled, such as getting informed consent from patients or authorized representatives and screening and testing stool under the supervision of competent healthcare professionals. There should also be no known potentially serious safety concerns, such as issues with improper handling or storage, or issues with administering product collection without the proper testing or screening. All these increase the procedural burden for healthcare practitioners. However, the FDA has indicated no regulatory policies for stool banks to reduce the administrative burden of private practice settings without the support of research staff.

Due to the significant variation in gut microbial composition among samples, FMT fails to satisfy EU drug classification requirements. Also, since human cells are not an active component of fecal matter, FMT is not covered by EU Directive 2004/23, which deals with the safety and quality of human tissues and cells. Therefore, the European Medicines Agency (EMA) has authorized the member states to regulate FMT however they see fit.

This lack of consensus has led to diverging regulatory policies, causing uncertainties for interested players and making developmental activities challenging, particularly in Europe. But despite this, many companies, such as Rebiotix-Ferring Pharmaceuticals, are making leaps in R&D.

Donor selection has social, ethical, and financial challenges

Another bottleneck that needs to be addressed is the availability and selection of suitable donors. There is a debate regarding whether the patient should know the donor or not. Also, the ideal donor should be free from chronic illnesses or infections and willing to donate. The donor is screened for obesity, antibiotic resistance, microbiome diversity, oncogenic potential, a history of antibiotic use, and risky behaviors such as drug abuse.

Stool banks require donors to follow several restrictions, such as maintaining BMI, abstaining from unhealthy eating habits such as spicy foods or saturated fatty acids, and avoiding travel to infection-prone tropical regions for an extended period. With that, donor dropout is high due to the considerable commitment needed, according to a 2019 study published in Gastroenterology, the official journal of the American Gastroenterological Association (AGA).

FMT implementation is also facing several social and ethical challenges with questions such as donor compensation, gender of the donor, donor and patient vulnerability, and commercial use of fecal matter.

Companies can launch educational drives targeted at patients and ideal donors to raise their awareness about FMT, tackle social resistance towards the procedure, and build trust with prospective donor candidates and patients. This can help reduce people’s reluctance to participate in FMT procedures.

The procedure remains risky, especially for vulnerable population

FMT is associated with an increased risk of transmitting infections such as Shiga toxin-producing E. coli (STEC) and enteropathogenic E. coli (EPEC) from the donor to the receiver. Immunocompromised patients are at a higher risk of developing side effects, according to a 2020 study published in Digestive Diseases and Sciences, a peer-reviewed journal. Similarly, a 2019 case study published in the New England Journal of Medicine, a journal of the Massachusetts Medical Society, showed a fatal infection contracted by an elderly immunocompromised individual following an FMT procedure.

Another challenge is the very few pediatric clinical trials, which makes it difficult for physicians to make the best judgments for when to initiate FMT therapy in children.

To tackle safety-related challenges, the FDA released safety advice in 2019 and 2020 regarding the possible risk of severe, potentially fatal infections associated with the procedure. Companies such as Boston-based OpenBiome have promptly modified their sample screening methodology to identify such infections.

Lack of studies on long-term effects

The lack of understanding of the long-term changes FMT can cause in a patient’s microbiota is another challenge. Several studies reveal that liver diseases, cancer, cardiovascular diseases, etc., can develop due to microbiota dysbiosis. Investment in R&D by interested and capable players can help medical professionals understand the long-term implications and complications of FMT and identify feasible solutions, which can pave the way for widespread treatment acceptance.

The sector’s future appears bright, underpinned by extensive development

FMT is a highly effective treatment for recurrent CDI. New developments have been taking place in many areas, such as administration modes, stool collection, and storage, and interested players can find opportunities in these areas. The FDA is also becoming more accepting of FMT-based treatments that show good results. This is shown by the approval of Rebyota and Vowst, both of which were more effective in reducing recurrent CDI compared to placebo in randomized controlled trials.

Stool banking and processing is another area ripe with opportunities for interested players. Conventionally, fresh stool is used for FMT, but this can increase the cost of the procedure. Stool banks are being developed to facilitate cost-effective and safe treatment. An example is OpenBiome, the USA’s first and biggest public stool bank. Stool banks can also make the standardization of stool processing and donor selection easier, according to a 2019 report published by the European Helicobacter and Microbiota Study Group.

Players can also form collaborations with healthcare professionals and research institutions to offer FMT treatments and support microbiome research. Many government organizations are also showing interest in the development of FMT therapies. The GBP500,000 grant awarded by the Biotechnology and Biological Sciences Research Council (BBSRC), a part of UK Research and Innovation, in 2022 to Norwich-based Quadram Institute (QI) to build and equip a new FMT research facility is an indication of this.

Investing in the development of FMT treatments can revolutionize the treatment of several diseases, and companies that can invest in research can gain a head start in the competition. Rigorous R&D is going on to develop FMT solutions for conditions such as obesity, depression, cancer, pediatric diseases, and autoimmune disorders such as Crohn’s disease.

A 2023 trial conducted by the US-based Emory University School of Medicine also showed that FMT can reduce the colonization of multidrug-resistant organisms in kidney transplant patients. Investigators believe more research in this field can help improve transplant success rates and decrease the chances of infection. Individual case studies have shown great improvement in cure rates for certain diseases, including mental health conditions, but more research is needed to present a solid case for product development.

EOS Perspective

FMT is gradually establishing itself as a promising solution for recurrent CDI and is expected to create waves in the treatment of numerous physical and mental health conditions despite facing several challenges.

Improvements in donor selection, early identification of certain conditions with better risk assessment, and increased treatment efficiency can be expected with ongoing research expanding the knowledge base of the medical community.

Experts are also looking into FMT’s potential as an adjunct therapy in treating diseases such as tuberculosis, and it is expected to open the door to interested players to create personalized and targeted FMT-based treatments for various diseases.

Studies are also being done to understand and substantiate the potential of gut microbiota to anticipate diseases such as IBD and CRC using AI (Artificial Intelligence) and ML (Machine Learning). ML can be used to identify biomarkers in the gut microbiota to aid in the early detection of CRC. These studies, when extended to FMT, are expected to help medical professionals identify ideal donors and improve treatment efficiency.

The Brainy Insights, in its 2023 report, predicts a growth in the probiotic infusion segment owing to the increasing studies on diabetes management. Therefore, competitive players interested in FMT can also diversify their portfolios by including consortia (multi-population systems with a broad spectrum of microbial species) and probiotic products that have the potential to offer regulated, standardized treatments. This can help them get an edge over their competitors.

Several oral FMT solutions are currently in phase-1 and phase-2 clinical trials, and many are geared toward treating conditions other than recurrent CDI. For example, US-based Vedanta Biosciences is developing FMT therapeutics for IBD, food allergies, solid tumors, etc. As research continues, it is expected that investigators will be able to identify the bacterial strains that can treat different diseases and isolate and mass-produce them, leading to a decrease in stool collection and processing and a reduction in stool transplant-related infections, but this development is expected to occur very far in the future.

Although marred by several challenges, FMT is well-positioned in the microbiome industry to obtain FDA approval and (with time) widespread acceptance. Right now, interested players can expect good returns by investing in oral FMT development, stool banking, and R&D.

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