PFIZER 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.

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.

16/04/2024by EOS Intelligence EOS Intelligence No Comments

Anti-Obesity Drugs – Pharma Companies Race to Grab a Bite of the Pie

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For many years, bariatric surgery has been the go-to option for people struggling with obesity and obesity-induced conditions. However, for the last couple of years, another easier option has become available in the form of GLP-1-based weight loss drugs. This class of medicine mimics a hormone that helps reduce food intake and control appetite. These drugs have revolutionized the weight loss market, which was previously dominated by gimmicky and fad-based OTC solutions. Due to GLP-1’s proven effectiveness, there is soaring demand for these drugs, outstripping its current supply capacity. While only two players operate in this market, several leading drugmakers have been racing to develop their own version of the drug. Moreover, with additional proven merits of the drug beyond just weight loss, it has become more appealing for pharma players to invest in.

GLP-1 anti-obesity drugs make big waves in the pharmaceutical sector

Over the past few years, anti-obesity drugs have received immense attention from healthcare professionals, pharmaceutical companies, and the general public. A new class of medication that stands out is glucagon-like peptide-1 (GLP-1) agonists, traditionally used for treating Type 2 diabetes. But along with managing diabetes, these drugs also suppress appetite and lower calorie intake by mimicking the GLP-1 hormone (a gastrointestinal hormone), which causes the patient to feel fuller longer and thereby prevents overconsumption. Regular intake of such drugs is deemed to result in a weight loss of about 15-25% of body weight in obese people.

GLP-1 agonists received FDA approval as anti-obesity drugs in 2021. Given their promising results, the demand for these drugs has increased immensely. However, despite the patient’s high out-of-pocket price of US$1,000 plus, there are severe shortages in the market.

Anti-Obesity Drugs – Pharma Companies Race to Grab a Bite of the Pie by EOS Intelligence

Only two players operate in this highly-coveted market

The GLP-1-based medication is now marketed in two categories – one for managing diabetes and blood sugar levels and the other as a weight loss drug. The GLP-1-based weight loss drug market is highly consolidated, as only two players operate in this space. These are Denmark-based Novo Nordisk and US-based Eli Lilly.

Novo Nordisk, the market leader, received FDA approval for its weight loss injectable, Wegovy, in June 2021. This drug uses the same active ingredient as Novo Nordisk’s diabetes drugs, Ozempic and Rybelsus (oral); however, it has a different dosage and can also be used for weight loss in patients who do not have diabetes. That being said, Ozempic has also been used off-label for weight loss.

On the other hand, Eli Lilly’s injectable drug for weight loss, Zepbound, received FDA approval in November 2023. Eli Lilly’s glucose-dependent insulinotropic polypeptide – GIP/GLP-1 injectable drug for diabetes, Mounjaro, has the same composition and dosage as Zepbound and is often prescribed off-label for weight loss as well.

While Novo Nordisk’s drugs, which use semaglutide as an active ingredient, result in weight loss of about 13 to 22 lbs, the drugs by Eli Lilly have tirzepatide as an active ingredient. They are stated to result in a weight loss ranging between 15 and 28 lbs.

From a price-point perspective, Wegovy has an out-of-pocket cost of US$1,349 per month, compared to Zepbound, which has an out-of-pocket cost of US$1,060 per month. Thus, while Novo Nordisk’s Wegovy has the first-mover advantage, Eli Lilly’s Zepbound is considered more effective and better priced.

Currently, both weight loss drugs by Novo Nordisk and Eli Lilly come in the form of injectables. However, both companies are developing oral versions of the drug as they are easier to administer and more convenient to prescribe. They may also help ease supply constraints currently impacting the injectables. In June 2023, Novo Nordisk conducted Phase 3 trials for its once-daily oral Wegovy drug, according to which the drug helped obese adults lose about 15% of their body weight. Similarly, in June 2023, Eli Lilly conducted Phase 2 trials for its oral GLP-1 receptor for weight loss. The drug helped obese adults lose up to 14.7% of their body weight. Both companies are optimistic about the outcomes of their trials; however, the expected launch timelines for these drugs have yet to be determined.

Leading drugmakers race to compete in the growing anti-obesity drug market

Currently, Novo Nordisk and Eli Lilly are the only two players operating in this market. However, several other leading pharmaceutical players have joined the race and are working towards developing their own version of the drug, either through in-house R&D or through strategic acquisitions.

Moreover, they are targeting their research towards developing and marketing a new generation of GLP-1-based medications that are administered orally, are longer lasting, and have additional health benefits and limited side effects.

In February 2024, US-based biopharmaceutical company Amgen successfully completed a Phase 1 clinical trial for its GLP-1 agonist drug, MariTide. As per the trials, the drug produced a 14.5% weight loss in patients administered the highest dose. Moreover, the company claims that the trial indicates that patients may need to take less frequent doses of MariTide (compared with current competition), and the weight loss achieved stays significantly longer. The company has begun its Phase 2 trial, with results expected by late 2024.

In December 2023, Swiss-pharmaceutical giant Roche acquired US-based Carmot for US$3.1 billion (US$2.7 billion upfront cash and US$400 million on certain milestones). This acquisition has helped put Roche on the map for obesity drug development. Carmot has two GLP-1 agonist molecules for weight loss, which are currently being tested in the mid to advanced stages of clinical trials. The first drug, CT-388, is a once-weekly injectable and has completed Phase 1 clinical trial, while the other drug, CT-996, is an oral drug currently undergoing Phase 1 trials.

In November 2023, UK drugmaker AstraZeneca entered into an agreement with Shanghai-based Eccogene, wherein the former licensed an oral once-daily GLP-1 receptor agonist called ECC5004 for the treatment of obesity, Type 2 diabetes, and other cardiometabolic conditions. For this, AstraZeneca agreed to pay Eccogene an upfront fee of US$185 million for the drug and a further payment of US$1.83 billion in future clinical, regulatory, and commercial milestones and tiered royalties. The drug is currently in Phase 1 development, and the company hopes to enter Phase 2 of clinical studies by the end of 2024. In the past, AstraZeneca stopped the development of two GLP-1 agonist drugs that were being developed in-house. The development of an injectable called Cotadutide was halted in April 2023, and an oral drug called AZD0186 was halted in June 2023 after their respective Phase 2b and Phase 1 clinical trials did not yield the desired results.

Pfizer, one of the most active companies in this regard, has faced multiple failures in their endeavor to develop a competitive obesity drug. In 2020, it started a clinical trial for its GLP-1 agonist weight loss drug, Lotiglipron. However, in June 2023, the company stopped developing the drug after its Phase 1 and Phase 2 drug interaction studies indicated a rise in liver enzymes in patients who took the drug once a day. In 2021, the company simultaneously began working on another GLP-1 receptor agonist, Danuglipron, which was to be taken twice daily. While the Phase 2a trial for the drug in June 2023 showed promise, the company halted the development of the drug post its Phase 2b trial in December 2023. The drug was scrapped as, despite significant weight loss, the trial patients experienced high rates of common gastrointestinal and mechanism-based adverse side effects. The company is now conducting a pharmacokinetic study with a once-daily version of the Danuglipron drug that will provide guidance on future development plans.

Pfizer’s failure with these two drugs demonstrates the struggle the leading pharma companies face to develop a safe, effective, and tolerable GLP-1 agonist for weight loss.

GLP-1 agonist drugs have benefits beyond diabetes and weight loss

Despite multiple setbacks, leading pharma companies are investing heavily in this space, as they understand the potential of these drugs. While currently, GLP-1 agonists are poised as diabetes and weight loss drugs, they have far more benefits. Data from ongoing clinical trials and independent studies suggest that GLP-1 agonists also help improve cardiovascular health and kidney function and help treat addiction and dementia.

In March 2024, Novo Nordisk’s Wegovy received FDA approval for reducing the risk of serious cardiovascular complications in adults with obesity and heart disease. This is based on the results shared from the company’s three-phase trial SELECT, which indicated that Wegovy reduced patients’ risk of major cardiovascular problems by about 20% during the five-year trial period.

Similarly, in 2019, the company started another clinical trial, FLOW, to determine the impact of GLP-1 agonists on kidney function. As per the interim results in October 2023, the trial displayed that Ozempic (Wegovy’s diabetes counterpart) reduced the risk of kidney disease progression and kidney and cardiovascular death in diabetes patients by 24%. Given its success, the company has halted the trial at the interim stage.

An initial study conducted on animals in March 2023 reportedly showed positive results for curbing addictive tendencies, such as drinking and smoking, with Ozempic. Currently, two trials are being undertaken to validate the use of GLP-1 agonists in humans to manage drug and alcohol addiction. Given the testimonies from current users of the drug, it is indicative that the drug has been helping users curb their addictions.

In addition to this, several researchers are also suggesting that GLP-1 could be used in the treatment of dementia and other cognitive disorders. This is based on the claim that GLP-1 agonists reduce the build-up of two proteins, amyloid, and tau, in the brain. These two proteins are known to be responsible for Alzheimer’s disease, which is the most common form of dementia. In February 2022, a new trial at the University of Oxford was initiated to test people with high levels of amyloid and tau and at risk of developing dementia to determine if the use of GLP-1 agonists would result in a reduction in tau accumulation and brain inflammation. The interim results from the study have not yet been disclosed.

High prices and limited coverage pose as speedbumps for obesity drug adoption

While these obesity drugs have exploded in popularity in recent times and are only expected to grow further as their case use increases, they do have certain shortcomings and challenges that are important to address.

These drugs are known to cause several side effects, such as nausea, diarrhea, vomiting, constipation, and ulcers. They can also lead to severe complications, such as pancreatitis, in some extreme cases. While most of the common side effects of the drugs are manageable and justifiable given the risk-benefit ratio, one of the key issues with the drugs is that they need to be taken in perpetuity to keep the weight off. In other words, once a patient stops taking the drugs, the weight comes back. Given that these drugs are priced at more than US$1,000 per month at the moment, taking them constantly becomes a considerable challenge for patients.

Moreover, considered as ‘vanity-use’, these drugs are currently not covered by most medical insurance policies, and thus, patients have to pay for them out-of-pocket. While several employers in the USA are considering including these drugs in their health plans, they are still debating their merit. Employers acknowledge the benefits of these drugs as they help employees who battle with obesity improve their health and, in turn, improve overall performance and employee satisfaction. However, high costs and long-term use act as definite barriers, which make both employers and insurers reluctant to cover these drugs.

Insurers are slowly warming up to the inclusion of GLP-1 drugs in their plans

In March 2024, leading insurance company Cigna stated that it would expand insurance coverage to include weight loss drugs but would limit how much health plans and employers spend on the drug each year. As per Cigna’s benefits management unit, Evernorth Health Services, spending increases for these weight loss and diabetes drugs would be limited to a maximum of 15% annually. The plan offers a financial guarantee and enables employers and health plans to have greater predictability and control over their GLP-1 spending by offering clients (employers) a guarantee that the cost of weight loss and diabetes drugs would not increase by more than 15% annually.

As a part of the effort to limit how much employers spend on GLP-1-based drugs annually, Evernorth has entered into an agreement with Novo Nordisk and Eli Lilly. However, the details of the agreement have not been disclosed.

While this is a good start, the drug would need better coverage by many other insurance players to reach a wider audience.

EOS Perspective

Given that about 12% of the global population and more than 40% of the American population grapple with obesity (as per WHO and 2022 statistics by the National Institute of Diabetes and Digestive and Kidney Diseases, USA, respectively), weight loss drug manufacturers Novo Nordisk and Eli Lilly are sitting on pharma goldmines. The weight loss drugs market, expected to reach US$100 billion by 2030, is poised as one of the most promising sectors for the pharma sector. Thus, it is no surprise that several leading players are investing heavily to join Novo Nordisk and Eli Lilly at the top, either through in-house R&D or through acquisitions.

However, developing these drugs proves to be challenging for drugmakers, as evidenced by the failures of several companies in creating their own versions. We can expect the sector to consolidate further as larger pharma companies look to acquire niche players with their trials being in advanced stages.

Moreover, in a bid to find their footing in this promising sector, pharma players are trying to develop advanced versions of the drug that have benefits beyond just weight loss and offer long-term benefits. This is also because, at the moment, these drugs are not approved by most insurance companies, which makes them extremely expensive for the wider population to afford. This, in turn, is withholding these drugs from becoming mainstream and is thereby preventing them from tapping into their true growth potential. That being said, Wegovy’s recent FDA approval for reducing cardiac complications in people with obesity and heart disease will likely tip the insurers’ coverage scales. Insurance companies are likely to cover the drug in the near future.

Since no other drug in the market offers proven cardiac benefits along with weight loss (including Eli Lilly’s), it is safe to say that Novo Nordisk is way ahead in the race and will dominate the market for the foreseeable future. Thus, to be able to compete in the market, it is not enough for drugmakers to develop obesity drugs offering just weight benefits. They would need to develop drugs that offer higher efficiency or additional therapeutic benefits along with weight loss and price them competitively.

21/02/2024by EOS Intelligence EOS Intelligence No Comments

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

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Pandemics such as COVID-19, Ebola, and the 2009 influenza instilled the need for a well-equipped domestic vaccine manufacturing industry in the minds of African leaders. Currently, due to insufficient local production, the continent depends heavily on imports from other countries, with the imports satisfying about 99% of vaccine demand in the continent. However, thanks to recent significant FDI, the vaccine industry in Africa had a market potential of around US$1.3 billion as of 2021 and is expected to range between US$2.3 billion and US$5.4 billion by 2030, as per McKinsey estimates.

Vaccine sovereignty is the need of the hour for the African continent

One of the most important lessons the COVID-19 pandemic has given to Africa is the pressing need to ramp up vaccine production locally. Biotech firms, such as Moderna and Pfizer, developed COVID-19 vaccines faster than any other producers. However, these vaccines were not easily accessible to most African countries.

Africans, in general, lack access to affordable and quality healthcare. Preventable diseases, such as pneumonia, malaria, and typhoid fever, have high fatality rates across the continent. This calls for localized production of pharmaceuticals and vaccines to lower the economic burden of these diseases and facilitate better access to affordable healthcare.

Currently, Africa relies heavily on other countries, such as China and India, for its pharmaceutical needs. The paucity of localized pharma production aggravates healthcare and vaccine inequity across the continent. To substantiate this, the COVID-19 vaccination rate at the beginning of 2022 in 16 African countries was less than 5% on average.

Currently, Africa consumes around 25% of the global vaccine production, whereas it produces less than 1% of its vaccine needs locally, as per the African Union (AU). Therefore, a lot remains to be done to materialize the goal of achieving 60% of vaccine needs to be satisfied locally by 2040, the vision of the Partnerships for African Vaccine Manufacturing (PAVM) under Africa CDC.

Increasing the vaccine production capacity from 1% to 60% in 15-16 years is not an easy task. Considering this, PAVM designed a continental plan for creating a vaccine production ecosystem capable of achieving the 60% target. This plan, called the PAVM Framework for Action (PAVM FFA), assessed that the African vaccine manufacturing industry would be expected to have increased the number of their vaccine production factories from 13 in 2023 to 23 (11 form, fill, finish, or F&F factories and 12 end-to-end factories) by 2040 providing a total of 22 priority products by 2040. It will require dedicated efforts from all involved stakeholders, such as producers, biopharma companies, industry associations, regulatory bodies, and academia.

Vaccines in Africa Pursuit of Reducing Over-Dependence on Imports by EOS Intelligence

Significant FDI will aid in driving localized vaccine production in Africa

The continent is attracting considerable FDI from the USA and Europe for vaccine development. Several foreign biotechnology firms are partnering with African governments to venture into localized vaccine production.

In March 2023, US-based biotechnology company Moderna partnered with the Kenyan government to set up a production facility for making messenger RNA (mRNA). The proposed annual capacity of Moderna’s first-ever facility in Africa is around 500 million doses of vaccines. The facility is expected to produce drug substances or active pharmaceutical ingredients and the final product for the entire continent.

In another example, a Germany-based biotechnology company, BioNTech, is contemplating commencing production of mRNA-based vaccines in its Rwanda facility in 2025. The construction of the facility began in 2022. With an investment of around US$150 million, this is Africa’s first mRNA manufacturing facility built by a foreign company. The proposed annual capacity of BioNTech’s mRNA facility is about 50 million vaccine doses. BioNTech also plans to set up mRNA factories in other African countries, such as South Africa and Senegal, and plans to produce vaccines for malaria, tuberculosis, HSV-2, and HIV in the future.

In September 2023, the South African government partnered with the KfW Development Bank of Germany. As per the agreement, South Africa will receive €20 million from Germany’s KfW Development Bank over five years for developing and manufacturing mRNA vaccines. The fund will be utilized for equipment procurement and API certification for vaccine production in South Africa.

A consortium of the Global Alliance for Vaccines and Immunizations (GAVI), AU, and Africa CDC established the African Vaccine Manufacturing Accelerator (AVMA) with the intent of fostering a sustainable vaccine industry. The formation of AVMA involved donors, partners, industry stakeholders, and non-governmental and not-for-profit organizations. GAVI planned to expand its supplier base, mainly in Africa, in 2021. Furthermore, the global alliance announced the commencement of around 30 vaccine manufacturing projects across 14 African countries.

Moreover, as of December 2023, over US$1.8 billion is planned for investment by a collaboration between the French government, Africa CDC, and other European and international investors to streamline the development and production of vaccines across the continent.

Desire to ensure vaccine effectiveness is seen as a biased vaccine preference

African governments are not only proactively putting in dedicated efforts to attract considerable FDI to build and strengthen the continent’s vaccine manufacturing industry, but they also focus on good quality, effective vaccine types. However, some perceive this as a lack of interest from the African governments to buy non-mRNA vaccines made by local companies.

For example, Aspen Pharmacare, a South Africa-based biotechnology company, put significant investments in ramping up the capacity of its manufacturing facility to produce viral vector vaccines against COVID-19. The company announced in November 2020 that it would be formulating, filling, and packaging the COVID-19 vector vaccine made by J&J. It also received €1.56 million investment from Belgian investors, BIO, the Belgian Investment Company for Developing Countries, which is a JV between the European Investment Bank (EIB) and several European DFIs.

However, millions of J&J COVID-19 vaccine doses made in South Africa were exported to Europe by J&J without the knowledge of the South African government, to support Europe’s domestic vaccine demand in August 2021, not complying with the initial agreement of vaccine distribution within the African continent. This created a political impasse between European and African governments over the distribution of the vaccines, which, in turn, delayed their production as the standoff resulted in a long waiting time for Aspen Pharmacare to produce the COVID-19 vaccine.

Ultimately, by September 2021, the European countries agreed to return 90% of the J&J vaccines to Africa. In March 2022, J&J gave Aspen Pharmacare the license to manufacture and distribute the vaccine under its brand name, Aspenovax. The expected production capacity of Aspenovax was around 400 million doses. However, not a single order came from African governments.

According to Health Policy Watch News, the reason for this was the rising production of Pfizer and Moderna’s mRNA COVID-19 vaccine distributed by COVAX that was being opted for by most African governments. Thus, in August 2022, Aspen Pharmacare had to close its production line, stating non-existent demand in Africa, partly due to the subsidence of the pandemic and partly due to African governments’ lack of interest in non-mRNA vaccines. The company could not sell a single dose of the vaccine, owing to multiple factors, starting from what was perceived as the lack of government’s intent to purchase home-grown vaccines to delayed production due to the Europe-Africa political clash and the rising inclination of the world towards mRNA vaccines.

It is interesting to note that of the total Covid-19 vaccines Africa administered to its residents, 36% were J&J vector vaccines, shipped directly from the USA.

Technology transfer hub and know-how development initiatives are set

To strengthen vaccine production capacity in low- and middle-income countries (LMICs), the WHO declared the establishment of a technology transfer hub in Cape Town, South Africa, in June 2021. In February 2022, WHO said that Nigeria, Kenya, Senegal, Tunisia, and South Africa will be among the first African countries to get the necessary technical expertise and training from the technology transfer hub to make mRNA vaccines in Africa.

Afrigen Biologics, a South Africa-based biotech firm, is leading this initiative. As Moderna did not enforce patents on its mRNA COVID-19 vaccine, Afrigen Biologics could successfully reproduce the former company’s vaccine, capitalizing on the data available in the public domain. As per an article published in October 2023, Afrigen Biologics reached a stage where its vaccine production capabilities are appropriate for “phase 1/2 clinical trial material production”. Additionally, in collaboration with a Denmark-based biotech firm, Evaxion, Afrigen is developing a new mRNA gonorrhea vaccine.

Besides setting up a technology transfer hub in South Africa, academic institutions are partnering with non-profits as well as companies to reinforce the development of necessary technical know-how and training required for vaccine manufacturing. One such example is the development of vaccines in Africa under the partnership of Dakar, Senegal-based Pasteur Institute (IPD), and Mastercard Foundation. Approved in June 2023, the goal of MADIBA (Manufacturing in Africa for Disease Immunization and Building Autonomy) includes improving biomanufacturing in the continent by training a dedicated staff for MADIBA and other vaccine producers from Africa, partnering with African universities, and fostering science education amongst African students.

Read our related Perspective:
Inflated COVID-19 Tests Prices in Africa

Although significant initiatives are underway, challenges exist

With 13 vaccine manufacturing companies and academic organizations across eight African countries, the continent’s vaccine industry is in its infancy. However, the current vaccine manufacturing landscape includes a mix of facilities with capabilities in F&F (10 facilities), R&D (3 facilities), and drug substance (DS) or active pharmaceutical ingredients (API) development (5 facilities).

One of the challenges African vaccine producers face is not being able to become profitable in the long run. In 2023, a global consulting firm, BCG, in collaboration with BioVac, a South Africa-based biopharmaceutical company, and Wellcome, a UK-based charitable trust that focuses on research in the healthcare sector, conducted a detailed survey exploring stakeholder perspectives on challenges and feasible solutions. The respondent pool consisted of a diverse set of stakeholders spanning across Africa (43%), LMICs (11%), and global (46%). A total of 63 respondents from various backgrounds, such as manufacturers, industry associations, health organizations, regulators, and academic organizations, were interviewed across the regions above. According to this research, most vaccine producers in Africa who were interviewed said that profitability is one of their key concerns. This leads to a lack of foreign investments required for scaling up, which in turn creates insufficient production capacity, thereby increasing the prices of vaccines. Therefore, these producers are unable to meet considerable demand for their products, and their business model becomes unsustainable.

Continued commitment and support from all stakeholders are necessary for achieving a sustainable business model for vaccine producers in Africa and, consequently, for the industry at large. However, it has been observed that the support from global, continental, and national levels of governments and other non-government stakeholders, such as investors, donors, partners, etc., tend to diminish with the declining rampage caused by epidemics in Africa. Therefore, this poses a severe challenge to strengthening the vaccine production industry in Africa.

In another 2023 study, by a collaboration between the African CDC, the Clinton Health Access Initiative (CHAI), a global non-profit health organization, and PATH, formerly known as the Program for Appropriate Technology in Health, involving 19 vaccine manufacturers in Africa, it was suggested that the current vaccine production capacity including current orders to form/fill/ finish using imported antigens is nearly 2 billion doses. In contrast, the current average vaccine demand is 1.3 billion doses annually. In addition, there is a proposed F&F capacity of over 2 billion doses. Thus, if Africa can materialize both current and proposed plans of producing F&F capacity vaccines from imported antigens, the study concludes that the continent will reach a capacity of more than double the forecasted vaccine demand in 2030. Overcapacity will lead to losses due to wastage. Thus, not all vaccine producers will be profitable in the long term. This may challenge the African vaccine manufacturing industry to be profitable.

Moreover, Africa’s current domestic antigen production capacity is lower than what is required to meet PAVM’s vaccine production target of 60% by 2040. In addition, a large part of the existing antigen capacity is being utilized to make non-vaccine products. Although antigen production plans are underway, these will not suffice to narrow the gap between demand and production of antigens domestically in Africa.

EOS Perspective

To create a local, financially sustainable vaccine manufacturing industry with output adequate to support the continent’s needs, it is necessary to create an environment in which producers can achieve profitability.

Initiatives such as technology transfers and funding will only be fruitful when their on-the-ground implementation is successful. This will require the involvement of all stakeholders, from the state governments to bodies that approve the market entry of vaccines. All stakeholders need to be steadfast in their actions to achieve the ambitious target of 60% of vaccine needs to be met from local production by 2040 without compromising on the accuracy and quality of the vaccines.

One of the most vital aspects of the necessary planning is for stakeholders to ensure that even after the pandemic and its aftermath are entirely gone, the effort towards establishing facilities, creating know-how, and training a workforce skilled in vaccine development and production does not stop.

The focus should extend beyond COVID-19, as there are many other preventable diseases in Africa, such as malaria, pneumonia, tuberculosis, and STDs, against which vaccines are not yet produced locally. These areas provide a great opportunity for vaccine producers and associated stakeholders to continue being interested and involved in vaccine production and development in Africa.

07/04/2016by EOS Intelligence EOS Intelligence No Comments

Government Trumps Pfizer Deal

Since its announcement last year, a US$160 billion Pfizer-Allergan merger has been under an ongoing discussion, with great synergies and tax savings expected if the deal was to be finalized, (we wrote about it in our ‘Pfizer-Allergan Deal – What’s in Store for Allergan’ article in February 2016).

However, discussions came to an abrupt end, when the merger was called off on April 6th, 2016 in the wake of changes in tax rules by the US government to check inversions. New rules disregard last three years’ (at the time of deal) acquisitions by a foreign company in the USA in determining its market value. It is a general feeling that the three-year rule was introduced primarily to stop Pfizer-Allergan deal. Since its announcement, the deal was a talking point in political debates with some presidential hopefuls taking an open stance against it.

To secure maximum tax benefits of inversion deal, Pfizer shareholders were required to own 50-60% of the merged entity. Allergan’s market capitalization stood at US$120 billion (against Pfizer’s US$200), owing to three deals, i.e. Allergan-Actavis merger (US$66 billion), Forest Laboratories acquisition (US$25 billion) and Warner Chilcott purchase (US$5 billion), struck in last three years, thereby giving Pfizer shareholders more than 50% of the combined entity. However, this will not be the case now due to drastic reduction in Allergan’s market value as a result of three-year window provision. This also means that both the companies will have to go back to the drawing board.

For Pfizer, this means the need for an increased focus on management of its vast portfolio of drugs (a mix of patent and off-patent products) with an intent to further improve profitability. While Pfizer’s patented drugs command higher prices, the off-patent ones are subject to price decline thereby impacting the company’s profitability. After the announcement of Pfizer-Allergan deal, there were speculations about sale/spin-off of Pfizer’s off-patented portfolio. However, with revenue loss due to the broken deal, the plan (if still any) to sell off-patented business is likely to be put in freezer for some time to come. This could also mean more efforts on research and development front, and being inherently a research driven company, Pfizer has some potentially lucrative drugs in pipeline (including cholesterol lowering and cancer drugs).

For Allergan, the broken deal means looking for alternative ways to strengthen its position outside the USA. The company can take inorganic route to achieve this. No headway was made towards operations restructuring of the merged entity. Therefore, in all likelihood, the research and development assets of Allergan will remain intact, one positive outcome for the company out of the broken deal, as it has some good candidates in the field of ophthalmology, urology, and women’s health. With sale of its generic business to Israeli rival Teva Pharmaceuticals in July 2015, Allergan showed the intent to focus on patented products, therefore the company will have to look for means to raise its R&D budget.

The broken Pfizer-Allergan deal will remain in discussion in coming days from the point of view of missed opportunities for both Pfizer and Allergan, as well as for the political angle involved. Even if the decision was politically motivated, it may have put moratorium on inversion as a strategy for the time being, and it would be interesting to track moves not only in the pharmaceutical space but in other industries as well, following the new regulatory regime.

03/02/2016by EOS Intelligence EOS Intelligence No Comments

Pfizer-Allergan Deal – What’s in Store for Allergan

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In November 2015, Pfizer and Allergan announced a US$160 billion merger deal. Once finalized, the Pfizer-Allergan deal would follow three large mergers/acquisitions concluded by Pfizer in the last 15 years. Though relocation to Ireland to save higher corporate tax in USA is apparently the main purpose of this merger, it is expected to create a pharmaceutical powerhouse with more than US$60 billion in annual revenue. In the light of competitive advantage this deal is anticipated to yield, it becomes imperative to look at Pfizer’s evolution since its first mega deal in 2000.

Pfizer acquired US-based Warner-Lambert in a US$110 billion deal in 2000. With this acquisition, Pfizer gained ownership of blockbuster anti-cholesterol drug Lipitor, besides some popular consumer health brands, such as Listerine. Lambert deal was shortly followed by US$60 billion purchase of US-based Pharmacia in 2003. The deal, while catapulting Pfizer’s revenue by more than US$12 billion, allowed it to gain control of successful brands, such as Celebrex (inflammation) and Xalatan (glaucoma), along with R&D pipeline of cancer drugs and a specialist-focused sales force of Pharmacia.

Pfizer waited six years for its next acquisition, and bought US-based Wyeth for US$68 billion in 2009. This deal came amid imminent expiry of Pfizer’s 14 patents through 2014, including its best-selling drug Lipitor in 2011. Pfizer looked to benefit from Wyeth’s leadership position in vaccines, nutritionals, and biologics, including Prevnar, the first pneumococcal vaccine for infants. Wyeth’s portfolio potential had indeed been locked, as evident in the net 30%-90% increase in sales of its key brands between 2009 and 2014, post-acquisition.

These three deals helped Pfizer in becoming a US$50 billion company with a diverse product portfolio. However, it came with a challenge of ensuring operational efficiency and leveraging synergies with acquired companies. This was achieved through a range of adjustments, including lay-offs to eliminate overlaps and to consolidate various functions. Pfizer deals were severe on the employees of acquired companies, with more than 90,000 jobs eliminated (which may have included those lost to attrition) between 2000 and 2014. At the time of each deal, there were apprehensions regarding the future of research and development in Pfizer. Though the company managed to maintain its R&D budget at about 16% of revenues, several sites (including six from Wyeth and two from Pharmacia) were closed post acquisitions. It was soon reflected in the company’s product pipe line, with only 17 applications filed for new product approval between 2007 and 2014, in contrast to 43 during 2000-2006.

To sum up Pfizer’s strategy, the company acquired rivals with blockbuster brands to boost its topline, and to benefit from pooling of resources. The strategy worked on most counts, except for Celebrex where the sales failed to take off partially due to pull-out (from market) of a rival drug (Merck’s Vioxx) in 2004 owing to safety reasons. Notwithstanding the criticism for massive lay-offs, Pfizer managed to create a lean organization, thereby improving its revenue per employee.

Pfizer’s next acquisition target, Allergan, came in to existence following Ireland-based Actavis’ acquisition of USA-based Allergan Inc. in March 2015, post which the combined entity was renamed Allergan. Allergan then sold its generic drugs business to Israeli rival Teva Pharmaceuticals in July 2015.

As Pfizer’s deal with Allergan looks in sight, there are speculations regarding future shape of the combined entity in terms of employee strength, sales focus, and future product pipeline (i.e. R&D).

Pfizer-Allergan deal involves trimming of sales and administration expenses by more than US$1.0 billion. This is likely to be achieved (mostly) in North America where Allergan operations are concentrated.

Cuts worth more than US$600 million are expected in R&D. With Teva deal, Allergan showed intent to focus on branded proprietary drugs, and Pfizer is also a predominantly green-field research organization. Therefore it is not clear yet, which product programs will face the ax due to little overlap in research focus of two companies.

As Allergan declared end to lay-offs in June 2015, it was expected that most of the Actavis acquisition-related restructuring activity was over by the time Pfizer-Allergan deal was announced. This means the cost savings linked with Pfizer-Allergan merger will result from the existing operations (as of November 2015) of the two companies.

EOS Perspective

Based on precedence of Pfizer takeovers, there is a likelihood that Allergan might bear most of the brunt of cost cutting measures. However, at the outset, a simple merger is not likely to impact either efficiency or earnings (from R&D perspective) of the combined entity due to nearly identical revenue per employee (as of 2014) for both the companies, and Allergan’s significantly lower R&D expenditure (8% of its revenue vs. Pfizer’s 16%).

Cost cutting is likely to be undertaken with an eye on revenue and profitability in mid to long term. From Allergan’s perspective, we anticipate this to be achieved through the following:

Focus on products in the pipeline with good growth prospects: Allergan’s Rapastinel (anti-depressant) and Vraylar (schizophrenia) are in this category; another option for Pfizer-Allergan is to focus on drugs that are in advanced stages of trials i.e. Phase III and IV
Focus on high revenue earning products: While most Pfizer products (including those off-patented in recent years) generate revenues in the range of US$200 million to US$5 billion, Allergan’s portfolio is still underdeveloped (due to limited global exposure) except for few products from central nervous system (CNS), gastroenterology, and women’s health segments

At present, only mere speculations can be offered regarding the future shape of the combined entity, as no concrete steps have been announced. It will be interesting to track the decisions taken by Pfizer-Allergan in the coming months to achieve targeted cost savings.

23/05/2013by EOS Intelligence EOS Intelligence No Comments

Will Pharma Tweet Louder? 6 Rules of Doing it Right on Social Media

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Initially considered to be exclusively a tool for common people to connect with friends and share their private pictures, social media platforms have now gained the status of a potent communication channel eagerly used by companies across the world. While the expansion of social media is influencing the way businesses are conducted today, pharma and healthcare industry has been somewhat slow and reluctant to use it to its fullest potential.

By 2012, Facebook user base crossed 1 billion mark, increasing by 200 times since 2005, while Twitter recorded tremendous growth, reporting 200 million active users sharing 400 million tweets per day. While some industries such as consumer goods, retail, and hospitality have been benefitting from engaging with their customers through a range of social media platforms, other sectors, including pharma and healthcare, have been slow to join the ‘social crowd’.

Points of concern

There is a reason why healthcare-related sectors were late on the social media map. Creating an open platform for communication on health and drugs aspects, raises a range of concerns: the FDA regulations, patient confidentiality, cyber security, unavoidable off-label use discussions, uncontrolled negative comments, and risks of providing wrong medical advice that could lead to lawsuits. The FDA in particular, plays an important role here, through its Division of Drug Marketing, Advertising and Communications (DDMAC), which lays out the rules of the content that can and cannot be communicated, what content must be included and the manner in which the communication must occur. The fears associated with social media activity monitoring by the FDA, typically originate from three problems:

Lack of clarity and formal guidelines – in 2011, the FDA published draft guidelines, and it is yet to develop definitive rules on social media policy. The FDA is acting slow, and there is no clarity on dos and don’ts for social media engagement, yet the authority regularly scans the social space to monitor risky communication, while pharma companies find the rules of the game ambiguous
User-initiated off-label use discussions – a common issue in pharma social media platforms is user questions and discussions on off-label use of drugs, i.e. using a drug in a different way than described in the approved drug label or leaflet. This is considered unsolicited content and companies must respond and correct such a content occurring in public forum as these discussions might encourage dangerous experiments with drugs by patients or might be confused with recommended and approved use of a drug
Adverse event reporting obligation – the FDA obliged pharma companies to immediately report any adverse drug effect or reaction they learn about. Social media give platform for large numbers of patients to share their experience with adverse drugs effects, and the companies are afraid they will have to report it, which may cause investigations, bad press, and might lead drug being banned from sale

Similar fears are faced by non-US pharma companies too, as the FDA’s local counterpart authorities introduce similar regulations on communication via social media, which at times can be even stricter than the American ones.

Game worth the candle

Ignoring the risks by pharma companies can unfold a range of undesirable scenarios, a fact that has kept many drug makers hesitant of engaging in social media for quite some time. But this does not mean that pharma and healthcare organizations are still not present in social media at all. To the contrary, pharma companies, healthcare providers, device manufacturers, and health insurers have started to listen and engage with users through social platforms, though many of them still do it cautiously and have still not been able to unlock the social media’s full potential. These players have started to understand that with careful moves, the benefits will outweigh the risks:

generate engagement and discussion around health issues, which contributes to the positive reputation and brand image, and obviously – increase sales,
get quick, cheap, first-hand information on drugs’ effects on a large scale, which brings valuable insights that are not available from regular clinical trials whose scale is always smaller,
gather information invaluable in building marketing strategies, including pointers on price perceptions, drug availability as well as patients’ opinions about competitors’ drugs.

Who’s doing it?

Though it was estimated that in 2011, 90% of the pharmaceutical industry was still inactive on social media, currently, this has changed (though today’s participation share is unknown). Several pharma-sponsored communities are now active across Facebook, Twitter, YouTube, Google Plus, on one or multiple platforms, with a differing level of interactivity and different weight being put on inbound versus outbound marketing. Some of the examples include:

Roche’s Accu-Check Diabetes Link, a diabetes-support community with information, discussions, and blogs
GSK’s Alli Circles well-being, weight loss, and health community
Novartis’ CV Voice for cystic fibrosis patients and Chronic Myelogenous Leukemia own community-based site CML Earth
Pfizer’s community ‘getold.com’ targeting the expanding elderly group of the American population
Sanofi US’ Diabetes support community
Soon-to-be-launched Boehringer Ingelheim’s Facebook-based game, where players create and operate their own pharmaceutical firm, and discover imaginary medicines through virtual laboratory

Getting it right

It appears that the healthcare industry is finally attempting to catch up on the social media revolution in spite of a slow start. From primarily information dissemination, it is now moving towards real time engagement between physicians, patients, and other stakeholders. Soon, developing a social media policy will no longer be an option for pharma companies. But this should not be seen as a burden, but rather as an immense opportunity for the pharmaceutical companies to develop trust, build brand image, and impart health education. Drug makers that want to be successful on their social media path should consider 6 basic rules of online presence for pharma companies:

Take your risks seriously – social media engagements, especially in pharma domain, always raise privacy, legal, and confidentiality concerns among the participants and monitoring bodies. Extra cautiousness in operating online communities is of utmost importance, including constant monitoring of the content being added by individual users and patients. Social platforms also pose risk of incorrect drug information or unfair accusations that might damage your image, but it can be flipped to an advantage, using the platform to quickly clarify and avert unwanted comments, provided that you have a dedicated, competent staff handling your social media
Control your speakers – given the high risks and ambiguity of formal guidelines, there is a need for internal policy or guideline book listing dos and don’ts for online communication, content approval process, crisis management practice, confidential information sharing policy for employees running social platforms on behalf of the company
Know your target audience – the social media pharma-related content must stay relevant and target focused groups to have the right impact. Patients with a particular disease or ailment look for relevant, detailed information, and they typically already know quite a bit about the problem. Expertise must be shown along with dedication to creating high quality content, that is useful, new, and (ideally) entertaining
Get the objective right – social media is not another advertising board. The primary aim of the social media presence is to generate engagement as well as share and manage knowledge by facilitating interaction and discussions. This must take precedence over advertising
Be transparent – transparency is always appreciated by consumers and patients. The link with the company must be clear, users working for the company must disclose their affiliation, and negative comments, unless unjustified or vulgar, cannot be censored
Understand that social media are not a lone island – social media activity and content must be aligned with overall marketing strategy and be used cohesively with all other marketing channels, ideally to complement each other. Social media cannot become a neglected child of the marketing department in a long run, it must be maintained actively and linked to other marketing efforts whenever possible (e.g. to disseminate important announcement teasers, generating traffic to blog entries, or provide interactive content as part of larger marketing campaign including traditional media)

Social media engagements by drug makers might seem only as a nice publicity stunt, but it is so much more than that. Pharma companies, as most players across many industries, finally started to realize that listening and engaging with conversation with the customer pays off in many aspects. Just as was the case in consumer goods or retail sectors, social media will continue to change the pharma industry on a large scale. Players who want to matter, should not allow themselves to stay behind, even considering the risks involved.

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