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REGULATORY LANDSCAPE

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Estonia's Rise as Europe's Fintech Powerhouse by EOS Intelligence
by EOS Intelligence EOS Intelligence No Comments

Estonia’s Rise as Europe’s Fintech Powerhouse

Estonia, a small Baltic country with a population of 1.4 million, is in the news for all the right reasons: its burgeoning fintech sector. With a market size of €15.2 billion in 2023 and projected growth of 5.7% CAGR from 2023 to 2028, Estonia’s number of fintech companies has increased by 23% from 2020 to 2023. The country has 264 fintech startups, half emerging between 2020 and 2022. Strategic investments in digital infrastructure, a progressive regulatory environment, and a tech-friendly culture make Estonia a leading hub for fintech innovation in Europe.

Estonia has become an important name in the fintech sector ever since its financial institutions started using fintech in the early 2000s. It has become the leading fintech hub in Europe, with 2.3 fintech unicorns (startups with a valuation exceeding US$1 billion) per million population.

Most fintech startups, accounting for 87% of all fintech companies in Estonia, fall into six categories: digital asset exchange (33%), digital lending (15%), enterprise technology provisioning (14%), digital payments (11%), wealthtech (9%), and digital capital raising (6%).

Startups dominate Estonia’s fintech landscape with fewer established companies, indicating a favorable environment for new players. Digital asset exchange services that facilitate the trade of cryptocurrencies or digital currencies for other assets form the lion’s share of these startups. This includes Tallinn-based companies such as AsicVault and Guardtime.

Finding customers is a concern for Estonia’s fintech sector

Fintech is flourishing in Estonia despite various challenges that players must navigate. Typically, these challenges affect the smallest and newest entrants to the market the most.

One of the significant challenges that businesses can expect is finding loyal customers for their solutions, according to the 2023 report by the TalTech School of Business. In their research, the respondents indicated finding customers as the most critical problem in two survey editions, 2021 and 2023.

Since Estonia has a small population of 1.4 million, the domestic market is relatively small. Businesses across sectors, including fintech, often face limitations in expanding their customer base. This can force companies to look beyond national borders to achieve significant growth, which can be difficult for new players.

Estonia's Rise as Europe's Fintech Powerhouse by EOS Intelligence

Estonia’s Rise as Europe’s Fintech Powerhouse by EOS Intelligence

Rising costs are affecting smaller and newer players

The financial side poses a substantial challenge for players with limited budget planning to start and expand a fintech firm in Estonia. Estonia used to be a place of low living costs and cheap labor since its independence in 1991. However, the rising operation costs now affect the fintech landscape. A 2023 report published by the European Commission indicated that in the fourth quarter of 2022, compared to the same period in the previous year, Estonia saw a 10.1% increase in hourly wage costs. This can harm small new players looking to enter Estonia’s fintech landscape.

Competition with Big Tech in foreign markets can challenge expansion

Estonian fintech companies attempting to expand into more mature markets can face several hurdles. For example, a high degree of sophistication and regulation characterizes the UK financial services sector, a desired expansion target, leaving little room for new entrants without an established brand presence or a solid track record.

Establishing trust is paramount for fintech startups, as consumers and businesses often prefer providers with known reputation, selecting them through word of mouth or established market presence. As a result, new entrants must devise comprehensive (and often cost-intensive) marketing strategies to overcome these initial credibility barriers.

Increased competition from established financial institutions that leverage their substantial resources to compete with startups can exacerbate these challenges. Big Tech firms such as Google, Amazon, and Apple have also begun to venture into the financial services sector. These companies possess strong brand recognition, customer trust, and rich data sets, enabling them to overshadow smaller fintech operations.

Cross-border expansion signals Estonia’s thriving fintech sector

Estonia’s cross-border expansion activities highlight its flourishing fintech sector. Fintech ranks as the second largest industry within the Estonian startup ecosystem, following business software and human resources, accounting for 13% of the nation’s startups. In terms of revenue, it also holds the second position, generating €196 million in turnover as of 2023.

Estonian fintech startups are actively pursuing opportunities beyond national borders. For instance, the financial cybersecurity firm Salv, based in Estonia, has extended its operations to Latvia and is planning further expansion to Lithuania and the UK. The firm aims to promote its AML solution, Salv Bridge, in these markets.

Additionally, in June 2024, Depowise, a startup located in Tallinn, announced its plans to expand into Ireland and the UK to enhance its market presence in the region.

Estonian fintech startups are increasingly seeking opportunities outside their home market, demonstrating the sector’s robust success and appetite for expansion.

Several catalysts are fueling the growth of Estonian fintech

Ease of doing business

The country ranks 18th in the World Bank’s ease of doing business index, beating more developed countries such as Germany (22nd), Canada (23rd), and Ireland (24th) as of 2019. This favorable business environment in the country is one of the main factors making it an attractive location for fintech businesses. According to the World Bank, the country has a highly conducive tax system, ranked 12th in the ease of paying taxes.

Efficient corporate tax systems

Due to its efficient tax policy and straightforward tax compliance frameworks, Estonia holds the top spot in the 2023 International Tax Competitiveness Index published by Tax Foundation, a US-based think tank. This allows companies to spend considerably less time (five hours per year in Estonia compared to 42 hours per year in an average OECD country) on tax-related tasks.

The Estonian tax system also boasts a similarly low compliance burden (resources and costs associated with complying with regulatory requirements) for other taxes, including value-added tax (VAT).

The country’s corporate tax rate is 20%, but it only applies to distributed profits. This means that if a company reinvests its profits back into the business, it does not pay any corporate income tax until it distributes those profits as dividends. This has significantly encouraged reinvestment, growth, and expansion of businesses, including fintech companies.

Internet freedom

Internet freedom is robust in Estonia, and the country is known for its numerous e-government initiatives. For the past several years, Estonia has maintained the second position globally in the Freedom on the Net reports by the US-based NGO Freedom House, indicating a very high internet freedom rating in the country. This minimal restriction on online content facilitates easy information and idea transfer and helps businesses, including fintech companies, to flourish.

Cybersecurity

Though online activities have minimal restrictions, the Estonian authorities have implemented proactive measures to ensure cybersecurity. The 2020 Global Cybersecurity Index (GCI) published by the International Telecommunication Union (ITU) ranks Estonia as the third most cybersecure nation. This is especially beneficial for fintech companies since most of their operation is online.

Estonia is a cashless society with around 99% of transactions occurring digitally. This creates a significant demand for innovative fintech solutions. Startups and established companies take this as an opportunity and offer services such as digital wallets, payment gateways, and peer-to-peer lending, among others, to which strong cybersecurity is essential.

E-residency scheme

Estonia’s e-residency program supports fintech investments by allowing foreign entrepreneurs to establish businesses remotely without a physical office. This program provides online business owners, digital entrepreneurs, and freelancers with a digital Estonian ID, granting access to various local services such as business registration, banking, payment processing, and tax management.

Since its introduction in 2014, the e-residency program has grown significantly, with 117,000 individuals from 185 nationalities obtaining e-resident status and creating over 31,800 Estonian companies. This represents roughly one in five new companies annually and links 38% of startups to e-residents. The initiative has also contributed €244 million to Estonia’s economy, generating €67.4 million in direct revenue in 2023 alone, with associated costs of €7 million, achieving a nearly tenfold return on investment.

Regulatory sandboxes

A regulatory sandbox (RS) is a framework established by regulators that allows businesses to test new products, services, or technologies in a controlled environment for a specified time. This concept is prevalent in various sectors, including finance, transportation, and healthcare.

In March 2024, Estonia expanded its RS through the Accelerate Estonia program to support non-fintech startups, inviting a medical startup, Your Cue, and a clean energy startup, O-Innovations. While regulatory sandboxes are more common in the US fintech sector, European countries such as the UK, Poland, and Spain are also developing their own. As of October 2023, there were 14 fintech sandboxes in 12 EEA countries, including Estonia, which launched its sandbox in August 2023 but has yet to invite any fintech participants.

Technological advancements dictate the direction of development

The use of newer and more innovative technologies is on the rise. Many Estonian fintech startups now use technologies such as artificial intelligence (AI), machine learning (ML), the Internet of Things (IoT), etc.

An example is Depowise, which has developed innovative AI-powered solutions to automate critical functions for financial institutions, including compliance oversight, cash flow monitoring, and digital asset safekeeping.

Companies such as Value.Space, an insurtech firm founded in Estonia and currently headquartered in London with an operating office based in Tallinn, uses deep tech (advanced technologies engaged to address and revolutionize the fields they are used in) such as InSAR (Interferometric Synthetic Aperture Radar), AI, predictive analytics, and satellite imagery to help businesses monitor and assess the risk of damage to commercial assets.

Open banking and embedded finance are the budding trends in Estonia’s fintech solutions developments. BaaS (Banking as a Service) enables secure data sharing and collaboration between financial institutions, technology companies, and customers. Open banking facilitates the entry of new players into the Estonian market through strategic partnerships with local fintech companies. This dynamic allows fintech and technology companies to challenge traditional financial models, creating innovative customer engagement methods with financial institutions. Furthermore, open banking grants developers access to an extensive financial data repository. This accessibility has spurred the emergence of novel fintech business offerings, including budgeting applications, robo-advisors, and automated savings solutions.

Embedded finance involves fluidly incorporating financial services and products into non-financial platforms, such as e-commerce websites, mobile apps, or other digital landscapes. One of the leading examples of fintech companies in Estonia leveraging embedded finance is Inbank, which has developed a portal for solar panel installers to provide financing solutions to their customers.

Opportunities for financial cybersecurity players emerge with increasing crime

Online financial crime and money laundering protection are also gaining traction in the development of fintech solutions. This has particularly accelerated following the 2007 mass cyberattack on a range of institutions and the 2017 money laundering scandal involving Danske Bank’s Estonian branch. Since those events, Estonia has seen a surge in demand for services and products providing solutions in compliance and AML measures.

An example of a solution meeting this demand is SalvBridge, Salv’s anti-money laundering solution, which uses advanced analytics and ML to detect and prevent financial crimes in real time. It also helps financial institutions meet increasingly stringent regulatory requirements and combat money laundering effectively.

Similarly, Tallinn-based Veriff offers solutions to help reduce fraud and ensure regulation compliance. Veriff protects against identity fraud and theft by automatically verifying customer identities through an AI system that assesses various technological and behavioral factors, including facial recognition.

Serokell is another Tallinn-based R&D company offering cybersecurity solutions for fintech companies. Its solutions use functional programming, making it ideal for the complex fintech sector.

Demand for such solutions will likely continue to grow, offering lucrative opportunities for players operating and innovating in this space.

Estonia’s fintech scene is shifting towards sustainable investing

As with many other industries, sustainability and environmental awareness have entered the fintech playing field. Some players attempt to improve their sustainability score while expanding their investment portfolios to include sustainable exchange-traded funds.

Companies that operate using carbon credits and sustainability fintech players are some of the newer market entrants. An example is Grünfin, founded in 2020, which facilitates investments in sustainable stocks.

Several fintech companies are also increasingly leveraging carbon credits to enhance their sustainability practices and offer financial solutions to clients. A notable example is the partnership between XTCC, an Estonia-based company specializing in exchange-traded carbon credits, and Finmaal, a UAE-based fintech platform. This collaboration allows customers purchasing financial products, such as insurance and banking, to offset their carbon emissions at the point of sale, thus integrating sustainability measures with financial transactions.

These activities reflect a broader trend in which fintech firms are leveraging cloud technologies and financial instruments to maintain a lower carbon footprint while contributing to carbon neutrality goals. It is fair to expect that the trend of focus on the environment and sustainability will gain more traction in the future.

EOS Perspective

Estonia is emerging as a strong and resilient ground for fintech startups as well as established fintech businesses. Given the country’s favorable conditions, this growth will likely continue. Industry experts expect the market to advance further in key areas such as digital payments, blockchain technology, and AI-driven financial services.

While no single company has a dominant market share, notable players such as Wise, Guardtime, and Bolt are likely to continue strengthening their positions. These companies have the financial resources, established brand presence, and technological capabilities to drive innovation and expand their market reach. Players can also expect increased competition from established financial institutions, such as banks, which are likely to enter the space.

New players and startups can expect a better level playing field in niche fintech areas, such as financial security or climate fintech, and other related areas often working in tandem with fintech, e.g., insurtech or regtech.

With several countries, including China, Egypt, Qatar, Oman, Morocco, Algeria, and Tunisia, banning bitcoin or other cryptocurrency mining due to high energy use and safety issues, climate fintech startups can use this opportunity to expand their operations to offer more sustainable financial solutions.

Fintech startups offering cyber protection and customer data safety are expected to grow significantly in the coming years, especially with large financial institutions such as US-based Evolve Bank & Trust experiencing cyberattacks and a subsequent data breach in 2024.

The new tax policies scheduled to take effect in 2025 will increase individual and corporate tax rates from 20% to 22%. These changes are likely to create some ripples in the fintech sector, at least in the portion of players’ profits that are not reinvested. The new tax laws may increase the operating costs for fintech companies, which could somewhat stifle innovation. This new development may curb investment, especially for small, budding players.

Over time, consolidation is likely to occur as the Estonian fintech market will head towards maturing. Larger companies may acquire smaller startups to expand their product offerings and increase their market share.

While development is rife in the global fintech sector, with its tech-savvy culture, strategic digital infrastructure investments, and progressive regulatory conditions, Estonia will likely carve out an even more prominent place in the fintech landscape.

Open Banking Sparking a Wave of Innovation in Financial Services by EOS Intelligence
by EOS Intelligence EOS Intelligence No Comments

Open Banking Sparking a Wave of Innovation in Financial Services

The adoption of open banking is leading to innovation across financial solutions such as account-to-account payments (A2A), personal finance management (PFM) apps, embedded finance, and banking-as-a-service (BaaS) by enabling real-time data-driven insights and personalized financial services. It is paving the way for a more dynamic financial landscape. Open banking has evolved rapidly since the revised Payment Services Directive (PSD2) came into force in Europe. While challenges exist, adopting open banking solutions, aided by introducing regulatory and security measures, holds the potential to revolutionize the financial services sector.

The introduction of APIs transformed banking services

Open banking has emerged as a transformative force, changing how financial data is shared, and services are offered to consumers. It securely provides third-party financial service providers access to consumer’s financial information with their consent through an application programming interface (API). It aims to foster innovation in financial services, encourage healthy competition, and give consumers more control over their banking information. Several banks across countries, including Citi, Barclays, and Deutsche Bank, have started providing access to their APIs.

Regulatory initiatives and consumer demand lead to open banking growth

While open banking has existed for a long time, it gained traction when the PSD2, a European regulation focused on creating a more open, competitive, and secure payment landscape across Europe, came into effect in 2018.

Since then, several countries have introduced open banking regulations to support its adoption. For instance, in the UK, the open banking initiative, led by the Competition and Markets Authority (CMA, the UK’s principal authority responsible for strengthening business competition and preventing anti-competitive activities), became effective in 2018. In addition to the European countries, Australia, New Zealand, Brazil, and South Africa, among others, have introduced regulatory measures to drive the adoption of open banking.

Countries across the globe are adopting various approaches to open banking, including regulatory-led, market-led, and hybrid approaches. While Europe has taken a regulatory-led approach, adopting open banking in the USA, Canada, and China is driven by consumer demand and technological innovations. Consumers prefer to have control and transparency over their financial data. While there are currently no regulatory frameworks for open banking in the USA, the Consumer Financial Protection Bureau (CFPB) has proposed rules to protect consumer data rights, which will aid in facilitating the adoption of open banking.

Several countries, such as India, South Korea, Japan, Hong Kong, Russia, and Singapore, have adopted a hybrid model, including both regulatory and market-led initiatives. These countries do not have mandatory open banking regimes, but policymakers are looking to introduce initiatives to accelerate open banking adoption. For instance, in Singapore, the Monetary Authority of Singapore (MAS) and the Association of Banks have published an API playbook. This publication aims to support data exchange between banks and fintech players.

The growing emphasis on introducing regulatory measures to ensure data security will likely drive the adoption of open banking.

Open Banking Sparking a Wave of Innovation in Financial Services by EOS Intelligence

Open Banking Sparking a Wave of Innovation in Financial Services by EOS Intelligence

Open banking is driving innovation in financial solutions

The adoption of open banking is transforming financial solutions, including A2A payments, variable recurring payments (VRP), PFM apps, BaaS, and embedded finance, by enabling faster, more convenient, secure, and personalized financial services.

A2A payments and VRP

Open banking allows secure access to real-time bank data to third-party providers, enabling process automation, speeding up A2A payment transfers, and providing a better user experience. Increasing adoption of open banking globally is expected to make international A2A payments more viable and secure.

Digital wallet platforms such as Apple Pay, Google Pay, and Stripe are looking to integrate open banking on their platforms to provide enhanced user experience. In September 2023, Apple soft-launched a new iPhone wallet app in the UK integrated with an open banking framework to replace traditional banking apps as the preferred platform for accessing information related to their account balance, spending history, etc.

Open banking also encourages the widespread adoption of variable recurring payments by giving consumers more transaction control and transparency. The use of variable recurring payments is expected to increase across various commercial payment services, such as utility bills, subscriptions, and insurance premiums, in the coming years.

PFM apps

Access to financial data enables PFM apps to share more effective and personalized financial advice with consumers. A real-time snapshot of the overall financial health of the consumers helps them make long-term financial decisions.

BaaS

Banking-as-a-service platforms are likely to develop due to the adoption of open banking, allowing non-banking entities to provide financial services without becoming certified banks. This offers consumers a variety of payment and credit options, as well as more personalized finance solutions, expanding the industry offering.

Integrating BaaS in retail is being explored to improve customer loyalty programs and provide seamless payments. Also, the scope of services is likely to expand rapidly, from offering banking services to individual consumers to small and medium-sized enterprises (SMEs) and large corporations in the near future.

Embedded finance

Open banking has become the driving force behind the rise of embedded finance, enabling businesses and corporate clients to enhance operational efficiency and user experience. While retail and e-commerce platforms are some of the first to adopt embedded finance, the adoption is likely to increase in less digitalized spaces such as real estate as well.

Synergy with AI and blockchain offers scope for advanced innovation and security

Open banking provides a data-rich environment by aggregating data from various financial institutions for AI algorithms to analyze and utilize for decision-making. It is expected to benefit AI algorithms further by incorporating new features such as data categorization and anomaly detection in the coming years.

On the other hand, AI is likely to increase the effectiveness of open banking by analyzing individual consumer data and enabling the offering of personalized services. AI and open banking will likely help financial institutions develop innovative products.

While both AI and open banking complement their financial services, they can lead to data misuse or unauthorized access concerns, highlighting the need for strong regulatory measures to keep up with the evolution of open banking and AI.

Blockchain technology will likely become more common in open banking as it will enhance the security and transparency of financial transactions. It will likely reduce the risk of data breaches and unauthorized access to consumers’ finances. Additionally, it will likely make it easier for consumers to share their data by simplifying the authentication and consent processes.

Open banking services have expanded from basic payment initiation to open finance

The open banking framework has evolved from basic account information and payment initiation services to open finance, including access to data from various accounts, including savings, investments, pensions, insurance, and mortgages.

Countries such as India, South Korea, Australia, and Brazil have moved from open banking to open finance to develop a more connected financial ecosystem. In February 2024, South Korea also introduced two initiatives focused on including business data and providing offline open banking services.

In Europe, the European Commission is also pushing towards open finance by introducing the Financial Data Access (FiDA) regulation, a framework to enable secured sharing and access of financial data.

Open banking will diversify consumer options, with non-financial companies such as telecom providers, e-commerce platforms, and utility companies offering innovative financial products. They will likely enter into partnerships with banks to provide integrated services to consumers, enhancing their offerings and creating an interconnected financial ecosystem.

Lack of standardized APIs affects the open banking adoption

While open banking is gaining traction, specific challenges, such as lack of standardized APIs, integration with legacy systems, privacy compliance, and data security, are affecting its adoption.

The lack of standardization of APIs across financial institutions is the key challenge in adopting open banking. Third-party providers are usually unable to adapt to different APIs and provide seamless data sharing between systems.

Various financial institutions also face difficulty integrating open banking into their legacy systems, making the integration process complex and expensive. Banks must first update their systems by investing in technology upgrades and partnering with fintech solutions providers to overcome integration challenges.

As the adoption of open banking increases, the chances of data breaches might also increase, highlighting the need to protect customer data and compliance with privacy regulations. Banks are looking to adopt measures such as encryption, clear usage policies, and regular audits to protect customer data. The European Union has also put regulations such as the General Data Protection Regulation (GDPR) and the Digital Operational Resilience Act (DORA) in place to protect customer data and improve the digital security of financial institutions. Advanced security measures solutions, including tokenization and dedicated API gateways, can also help safeguard customer data.

Lack of awareness among consumers is another key challenge. Users are often unaware of open banking and are reluctant to share their financial data due to privacy concerns. Initiatives aimed at educating the users about security and regulatory norms related to open banking by banks can help overcome this challenge and drive adoption.

EOS Perspective

The shift to an open banking model can transform the future of digital banking. The key driving factors for the users are the ease and clarity of the interface, which are likely to replace the traditional banking infrastructure and ownership of consumer data.

The expected introduction of PSR1 in 2026 will likely improve competition and consumer protection in the payments market, which will likely drive the adoption of open banking. PSR1 will help enhance fraud prevention, improve consumer rights and protection, standardize payment regulations, and enhance open banking functions.

The introduction of regulatory and security measures and growing awareness about open banking and its benefits are also likely to aid this growth. A phased implementation of open banking will help with greater adoption of open banking by gradually introducing the concept to the consumers and helping them adapt.

Open banking will benefit banks by providing better customer insights, encouraging innovation, and creating an additional revenue stream through API monetization. However, increasing competition from fintech and non-financial institutions entering the market will likely pressure banks to transition to open banking. The shift to open finance will further increase the competition in the industry. We will likely witness banks entering partnerships with fintech players to develop and offer innovative financial services for their consumers.

The financial sector is embracing open banking as a means to offer creative and innovative financial solutions to enrich the user experience. Open banking will likely evolve into a broad ecosystem of connected services, streamlining the consumers’ products, services, and applications into one, providing a seamless experience.

New Directions in Alzheimer’s Diagnostics Will Blood Tests Replace CSF and PET by EOS Intelligence
by EOS Intelligence EOS Intelligence No Comments

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

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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.

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

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.

What’s Fueling Asia’s Drive to Develop Wholesale CBDCs by EOS Intelligence
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What’s Fueling Asia’s Drive to Develop Wholesale CBDCs?

The emergence of Central Bank Digital Currencies (CBDCs) has become a central focus in the global financial space, as it offers the potential for revolutionary shifts in how the world conducts and manages monetary transactions. While much of the spotlight has been on retail CBDCs, wholesale CBDCs are gaining momentum globally. Asia is leading the pack in developing wholesale CBDCs that offer opportunities that may significantly impact the global financial landscape.

Asia is outpacing developed countries in the drive toward wholesale CBDCs

Wholesale CBDCs are digital forms of a country’s fiat currency. Unlike retail CBDCs, only a limited number of entities can access wholesale CBDCs, which are designed for undertaking interbank transactions and settlements. The concept of wholesale CBDCs is similar to currently available digital assets used for the settlement of interbank transactions, with the key differentiation being the use of technologies such as distributed ledger technology (DLT) and tokenization.

Wholesale CBDCs have garnered global interest with central banks. Facebook’s (albeit failed) attempt to launch its Libra cryptocurrency in 2019 was a breaking point for blockchain technology’s use in global finance, eventually spurring the development of wholesale CBDCs. Initially launched as a measure to counter private cryptocurrencies, wholesale CBDCs are fast emerging as a potential disruptor in the fintech space.

Currently, more than 30 countries are researching the use of wholesale CBDCs. Interestingly, about half of these countries are from Asia. The development of wholesale CBDCs in Asian countries has outpaced the efforts of financially strong economies such as the USA and the UK, as these CBDCs offer more tangible benefits to developing economies in Asia than their more developed counterparts.

Several Asian countries have engaged in pilot programs, and proof-of-concept runs to explore the use of wholesale CBDCs to improve the efficiency of domestic large-value transactions and cross-border transfers.

China has been at the forefront of the development and widespread testing of wholesale CBDCs. Several Southeast Asia and the Middle East countries, including India, the UAE, Thailand, and Singapore, have launched pilot programs to explore the viability of wholesale CBDCs and test interoperability for cross-border transactions.

Achieving faster and cheaper cross-border transactions is key to Asian central banks

Growth in global trade has resulted in exponential growth in cross-border transaction volumes. However, these cross-border transactions are faced with challenges. There may be involvement of potential intermediaries, varying time zones, and regulatory frictions that may cause slower settlement. Financial systems such as SWIFT have a stranglehold on the cross-border transaction ecosystem, with many of these transactions using SWIFT messaging to settle payments.

Potential intermediary fees and forex-related charges also lead to increased transaction costs. According to World Bank’s estimates, transaction costs for cross-border transactions may range up to 6% of the transfer value, a significant surcharge.

Removing friction associated with cross-border transactions is a key goal behind Asian countries’ push toward exploring wholesale CBDCs.

A growing interest in wholesale CBDCs is attracting investments in building large-value payment infrastructures in Asia, allowing for faster and more efficient cross-border transfers. Wholesale CBDCs enable central banks to transact directly with each other, removing the involvement of multiple intermediaries and resulting in quicker transaction settlement. This also results in the elimination of intermediary fees to help lower transaction costs.

Technology also adds elements of security and traceability to these digital transactions. It also offers the potential to program them by automating or restricting payments if certain conditions are met.

Challenging US dollar dominance in cross-border settlements offers additional motivation

Several Asian countries are also looking to reduce their reliance on financial settlement systems that involve US dollar reserves. Currently, most cross-border transactions involve the use of the US dollar. Countries with limited forex reserves also face the challenge of outgoing reserves, resulting in potential currency inflation and adding to the already high transaction costs.

Wholesale CBDCs offer several Asian countries, particularly those with limited US dollar reserves, an opportunity to directly transfer the amount in their local digital currencies and eliminate the need for US dollars in bilateral transactions.

Developing Asian economies, such as China and India, with significant cross-border transactions, are looking to promote their CBDCs as a potential reserve currency in the Asian region that would allow cross-border settlement directly in the digital currency. It is also in the interests of countries such as China to develop its CBDC (e-CNY) as a potential alternative to the US Dollar in cross-border trade to mitigate any potential currency-related challenges posed by economic sanctions from the USA and EU.

What’s Fueling Asia’s Drive to Develop Wholesale CBDCs by EOS Intelligence

What’s Fueling Asia’s Drive to Develop Wholesale CBDCs by EOS Intelligence

Tandem development and collaborations offer tailwinds to CBDC projects in Asia

Central banks of several Asian countries are undertaking information sharing and tandem development of CBDC infrastructures to mitigate some challenges associated with CBDC.

Recent pilot projects such as mBridge, launched by central banks of China, the UAE, Thailand, and Hong Kong, have been testing the use of a common ledger platform for real-time peer-to-peer transactions. The launch of several other projects, such as Project Mandala (involving Singapore, South Korea, and Malaysia) and Project Aber (involving Saudi Arabia and the UAE), is laying the groundwork for the widespread implementation of wholesale CBDCs.

Another potential avenue for collaboration includes forming partnerships with central banks to maintain reserves of digital cash to facilitate direct settlement. China, in particular, plans to develop e-CNY as a potential reserve currency alternative to the US dollar.

Interoperability and ownership are key challenges to CBDC implementation

While the use of wholesale CBDCs certainly comes forward as a boon, there are challenges in using these technology-driven digital currencies. CBDCs may have varying protocols, and interoperability between different CBDC frameworks remains a key challenge for implementing wholesale CBDCs for cross-border transactions.

Establishing common technical and operational standards is essential to ensure CBDC interoperability. Currently, most pilot programs involve CBDCs with common or similar technological frameworks and rules, which limit the application of wholesale CBDCs to a certain number of compatible entities.

Recent research projects are laying the groundwork for CBDCs’ compatibility with various ledgers and technical frameworks. However, significant testing will be required before compatibility can be established across the Asian region.

Ownership, governance, and regulatory oversight of wholesale CBDC technologies are other key concerns. Doubts exist over who will oversee the transactions and ledger entries, especially for any multi-party cross-border transaction.

Systems must also to adhere to anti-money laundering and counter-terrorism financing regulations. Varying financial laws may also hamper the seamless implementation of these anti-money laundering and counter-threat funding regulations across the region.

Lastly, like any digital asset, CBDCs are also susceptible to cyberattacks.

EOS Perspective

Wholesale CBDCs can potentially change the nature of cross-border transactions across Asia and globally.

We are likely to witness significant growth in test runs and pilot programs by several Asian countries to provide proof of concept for the applicability of wholesale CBDCs in countering the challenges associated with cross-border transactions. We can expect a spurt in CBDC alliances and treaties among countries with significant bilateral and intra-regional trade. Simultaneously, it may result in slightly reduced transaction volumes going through existing cross-border financial systems such as SWIFT.

The next stage of CBDC evolution is likely to coincide with the emergence of pilot programs involving multiple CBDCs with different technological frameworks, creating possibilities for easier and seamless cross-border transactions among banks or countries without any existing bilateral or regional partnerships.

These developments are likely to be aided by the development of enabling technologies such as RegTech (regulatory technologies) and SupTech (supervisory technologies), which could provide the sandbox environment for widespread testing of the CBDC systems, as well as lay the groundwork for potential regulatory systems to manage these infrastructures.

With the bulk of cross-border transactions still being conducted in the US dollar, wholesale CBDCs do not pose any imminent threat to its dominance. The US dollar’s future prospects in this role will depend on whether digital currencies such as e-CNY take off as a reserve currency, which is unlikely, at least in the short- to medium-term.

The overall success of wholesale CBDCs will depend on the level of cooperation that countries across Asia can develop over the next few years.

Charting the RegTech Journey – Navigating Consolidation as the Next Vital Phase by EOS Intelligence
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Charting the RegTech Journey: Navigating Consolidation

RegTech, short for regulatory technology and often categorized as a subset of fintech, emerged in 2015. The RegTech industry was fragmented, with numerous small players targeting specific niches within the regulatory compliance landscape. However, the recent trend towards consolidation is reshaping the sector. Larger RegTech firms are increasingly acquiring smaller players to expand their offerings and solidify their market positions.

RegTech comprises powerful tools that leverage advanced technologies such as artificial intelligence (AI), automated machine learning (AML), and big data analytics. These technologies streamline regulatory compliance processes, addressing challenges from technology-driven economies, largely through automation. Automation plays a significant role in reassuring regulatory compliance professionals about the effectiveness and efficiency of RegTech solutions.

According to a 2023 report by Corlytics, a Dublin-based regulatory risk intelligence firm, regulatory penalties associated with legal and regulatory enforcement in the financial sector exceeded US$10.5 billion globally. This underscores the escalating pressure on financial institutions to comply with regulations, prompting them to turn to innovative technological solutions. RegTech has emerged as a promising avenue for organizations within the fintech ecosystem to efficiently navigate complex regulatory landscapes while reducing cost and time and improving compliance effectiveness.

Market landscape transformation through investments and strategic acquisitions

Investors increasingly recognize RegTech’s potential, and it remains a bright spot within the fintech ecosystem. Data from UK-based financial market platform Dealogic shows 116 global RegTech deals in 2023 with a total value of more than US$13.5 billion, demonstrating significant investment activity in the sector. Last year witnessed notable acquisitions across various markets, with larger financial services corporations and RegTech vendors acquiring smaller players to strengthen their market position through consolidation.

Key transactions, such as the acquisition of Adenza by Nasdaq for US$10.5 billion in 2023 and Finellix by Stellex Capital for US$176 million in 2022, underline the strategic importance of RegTech solutions for both financial and technology companies.

These developments reflect a broad strategic move to address the escalating compliance costs faced by banks and brokerages in the wake of regulatory reforms such as the Dodd-Frank Wall Street Reform and Consumer Protection Act (simply known as the Dodd-Frank Act). The Dodd-Frank Act, introduced in the USA in 2010 following the 2007–2008 financial crisis, has had a profound impact on the global financial sector. The Act has prompted financial institutions globally to significantly improve their regulatory reporting systems and processes, leading to more extensive adoption of technology solutions. Dodd-Frank and other stringent regulatory measures have significantly increased compliance costs for financial institutions and companies operating in various sectors.

Larger financial services firms and RegTech companies are consolidating to integrate complementary financial solutions and expand their operations. In one such development, US-based automated RegTech player CUBE acquired UK-based counterpart The Hub Technology in 2023 to further boost their automated regulatory intelligence (ARI) abilities to reduce compliance risk and cost.

Consolidation within the RegTech sector aims to empower larger entities to effectively tackle challenges related to anti-financial crime measures, cross-selling opportunities, and regulatory compliance services, primarily among banking and brokerage clients. This strategy aims to diversify revenue streams, broaden market reach, and increase the serviceable market.

Simultaneously, M&A offers small and mid-size RegTech companies a strategic avenue to enhance capabilities, achieve accelerated growth, better competitive market positioning, and maximize value. While acquisitions often lead to integration within the larger corporate structure, there is still room for acquired smaller RegTech companies to maintain a level of independence.

In 2023, Corlytics acquired the UK-based RegTech firm Clausematch to integrate its capabilities into a comprehensive platform for managing the regulatory risk value chain for tier-1 clients. Despite the acquisition, Clausematch maintains its independence and is a strategic partner to Corlytics. It continues to serve existing clients while also extending its services to Corlytics tier-1 clients, including 14 of the top 50 global banks. This autonomy can be instrumental in fostering partnerships that are essential for scaling up and achieving sustainable growth in the ever-changing fintech regulatory ecosystem that demands agility and continuous innovation.

The appeal of RegTech’s one-stop-shop model

The concept of a one-stop shop model in the RegTech industry, facilitated by consolidation, appeals to businesses seeking streamlined and comprehensive compliance solutions. In the evolving financial market landscape, clients are increasingly preferring to consolidate their RegTech solutions under a single provider rather than engaging with multiple vendors. This demand stems from the desire for streamlined processes, reduced administrative burden, cost savings, and seamless integration of services.

RegTech companies can meet this demand and improve the overall customer experience by offering comprehensive end-to-end solutions and value-added services. In 2023, Muinmos, a Denmark-based RegTech company, saw substantial revenue growth as more clients flocked to the firm. This surge was attributed to Muinmos’ comprehensive platform, which manages the entire onboarding process, spanning from KYC/AML procedures to risk assessments and regulatory classification.

Through strategic acquisitions of smaller RegTech firms with specialized solutions, RegTech solution providers can further enhance their offerings, capitalizing on the trend for integrated solutions and establishing a competitive edge in the market.

Partnerships with smaller firms provide larger companies in the RegTech sector with advantages such as accelerated time-to-market and the opportunity to serve as a testing ground, paving the way for potential future acquisitions.

RegTech startups joining forces

Many RegTech startups are partnering to provide a broader range of regulatory solutions to their clients by enhancing their platforms and adding compatible services from other partners. This forms a robust entity with expanded capabilities to compete with established players.

In November 2023, Flagright, a German-based startup specializing in AML compliance and fraud prevention, formed a strategic alliance with Regtank Technology, a Singapore-based RegTech services provider. This partnership underscores their joint commitment to developing an advanced transaction monitoring solution for fintech companies using AI/ML algorithms. Additionally, these partnerships are likely to help startups reach more customers across various geographies, solving risk and compliance challenges for more businesses.

The double-edged sword of consolidation

For existing and emerging RegTech companies, consolidation presents a double-edged sword. As larger players consolidate and dominate the market, there may be fewer opportunities for investment in smaller, emerging RegTech startups. Investors may perceive greater risk in backing smaller players when larger, more established firms offer similar or more comprehensive solutions. This could lead to a concentration of investment in a few key players, potentially stifling innovation and diversity in the market.

Consolidation impact on the RegTech investment landscape

With fewer startups and a more prominent role for established players, the overall number of investment opportunities in RegTech may slow down in the short term. This could lead to a shift in focus from rapid innovation to the successful integration of acquired technologies as larger players seek to leverage their expanded capabilities and market presence.

Challenges faced by small firms and emerging startups

Consolidation within the RegTech sector could heighten entry barriers for new and smaller firms. Small companies are likely to face resource constraints compared to their larger counterparts. They may struggle to match the scale of investment, R&D capabilities, and market reach of consolidated firms, potentially limiting their ability to innovate and expand their market reach.

Opportunity for small vendors due to consolidation

Consolidation could create gaps in the market for specialized RegTech solutions catering to unaddressed regulatory needs within the RegTech industry. Consolidation efforts in the RegTech sector mainly target large tier-1 clients, including large banks and other financial institutions. However, there are potential gaps and opportunities in smaller businesses across non-financial verticals that require tailored regulatory solutions. This would likely prompt smaller companies to carve out niche areas of specialization within the evolving RegTech landscape.

Specializing in particular regulatory domains, industries, or technological niches allows smaller firms to distinguish themselves as providers of specialized solutions. This makes them appealing targets for acquisition or partnerships by larger players, driven by the ongoing consolidation trends in the RegTech sector.

EOS Perspective

Traditionally, many RegTech companies evolved as single-point solutions for specific regulations. The market is witnessing a shift away from multi-point solutions that address specific issues and moving towards modular solutions that offer flexibility and can be reconfigured to address diverse problems and industry verticals. This shift is likely to drive further consolidation as regulated entities seek mature, cost-effective solutions tailored to their needs.

Conventionally, RegTech solutions have primarily targeted large enterprises with significant budgets. However, we are witnessing a notable shift, as small RegTech companies are now offering affordable compliance solutions tailored to small and medium-sized enterprises (SMEs) as well. This shift is driven by the recognition of unique regulatory challenges faced by different sectors, such as healthcare, insurance, and energy. This recognition prompts small RegTech players to tap into opportunities arising from the growing demand for industry-specific RegTech solutions. This trend reflects a broader movement within the RegTech industry towards democratizing access to compliance tools and addressing the specific needs of diverse business sectors.

With venture funding slowing down due to the economic downturn, a rise in M&A activities is anticipated in the coming years. Due to the time-consuming nature of decision-making around procuring RegTech solutions by regulated entities, major RegTech players are expected to focus on developing and offering sticky RegTech solutions to ensure stable and recurring revenue growth. Consequently, this trend is likely to drive further consolidation within the large RegTech sector, as evidenced by Corolytics’ acquisition of ING SparQ RegTech and Clausematch in 2023, followed by a substantial investment from Verdane, an investment firm, in April 2024. This investment is poised to accelerate Corlytics’ M&A activity, signaling a shift towards the emergence of technology partners that provide unified platforms by integrating solutions from multiple firms through consolidation.

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

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.

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

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.

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