Biopharmaceuticals and Biosimilars
Market Trends and Future Prospects
Gillian Woollett, MA, DPhil, VP and Head of Regulatory Strategy and Policy, Samsung Bioepis
Christopher Conway, President, Curia
Dear Readers, Welcome to our panel discussion on Biopharmaceuticals and Biosimilars: Market Trends and Future Prospects. Our esteemed panelists, Gillian Woollett and Christopher Conway will share their expertise on regulatory strategies, market dynamics, and innovative trends shaping the Biopharmaceuticals landscape. Join us as we delve into the evolving world of biopharmaceuticals and biosimilars, exploring insights that promise to shape the future of Pharma Industry
1. How do biopharmaceuticals and biosimilars impact healthcare costs and patient affordability?
Gillian Woollett:
• Biologics have become mainstay treatments for many chronic and acute diseases, becoming increasingly fundamental in reducing mortality and managing multiple medical conditions. However, access to these treatments can be limited, often due to high cost of treatment or lack of necessary infrastructure.
• In the EU, biologics represented 40% of the total expenditure in 2022 which has significantly increased compared to that of 2012 (28%) and this is expected to grow due to increased utilisation of biologics as advanced established treatments, and due to the introduction of new biologics.
• In the United States, the biologics market has grown 12.5% on an annual basis from 2017 to 2021 and now comprises 46% of prescription medicine spending. As more novel biologics are introduced, the percentage of biologics spending is expected to rise over the years in the US too.
• Biosimilars, as lower cost alternatives, play an important role in alleviating the financial burden faced by healthcare systems, as well as by increasing surety of supply. In the US, the past five years’ savings due to biosimilars has been estimated to be $40 billion (compared to the anticipated spending without biosimilar competition over the same period). Similarly, estimates suggest there is up to $180 billion of potential savings from biosimilars between 2023 and 2027. In Europe, the cumulative savings from biosimilars are estimated to be over €30 billion since the introduction of the first biosimilar in 2006.
• Biosimilars also play an important role in improving the quality of care for patients. When patients do not have timely access to biologic medicines, it can significantly impact their disease progression in an irreversible manner. This is particularly important for the often debilitating, progressive, and fatal diseases treated by biologics. However, the introduction of biosimilars frequently causes higher utilisation of the molecule as lower costs offer increased access to more patients (e.g., UK with filgrastim).
• Access to quality and timely medical care will continue to be an issue for many countries around the world as more novel biologics are introduced, and biosimilars will play an increasingly vital role in allowing earlier access to these life-enhancing biologic treatments.
2. What role do regulatory agencies play in ensuring the safety and efficacy of biopharmaceuticals and biosimilars?
Christopher Conway: Regulatory agencies play two key parts in ensuring the safety and efficacy of biopharmaceuticals and biosimilars:
1. Science based evaluation of the new proposed product, and further evaluation of any changes which occur during the lifecycle of the product
2. Initial and ongoing surveillance of the pharmaceutical supply chain, including manufacturing facilities to ensure they meet cGMP requirements
The evaluation of biosimilars is more complex than that of generic small molecules – requiring the manufacturer to be able to defend science-based questions on their product which they would not experience with small molecules.
3. What are the key differences between regulatory pathways for biosimilars and small molecule drugs?
Gillian Woollett: The goal of a subsequent version of a previously approved medicine is to match the clinical outcomes of the original through offering quality, safety and efficacy without requiring a complete, new development programme. For generic drugs this can usually be achieved based on the known molecular structure of that original medicine, but for biologics it can be more complicated because biologics are made in living systems and often represent complex mixtures. Fortunately, extensive experience has been accumulated with the originator products by the time biosimilars are developed, and often with manufacturing changes to those products (the so-called comparability exercise) which enables sponsors and regulators to used state-of-the-art technology to measure what matters most to those clinical outcomes. This is particularly true of the class of biologics known as monoclonal antibodies.
For a generic product to be approved, in the US, the sponsors must demonstrate that the active ingredient, dosage form, route of administration, and strength are the same as the reference small molecule drug. Analytical characterisation and bioequivalence test are required to demonstrate that the generic product performs in the same manner as the reference product. However, the in vivo bioequivalence studies can be waived in some cases depending on the site of action, route of delivery, dosage form, and formulation design. Such bioequivalence studies are routinely waived for injected products.
For a biosimilar, the sponsor needs to demonstrate that the biosimilar product is highly similar to the reference product and has no clinically meaningful differences in terms of safety, purity, and potency. This has, to date, entailed a lot more than bioequivalence studies and routinely involved multiyear extensive comparative clinical efficacy studies. However, we now have the opportunity to revisit the highly successful experience with biosimilars approved already that shows that analytics are the fundamental and most sensitive basis for judging biosimilarity. Plus, significant progress is being made in analytical science and its ability to detect differences, and this allows a reduction in the clinical study expectations with no change in the quality, safety and efficacy of the biologics ultimately approved. This uses the same regulatory science established with comparability by FDA in 1996 for originator biologics, as also adopted by EU in 2003, and subsequently as part of the global harmonising body ICH as the guideline ICH Q5E. ICH guidelines offer support for the quality for all medicines worldwide.
Christopher Conway: The generic small molecule and biosimilar pathways differ dramatically because within the small molecule world, it is possible to exactly duplicate the target compound. With biosimilars, it is not possible to exactly duplicate the target molecule, and therefore, additional studies are needed
With small molecule generics, substitutability is a given; however, with biosimilars, it is not. A specific class of interchangeable biosimilars requires additional studies and evidence to be considered directly substitutable at the pharmacy level.
Many generic small molecule products do not require clinical studies for approval; however, for biosimilars, clinical studies are a given, meaning more complexity and cost, leading to longer lead times to market versus their small molecule counterparts.
4. How do regulatory changes, such as the introduction of biosimilar naming conventions, affect market dynamics?
Christopher Conway: In its simplest form, biosimilar naming conventions impact adoption by pharmacists. The current convention involves using a nonproprietary base name (similar to the originator biologic) along with a designated suffix unique to each biosimilar. Pharmacists would be more confident to use the biosimilar interchangeably with the originator if both have the same name. Something as seemingly simple as the naming convention has a dramatic impact on adoption, which ultimately impacts price, market share, and most significantly, competitive dynamics.
5. Are there any specific regulatory challenges in gaining approval for complex biologics and biosimilars?
Gillian Woollett: Biologics, including biosimilars, face a multitude of regulatory challenges, and the biggest issue becomes their being treated inconsistently with each other and across markets. Ultimately no patient can access a product if it is not approved for use by their country and if their health care system does not support access. Legal, regulatory and economic factors matter. The science is largely asked and answered and the same worldwide.
Economics considerations often predominate. Biosimilars stimulate market competition and lower the average price of the molecule, thereby increasing access. Further, the savings from biosimilars can be reinvested to improve quality of healthcare as well as for use of the next generation of improved medicines, including biologics.
It is estimated that 70% of originator biologics could face biosimilar competition in the future, but nearly half of them (47%) have no biosimilars in development. This illustrates the challenges to sustainability for biosimilars, and needs to be addressed with some urgency. Streamlining development, and global harmonisation can facilitate the availability of quality-assured, safe and effective biosimilars to many more patients. There is an international regulatory initiative underway to consider this and it can greatly facilitate access by low- and middle-income countries as well as traditionally leading markets such as the EU and US. Creating regulatory predictability, through removing the expectation of comparative clinical studies that contribute no new information for regulatory decision-making purposes, could rescue some of the potential for competition.
If there is not enough competition from biosimilars, it will ultimately have a negative effect on the sustainability of the biosimilar market and the viability of the biologics market overall. Lack of competition precludes access to the latest originator biologics because the older biologics will continue to consume available funds. The virtuous cycle becomes stalled and patients suffer unnecessarily.
From sponsor’s perspective, improving the efficiency of biosimilar development (reducing both cost and time) is essential, and it is already major priority in the US with the FDA’s pilot research programme funded by BsUFA III. There are also active debates ongoing between global regulators and sponsors about regulatory streamlining:
- No unnecessary clinical comparator studies (e.g., implementation of the MHRA, WHO Guideline).
- Regulatory convergence (EU Term)/ harmonization (US term) to enable one data set to be used in multiple jurisdictions, with no repeats in specific studies, when the reference product is known to be the same.
- Regulatory reliance to reflect previous reviewer evaluations enables more timely approvals as there is then no need for repeated evaluations of the same date by each regulator in every jurisdiction
Recognition of a global comparator product when there is clear evidence that the originator biologic used as the reference is already the same in different markets so a biosimilar should be able to be too. This may include public information from regulators own websites, such as FDA and EMA that shows that the reference products themselves were approved based on the same pivotal clinical studies in both jurisdictions and therefore must be the same product.
The science supports the more efficient approach, and the regulators largely agree, so the issue is expediting the process to achieve such efficient regulation that retains the feasibility of biosimilar development for multiple sponsors in multiple jurisdictions as soon as possible. Absent regulatory predictability and science-based, consistent, regulatory decision-making competition is likely to stall.
6. How do market access strategies differ between developed and developing regions for biopharmaceuticals and biosimilars?
Gillian Woollett: Different countries have different health priorities, and different levels of resources to spend addressing them. While medicines, including biologics, are very important, their appropriate use depends on other infrastructure, such as access to health care providers and hospitals, as well as timely diagnosis of disease for which effective therapies are available. Consequently, different therapeutic areas are being addressed very differently in various jurisdictions.
WHO plays an important role in helping countries access affordable essential medicines, and also in facilitating collaborative approaches to their review and approval. WHO is very involved in access to both generic and biosimilar medicines because their affordability is key to access and they represent 80-90% of the doses that ultimately reach patients.
One challenge is when a country does not have the reference medicines, can they access a biosimilar? That again entails local decisions by the country concerned.
Biosimilars sponsors would like to make their quality-assured, safe and effective medicines available as broadly as possible, but this requires market access, procurement as well as the necessary healthcare infrastructure to be available too.
Christopher Conway: Market access strategies for biopharmaceuticals and biosimilars vary significantly between developed and developing regions. Factors such as treatment rates, regulatory environments, and affordability all impact access strategies. For these reasons, companies need to tailor their go-to-market and commercial models to each individual region’s unique characteristics. This can prove to be quite challenging and often financially unsustainable.
7. What impact do intellectual property rights and patent expiration have on the biosimilars market?
Christopher Conway: As with small molecule products, patent rights play an important role in determining when a biosimilar may enter the market. The Biologics Price Competition and Innovation Act (BPCIA) sets forth a process whereby branded pharmaceutical companies identify relevant patents and potential competitors (biosimilar manufacturers) challenge those patents. If the challenge is successful and the patents are found to be invalid or not infringed, the biosimilar can enter the market earlier. If the patents are valid and infringement is demonstrated, then the biosimilar cannot enter the market until after the relevant patents have expired.
8. Can you discuss the role of real-world evidence and post-market surveillance in ensuring the safety and effectiveness of biopharmaceuticals and biosimilars?
Gillian Woollett: As with any medicines approved by stringent regulatory authorities, pharmacovigilance is an important part of the life-cycle of biopharmaceuticals, including biosimilars, to ensure continuous safety and effectiveness after introduction into the market. For those countries with established PV systems, they apply to biosimilars in the same manner as any other medicine.
Biosimilars are behaving as expected, namely giving the same clinical benefit as their reference originator products, and confidence in analytics that support the approval and continued manufacturing of quality-assured biologics is increasing. No unusual or expected adverse events have been seen with biosimilars anywhere and that supports their global use. Demands for real-world evidence (RWE) and big data are increasing and global for all medicines, and data integration becoming more feasible.
Nonetheless, while sponsors are ready to streamline development they need regulatory predictability to invest in more biosimilars and subsequent markets: for instance, reducing studies that offer no new information such as comparative efficacy studies, using experience and data accumulated with the same products in other jurisdictions, such as RWE, and facilitating regulatory reliance globally through regulatory norms such as WHO can all expedite broader access everywhere. Such approaches share the costs across more patients and make economic sense for everyone.
9. What are the key factors influencing physician and patient acceptance of biosimilars?
Gillian Woollett: The science and core regulatory requirements are the same for every biosimilar irrespective of the therapeutic area, but the understanding by health care providers has to be revisited each time a new physician and patient population is given the opportunity to use them. Fortunately, leading regulators including FDA and EMA, have become more involved in education, working on educational materials, including supporting Continuing Medical Education Credits. It is an on-going challenge, because they have a lot of stakeholders to reach, and many health care professionals have little time and are already familiar with the reference product and have little incentive to change. Biosimilars sponsors also have to take on a role to ensure that all stakeholders fully understand that biosimilars will give the same clinical results as their reference products and are approved to the same quality, safety and efficacy standards as their reference products by the same regulatory authorities.
Christopher Conway: These factors do not differ too much from the factors that influence both physicians' and patients' acceptance of any prescribed product. Safety and efficacy are, of course, critical, but it does not end there. Physician prescribing habits, patient affordability, and, generally speaking, the level of knowledge all have an impact. The better we can educate, the more apt both patients and physicians will be to make informed decisions. Otherwise, other factors like lack of confidence in regulatory pathways and naming conventions will have a much greater impact.
10. How do healthcare systems balance cost savings with maintaining therapeutic options for patients through biosimilar adoption?
Christopher Conway: There are many factors that come into play here, which makes striking this balance difficult. Healthcare systems must strike a delicate balance by leveraging evidence-based practices, optimizing resources, and embracing technology to achieve cost savings without compromising patient care. The ability to achieve this balance is widely variable
11. Are there any specific therapeutic areas where biosimilars are expected to have a significant impact in the near future?
Gillian Woollett: While biosimilars have been widely utilised in therapeutic areas of immunology and oncology, the use of biosimilars has expanded to various therapeutic areas including ophthalmology, endocrinology, and haematology. Biosimilars are expected to have a significant impact on therapeutic areas where there was no biosimilar competition previously especially for rare diseases. Essentially a biosimilar can be made to any previously approved biologic, but the market conditions do vary.
Across the industry, there are ongoing developments for the immunology pipeline including ustekinumab, golimumab, certolizumab pegol, and tocilizumab (just to name a few) as these medicines are expected to lose exclusivity within the next few years. There are also a number of biologics such as aflibercept, denosumab, and eculizumab that are expecting competition from multiple biosimilar companies. Commercial decisions govern once the science and regulatory issues are resolved.
Christopher Conway: Biosimilars are on track to continue their double-digit growth globally, with the market projected to reach over $30 billion by 2025 and $60 billion by the end of the decade. In order to achieve that rate of growth, they will no doubt impact a wide range of therapeutic areas including but not limited to Oncology, Diabetes, and Arthritis.
12. As newcomers to Pharma Focus Europe magazine, could you share how your contributions have enriched our understanding of biopharmaceuticals and biosimilars, and how you envision your insights benefiting our readership and the industry as a whole?
Gillian Woollett: The long-term viability and sustainability of biosimilars is not guaranteed. There is a need for biosimilar awareness translated across therapeutic areas, as well as products, to increase biosimilar development and utilization more expeditiously. The goal is now and always will be to lower healthcare costs with no compromise in the quality, safety and efficacy of the biologics available to patients. Education by regulators especially, but also individual companies will continue to be important.
Christopher Conway: The majority of the population has an “outside-in” view of this world. Having been in the industry for the last 20-plus years, I am fortunate enough to have a “peek behind the curtain,” which affords me the ability to provide a unique perspective.
Thank you to our panelists for their insights on Biopharmaceuticals and Biosimilars: Market Trends and Future Prospects. We hope these discussions have provided valuable insights into the evolving Pharmaceuitical landscape.
Author Bio
Gillian Woollett, MA, DPhil, is responsible for providing science-based regulatory strategy and policy expertise for biologics, including biosimilars, at Samsung Bioepis. She currently chairs the International Generic and Biosimilar Association’s (IGBA) Biosimilars Committee, working closely with World Health Organization (WHO) on access and affordability matters.
Chris is a seasoned business executive with 25 years of experience across aerospace, pharmaceutical/biotech, and contract research and manufacturing. He has extensive expertise in P&L leadership, sales, and marketing in both public and private equity-backed companies. Currently, Chris is the President and R&D Business Unit Head at Curia and serves as a Director on the boards of Viyash Life Sciences and the Drug, Chemical & Associated Technologies Association (DCAT).
