“Regulations have influenced evolution of biosimilars market”
The biosimilars space continues to evolve rapidly and presents a number of unique challenges and fierce competition. There are many biosimilars in development for some of the top-selling biologicals creating an intense competition amongst the sponsors, especially those wishing to enter the western markets. To avoid any delays, biotech companies need solid clinical development plans built on the latest regulatory guidance with intimate knowledge of the clinical trial landscape. Recently, Priyanka Bajpai from BioSpectrum Asia spoke to Dr Charu Manaktala MD, Head of Asia Pacific Biosimilars Center of Excellence at IQVIA on how companies can design their clinical development plans to meet the western regulators expectations. Dr Manaktala has over 20 years of work experience in the healthcare and pharmaceutical industry and has worked in all stages of clinical drug development from Phase-I through commercialization.
What is the future of biosimilars?
The future of biosimilars is bright – regulatory pathways are becoming clearer and physician acceptance is growing.
For example, the regulatory pathway for biosimilars is well established in the International Conference on Harmonization (ICH) regions and regulatory requirements are becoming more straightforward. To date the European Medicines Agency (EMA) has approved 40 biosimilars for 12 unique biological targets; the US FDA has approved eight biosimilars (post 2010) for six unique biological targets. Further, more than 500 biosimilars for 50+ unique biological targets are reported to be in various stages of development.
Various publicly available market research reports indicate that the biosimilars market will be over $13 billion by year 2024. It is projected that biologics market will exceed $390 billion and account for up to 28 per cent of the global pharmaceuticals market by 2020. The biosimilars market will continue to grow as biologic patents continue to expire in the future.
The biosimilars pipelines and approvals so far were predominantly focused on biological targets with patent expiries around 2020. Some refer to these targets as “Wave I” biosimilars. There are signs that companies are now shifting their focus to the next of biological targets with patent expiries in 2020-2025 and beyond (termed “Wave II” targets).
There are multiple biosimilars in development for any given biological target, with numbers in double digits for some of the top selling products such as Humira, Herceptin, Rituxan /MabThera, Neulasta, Avastin. However, the market may support only a limited number of entrants. Consolidation of the multinational markets is also expected.
Patient and prescriber acceptance of biosimilars is also improving with the emergence of more data.
This indicates a strong future for biosimilars though the exact dynamics on pricing and reimbursement are yet to emerge, especially in the US market.
What role do you see of process innovation and contract manufacturing in its growth?
Biosimilars development is a challenging area as the proposed biosimilars need to demonstrate a high degree of similarity with the innovator biologic in terms of their physicochemical structure, biological
activity, immunogenicity, pharmacokinetics, pharmacodynamics, safety and efficacy. The biosimilars must be developed within that defined design space to match up to the characteristics of the reference biologics.
Technological advances and innovations have certainly helped biosimilars development in many ways such as increase in yield of protein production by employing an innovative feed media; reduction of overall cost of manufacturing process by improving purification techniques and reducing purification steps. These a just a few examples of process innovation that took place since first biological drugs became available on the markets in late 80s.
One important area that is required for biosimilar drug development is mapping out the innovator biologic in terms of its structure, physicochemical properties and biological activity through the demonstration of analytical similarity. The use of advanced analytical techniques for evaluation potency and purity of biosimilars can contribute to streamlining the non-clinical and clinical development. Biologics with better impurity profiles will likely have better safety (& immunogenicity) profiles.
All these innovations could potentially support biosimilars to be more competitive on the price terms and this would be very relevant as some geographies have experienced crowding in this area with multiple biosimilars for a given innovator biologic.
Do you think that regulation can have an impact on how the market evolves? If so, how?
Yes, regulations have definitely influenced the evolution of biosimilars market. For example, the EU regulators paved the way for biosimilars around the globe. In the US, regulations have more slowly evolved and this led to reluctance on the part of some biosimilar sponsors with global aspirations to enter this market.
Current regulations seem to provide a fairly clear pathway for biosimilars development and registration and the current biosimilars regulations create a favourable environment for biosimilar manufacturers.
First and foremost, regulatory requirements for biosimilars are in place in most of the largest markets and the regulatory expectations are becoming more aligned. The regulations rightly recommend the developers to focus on establishing robust analytical biosimilarity as the basis for abbreviated clinical and non-clinical development.
The fact that the guidelines around the world are aligned is a very positive influence as this enables biosimilar developers to have global development programmes that could support marketing authorization in multiple markets at the same time. For example, when the initial guidelines were released it was expected that each regulatory agency would like to see biosimilarity studies against the reference biologic sourced from their own jurisdiction.
However, with the passage of time, and possibly based on requests and feedback from biosimilar manufacturers, the agencies are now accepting that some of the pivotal clinical data could be generated in comparison with reference biologic sourced from another jurisdiction. However, clear and stringent requirements exist for provision of scientific bridging data in support of such an approach.
Similarly, if the agencies in major markets do not agree to have the same endpoint for a pivotal clinical study, it is still possible to have a common study protocol with local amendments/adaptations.
Further many governments and government agencies around the world have been consistently encouraging/recommending/supporting the use of biosimilars over innovator biologics. Some of the notable examples include the French healthy ministry that is encouraging prescription of biosimilars with the target of starting at least 70 per cent of the new biological prescriptions with the biosimilars; England’s National Health Service (NHS) recommendation that at least 90 per cent of new patients should be prescribed the best value biological medicine within 3 months of launch of a biosimilar medicine and at least 80 per cent of existing patients within 12 months; US FDA’s educational initiatives for healthcare providers; and the Norwegian Ministry of Health and Care Services that funded the landmark NorSwitch study to support use/substitution of biosimilar infliximab.
More and more physician expert bodies such as the EULAR, ESMO, ASCO are endorsing biosimilars as viable treatment options. Overall, these are creating a very conducive environment for the biosimilars.
Dr Charu Manaktala
MD, Head of Asia Pacific Biosimilars Center of Excellence at IQVIA