Dr Charu Manaktala, Senior Medical Director & Head of Asia Pacific Biosimilars Centre of Excellence, Strategic Drug Development, QuintilesIMS Asia
EMA has approved 25 biosimilars and another 3 have received positive opinion from the CHMP as of December 2016,2 US FDA has approved 4 biosimilars till date via the 351(k) pathway. In addition, a number of biosimilars have been approved in other highly regulated markets of Japan, Canada, Australia and South Korea.
For the years to come, we expect a steady stream of biosimilar approvals to continue, with wave 2 biosimilars (for biologics with patent expiries between 2015 and 2020) dominating. This is a reflection of the fact that these products have been biopharmaceutical industry’s top grosser for the last few years. While we do see signs of development of 3rd wave biosimilars (i.e., for biologicals with patent expiries beyond 2020), however, this is at best sparse, and still quite some time away from regulatory approvals. 2017 could see approval of trastuzumab, rituximab and bevacizumab biosimilars in the EU &/or US.
Evolution of The Regulatory Framework
2016 marked the 10th anniversary for approval of the 1st biosimilar in the EU. By this time the basic regulatory framework for biosimilars registration has been established fairly well. A number of regulatory guidelines are in place as well as a good amount of experience has been gained on a number of biosimilars ranging from simple proteins to complex monoclonal antibodies. Some of the other highly regulated markets such as Japan, South Korea, Canada, Australia among others have adopted EU biosimilar guidelines to a large degree. In addition to the revision of some of the earlier guidelines, the EMA published guidelines for pharmacovigilance of biologics in 2016. The US FDA has published a guidance on the labeling of biosimilars in March 2016.
The naming of biologicals and interchangeability of biosimilars continue to be hotly debated topics. The EMA has approved biosimilars under the same non-proprietary name as for the reference product. In 2015, the US FDA issued draft guidance on the subject of the non-proprietary naming of biosimilars. This guidance recommends that all biologicals should have non-proprietary names that include a four-letter suffix to distinguish them from each other. The suffix would be composed of four lowercase letters and not carry any meaning. The proposed approach is intended with a view to clearly identify biological products to improve pharmacovigilance, and, preventing any unintended substitution. However, a number of industry stakeholders, including the USP have requested for alternative approaches to be considered.
While the interchangeability guidance from the US FDA is awaited, Sandoz recently reported study findings that show lack of safety and efficacy impact from multiple back and forth switches between the etanercept biosimilar and the originator product.
Also, we expect to see more products obtaining marketing approval on the basis of lean clinical data packages (especially where validated PD markers are available), supported by strong quality comparability, in vitro biological activity evidence and clinical PK-PD studies.
Market Uptake of Biosimilars/Realization of Biosimilars Potential in Expanding Access and Saving Healthcare Budgets
A complex interplay of biosimilars versus originator pricing, stakeholder awareness and attitudes is going to play an important role in shaping the future of biosimilars. The EU experience with biosimilars over the last 10 years has been quite positive with a definite cost saving as well as the expansion of treatment access (as well shaping a change in treatment paradigms). Further, the EU experience with the marketed biosimilars has not revealed any unexpected untoward efficacy or safety concerns in the real world use setting.
Published studies and systematic analyses provide further evidence supporting the safety and efficacy of biosimilars, including experience in the setting of single and multiple switches between biosimilar and originator (notably NorSwitch and EGALITY studies). Such emerging data is likely to contribute towards building the confidence of the prescribers, patients, and payers in the biosimilars, and this is likely to impact the biosimilars uptake positively. In fact, we see more and more expert bodies around the world endorsing the use of biosimilars now. Recent surveys reveal that physicians’ knowledge about biosimilars is improving but still there remain knowledge gaps. These findings affirm the need for further focus on prescriber and patient education regarding the biosimilars.
Market Consolidation
2016 has seen at least two significant players exiting/considering to exit the biosimilars domain in favour of their other priorities. In the months following the Shire-Baxalta merger, Shire returned the rights to two biosimilars that Baxalta was developed jointly with other companies, adalimumab biosimilar with Momenta Pharmaceuticals and etanercept biosimilar with Coherus BioSciences. Recently, Merck KGaA was also reported to be re-evaluating its biosimilars business. It will be no surprise if we see further consolidation in this space in the years to come. The biosimilars development pipelines are crowded and the area is highly competitive. The market may be able to sustain only a limited number of players ultimately. So only those who have the long term focus will remain. Given the nature of biosimilars business, partnerships will continue to play an important role in this domain.
Spurring Innovation
Originators have responded to the impending biosimilars challenge with a combination of strategies that prominently include an extension of patents, patent litigation, dropping prices, developing newer formulations or obtaining additional indications for existing biologics, developing their own biosimilar assets, or developing bio-better or next generation products. Most importantly, the competition from biosimilars is an important driver for innovation, paving the way for newer therapeutic options and thus influencing patient outcomes positively.
Biosimilars Development in Asia
Asian manufacturers, especially from South Korea, continue to be significant players in the current biosimilars landscape, with rich product pipelines as well as a number of approved products in both the EU & US.
South Korea is reported to have a goal of controlling 22 percent of the global biosimilars market by 2020. This goal is supported by the Korean government by way of providing capital as well as regulatory assistance to the biopharmaceutical companies.
A number of Asian companies are now looking at entering the global markets, and seem to be adopting global development strategies right from the outset instead of their earlier approach of developing products for local/regional markets first followed by the Western markets. Indian Central Drugs Standard Control Organization (CDSCO) guidelines for biosimilars were revised recently.
Note: References available on request.
