Although the biosimilar space is still growing and evolving in the U.S., it is comparatively well-established in India. According to the Generics and Biosimilars Initiative (GaBI), the first “similar biologic” was approved and marketed in India in 2000 — some 15 years before the U.S. approved its first biosimilar. India also has a much more mature biosimilar manufacturing ecosystem and regulatory environment than most other parts of the world. As such, the country can provide valuable lessons about what it takes to establish a thriving biosimilar market in terms of accessibility, competition, regulatory strategy, and other facets.
For a deeper dive into the Indian biosimilar space, Biosimilar Development posed a series of questions to two industry experts. In this first Q&A, Amy Duval, senior director of biosimilars at Decision Resources Group (DRG), explains what biosimilar developers must do to succeed in this unique market — and what India can teach us about entering other biosimilar markets, both now and in the future.
Are there any particular lessons about biosimilar competition or market dynamics that can be ascertained by looking at India’s biosimilar market?
Amy Duval, Decision Resources Group: There are more non-innovator biologics in India than any other country, a lesson in itself about the number of these drugs a market can support. Non-innovator biologics are often misclassified as biosimilars because they share the same international nonproprietary name, but some have differences in amino acid sequences or high levels of impurities, for example. Because they were not required to undergo comparative clinical testing, it is unproven whether they are indeed biosimilar to the originator brand. Experience from India has shown that non-innovator biologics (and by extrapolation, biosimilars) have the potential to capture high use — some capture up to 75 percent of the available volume share.
The pipeline for biosimilars in India is also robust, in part fueled by the Indian government’s initiative to offer subsidies to Indian biosimilar manufacturers. In Decision Resources Group’s September 2017 analysis, more than 40 biosimilars were in clinical development in India, a similar number to those in development in the European Economic Area (EEA), and far more than in development in the United States.
There are also key lessons around strategy in India. For companies based in major markets, partnering with Indian pharmaceutical businesses may be mutually effective. An example of this is the Apotex (via its European marketing arm, Accord Healthcare) partnership with Intas. This partnership meant that Apotex gained access to Intas’s biosimilars, which have been developed in a cost-effective manner, and that Intas expanded its ability to commercialize its products in Western markets.
Another lesson comes from how the Indian market has driven originator manufacturers to innovate in terms of marketing and partnership strategies. In 2012, Roche withdrew Herceptin from the Indian market but entered into an agreement with India-based Emcure. The agreement allowed Emcure to manufacture and sell the drug in India under the brand name Biceltis, while Roche would market it as Herclon. Both Biceltis and Herclon are sold at a reduced price compared to Herceptin, but are considered as originator biologics in this market. In 2013, Roche relinquished patents on Herceptin in India — the same year the Indian government was considering issuing its first compulsory license for Herceptin, which would have allowed domestic companies to copy the product ahead of patent expiry.
In 2014, Mylan launched Hertraz and Biocon launched CANMab in India. Both of these drugs were considered non-innovator biologics at the time, but earlier this year the companies won a court case allowing them to market these brands as biosimilars in India.
Do any of these lessons apply to biosimilar markets in other nations? How so?
Duval: Factors inherent to the Indian pharmaceutical market have heavily influenced the potential of biosimilars. One of the hallmarks of the Indian non-innovator/biosimilar market, high discounting — which can be well over 50% of the originator brand in some cases — has arisen due to lack of public healthcare coverage and the low income of many patients who need to pay out-of-pocket for treatment. This has driven developers to offer deep discounts in order to ensure their products reach a meaningful number of patients.
In other markets with similar economic environments, the potential for high uptake of biosimilars through aggressive discounting may, therefore, be a transferable lesson. That said, replication of the Indian model elsewhere comes with a caveat — the fact that IP protection in India is notoriously poor and regulatory assessment of biosimilars and non-innovator biologics has not always been thorough. Both of these factors have allowed these classes of drug to rapidly enter the market and have facilitated fast uptake. In markets where IP rights are better protected and/or regulators are more fastidious, the relative ease of biosimilar uptake seen in India may not be replicable.
Notably, many of the factors that have fueled the growth of the India biosimilar market are absent in the major pharmaceutical markets. Therefore, while the Indian model as an example of how biosimilars may successfully penetrate a market, it is not reproducible worldwide. This means that biosimilar manufacturers in other geographies must adapt their strategy based on the most prevalent local market forces.
What should international companies looking to launch biosimilars in India — or partner with Indian companies — keep in mind?
Duval: Price, not clinical data, is the key driver in this market. If a manufacturer is looking to develop a biosimilar where other biosimilars and/or non-originators are already launched, they must price themselves competitively in order to gain a foothold. Moreover, treatment rates with biological molecules are low in India, owing to high cost and the high out-of-pocket expense for patients to access them. While new biosimilar entry has the opportunity to increase treatment rates, pricing will be key, as substantial discounts will likely be required in order to impact the proportion of patients receiving a biologic.
The biosimilar and non-innovator biologics landscape in India is also set to remain competitive. Domestic manufacturers already have a strong presence in this market. This is likely to continue, as the Indian government is offering subsidies to Indian biosimilar manufacturers and funding companies that enter into public-private partnerships (Ministry of Health and Family Welfare, March 2017). For international companies, the requirement to conduct an Indian clinical trial to secure approval is an added logistical burden, but the financial burden of running trials is modest in this market. Partnering with an Indian company may facilitate access and market share for international companies, and furthermore may be beneficial in providing access to biosimilars with lower production costs.
The Central Drugs Standard Control Organization (CDSCO) released a revised biosimilar guidance last year for developers. Are there one or two key takeaways from that guidance that biosimilar companies working with the CDSCO should keep in mind?
Duval: The CDSCO guidance broadly aligns with that of the European Medicines Agency (EMA) and the World Health Organization (WHO). The 2016 update was aimed at reducing the residual risk of clinically meaningful differences between a biosimilar and its reference product through postmarketing studies (specifically, collection of data through a predefined single-arm study conducted within two years of licensing) and additional information with regard to reference product eligibility. So, this guidance introduces more burden on the biosimilar developer to produce head-to-head clinical trials and to meet more robust comparability requirements.
That said, it’s not clear whether these guidelines are strictly adhered to. Some locally developed biosimilars have gained approval without following to this guidance. For example, Hetero Drugs’ Actorise (darbepoetin alfa) was compared to epoetin alfa, not Amgen’s Aranesp (originator darbepoetin alfa), during clinical development (CTRI/2012/07/002835).
Looking five to 10 years down the road, how do you foresee the Indian biosimilar space evolving from a commercialization and/or regulatory standpoint?
Duval: The greatest opportunity in India lies in market expansion. Differential pricing strategies —e.g., offering one very low priced biosimilar to target patients with little ability to pay for treatment and one moderately priced biosimilar to target middle or higher income patients — may be a tactic that some manufacturers take.
For Indian-based developers, the ability to expand their presence beyond the Indian market may be hampered by prescriber trust levels. While price is the main factor of success in the Indian biosimilar market, clinical data, safety, and quality are much more prominent in the minds of prescribers in Western markets. Indeed, Decision Resources Group primary market research indicates that prescribers have much lower levels of trust in manufacturers from markets such as India than in large multi-national manufacturers with a global presence.
To address these issues Indian biosimilar makers could consider partnerships to elevate their profile in other markets. Several Indian companies have entered partnerships with this aim. For example, India-based Biocon has entered a partnership with Mylan. However, by adopting such a strategy, the Indian company also needs to be prepared for increased regulatory scrutiny — Biocon’s Bangalore manufacturing plant has not passed inspections from both the EMA and FDA in 2017.
In our next Q&A, we will hear from Subir Basak, a strategy consultant who helped launch the first Indian biosimilar product in the EU and numerous emerging markets.
About Amy Duval:
Amy Duval, M.Res., is a senior director in the biosimilars team at Decision Resources Group. Ms. Duval manages a team of analysts who conduct extensive primary market research focusing on physician and payer perspectives on biosimilars and secondary market research into the competitive and regulatory landscape for biosimilars. Ms. Duval also provides client support across Decision Resources Group biosimilars products.
Previously, Ms. Duval worked a senior director in the oncology team at Decision Resources Group, where she built expertise in multiple oncology indications including breast and ovarian cancers, and worked on topics in both the major and emerging pharmaceutical markets. Ms. Duval earned her B.Sc. in natural sciences and M.Res. in molecular and cellular biology from the University of Birmingham, where she conducted research into the epigenetics of leukemia.