Role of emerging markets
The market penetration of mAbs is limited in emerging markets, largely due to their high cost. Therefore, there is a huge opportunity for biosimilar mAbs in these countries given the size of the market and because there is less competition from branded products in the non-private markets, according to Santos da Silva. Sashidhar also notes that both domestic (e.g., Brazil and India) and international companies are looking to introduce biosimilar mAbs in developing countries where the approval pathways are often less stringent or currently under development. Biosimilar mAbs can be launched relatively quickly in these emerging markets, and companies can gain market experience and market data that can be used for the approval process in developed markets. It also provides a way for companies to more rapidly recoup some of their investment, according to Dingermann.
International companies tend to form partnerships with local pharmaceutical or biotechnology firms to more easily access emerging markets. One such example is the Product Development Partnerships in Brazil, notes Santos da Silva. Another is the collaboration between generic firms Mylan and India’s Biocon on the development of a Herceptin (trastuzumab) biosimilar, which has been approved in India. It should be noted, however, that Roche has filed an injunction against Biocon and Mylan that temporarily prevents them from referring to Canmab and Hertraz as ‘biosimilars of Herceptin’ because Roche claims they were not developed in line with the regulatory guidelines for biosimilars. A hearing is scheduled for February 28, 2014.
Impact of the approval of infliximab
The EU approval of Celltrion’s and Hospira’s mAb biosimilar infliximab (Remsima/Inflectra) is an important milestone in the development of the biosimilar market and for future mAb approvals. The biosimilar was approved for the same range of autoimmune diseases as the branded product (i.e., “extrapolation”), including rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn’s disease (CD), ulcerative colitis (UC), psoriatic arthritis (PsA), and psoriasis. This approval is important not only because it is the first mAb biosimilar approved in a mature market, but also because it included indication extrapolation for all of indications, according to Keeping. “We have not seen an approval for such a wide range of indications based on the results of ‘just’ two clinical trials (RA and AS). Indication extrapolation enables biosimilar developers to achieve significant cost and time savings, which will ultimately have an impact for patients,” she says.
The design of Celltrion’s clinical trials is also worth noting, according to Santos da Silva. “The company conducted a global trial in 20 countries with just 874 patients and clearly designed the study to optimize acceptance by regulators in several different countries around the world.” He adds that the company’s open approach to development of this biosimilar mAb, including many interactions with regulators and leader in the RA field, should set an example for other mAb biosimilar development projects. Celltrion will be launching Remsima in France, Germany, Italy, Spain, and the United Kingdom (the EU5) in 2015, when J&J’s recently won patent extension for Remicade elapses in February of that year.
Achieving acceptance
Getting approval for a mAb biosimilar does not guarantee success, however. Biosimilar manufacturers must first convince physicians, pharmacists, and patients that biosimilar mAbs are safe and effective. “Acceptance of biosimilars is highly variable from country to country and depends on the molecule type and indications,” notes Keeping. Biosimilar erythropoiesis-stimulating agents and granulocyte colony-stimulating factors (G-CSFs) that are available in Europe are used in oncology indications, so oncologists are potentially more familiar with them and receptive to new products. Many mAbs, however, can also be used for other indications, such as respiratory disorders, according to Sashidhar. He believes, therefore, that biosimilar mAbs will be more likely to be accepted initially in regions where the emphasis is on low-cost drugs.
“There are definitely reservations among physicians and pharmacists in the EU, and it is up to biosimilar manufacturers to educate them, which will require improved marketing efforts,” asserts Dingermann. Strong government support that encourages the uptake of mAb biosimilars, together with strong clinical data (such as for G-CSFs), is also needed, according to Santos da Silva.
Recent activity and future expectations
In addition to its approval in the EU, Celltrion has received approval for Remsima in South Korea and Canada, and has applied for approval in Japan. The company also received approval in South Korea in January 2014 for its second biosimilar mAb Herzuma (trastuzumab). In India, Intas Pharmaceuticals launched its rituximab biosimilar of Rituxan (Genentech/Biogen Idec) in May 2013. Biocon received approval for CANMAb (trastuzumab, developed with Mylan) in November 2013 and announced the launch of the product in January 2014. Dr Reddy’s Laboratories and Intas Pharmaceuticals are also developing trastuzumab biosimilars for the Indian market. It should be noted that there is a debate as to whether these products should be considered biosimilars.
Notably, most major international pharmaceutical companies are developing biosimilar mAbs, including Pfizer, Amgen, Merck Serono, and Boehringer Ingelheim. Leading generic-drug firms, including Sandoz, Mylan, and Teva, are active in this area as well. As a result, analysts expect that several additional mAbs will be approved in both developed and emerging markets over the next several years, which should, if they are accepted, contribute to significant growth of the biosimilars market.
About the Author
Cynthia A. Challener is a contributing editor to BioPharm International.