On February 22, 2017, the European Commission (EC), following the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) positive opinion, approved Celltrion’s Truxima (rituximab biosimilar), a significant milestone in the European biosimilars market.  Truxima is the first EC-approved monoclonal antibody biosimilar for oncology (and the second for immunology). The EC approved Truxima for use in all the indications that Roche’s MabThera is approved for, including non-Hodgkin’s Lymphoma (NHL), chronic lymphocytic leukemia (CLL) and rheumatoid arthritis (RA).

The clinical development of Truxima has been quick (initiated in 2012), and straight forward. Safety, efficacy, pharmacodynamics, and pharmacokinetics were evaluated in Phase I and Phase III trials in both NHL and RA patients. Given the issues with extrapolating efficacy data from RA to NHL (and vice versa), this was a wise (and probably necessary) strategy from Celltrion, to ensure that Truxima was approved for all of MabThera’s indications.

Truxima, is the first rituximab biosimilar to enter the global market, but is expected to be joined by others in the future. In total, Decision Resources Group has identified 14 rituximab biosimilars in clinical development (and many more in pre-clinical development), the majority of which are positioned towards the major markets. With a first to market advantage, and a proven track record in Europe in marketing biosimilars (Celltrion’s infliximab biosimilar is marketed in Europe [under Remsima and Inflectra] since February 2015), Celltrion is in a prime position to capture a significant portion of the European, if not the global, biosimilar rituximab market.

The importance of this approval, and subsequent launch is multifaceted:

  • Rituxan/MabThera is a multibillion-dollar drug; Roche reported global sales of CHF 7.3 billion in 2016, approximately a 3% increase from 2015. The majority of sales are attributed to use in the oncology space — almost 80% of total sales. Importantly, a quarter of Rituxan/MabThera’s sales are generated in Europe (CHF 1.9 billion). The sheer magnitude of Rituxan/MabThera’s sales point directly to the importance of Truxima’s approval. Rituxan/MabThera represent a significant cost for healthcare systems and payers globally, and indeed in austerity-hit and cost-constrained Europe, making biosimilar rituximab a very attractive option, the uptake of which will help in containing healthcare expenditure.
  • Truxima is the first oncology monoclonal antibody biosimilar to enter the market. While oncologists, especially in Europe, are familiar and comfortable with prescribing biosimilars, they have only been exposed to biosimilars of relatively simple biologics (filgrastim, a recombinant protein, biosimilars have been available since 2008 in Europe). Research conducted by Decision Resources Group indicates that oncologists are on average more cautious about monoclonal antibody biosimilars versus those of recombinant proteins. Regardless, we find that oncologists are the most accepting of biosimilars among the specialties we survey, something that is also evident, for example, by the historical uptake of filgrastim biosimilars in Europe versus erythropoiesis alfa biosimilars. Taken together with payers pushing towards use of generics and biosimilars, we expect that hematology oncologists will readily prescribe rituximab biosimilars shortly after becoming available, quickly eroding Rituxan/MabThera’s patient share and sales potential.
    • Of note, a subcutaneously (SC) administered alternative to MabThera is currently marketed in Europe (MabThera SC), which is patented and thus protected from biosimilar erosion. Roche’s strategy to develop and transition patients to a more conveniently administered MabThera formulation will limit the sales potential of rituximab biosimilars, which are administered by intravenous infusion only. In a move to protect Rituxan sales in the United States, Halozyme and Genentech/Roche recently submitted an sBLA for Rituxan SC with the FDA.
  • Finally, Truxima will pave the way for future monoclonal antibody biosimilars. By prescribing Truxima, hematology oncologists will generate invaluable data, through post-marketing studies and safety monitoring, that could in turn be used by biosimilar developers of other reference molecules to argue that monoclonal antibody biosimilars are as safe and efficacious as the reference brand, and are not detrimental to the health and life expectancy of cancer patients. In the near-term future, biosimilars of Herceptin (CHF 6.8 billion in 2016) and Avastin (CHF 6.8 billion in 2016) are also expected to be approved in the major markets, representing another significant commercial opportunity for biosimilar developers. While medical oncologists will not have direct experience with prescribing rituximab biosimilars, it is expected that the experience of hematology oncologists will translate to greater uptake of trastuzumab and bevacizumab biosimilars, compared with rituximab biosimilar uptake, perhaps offering better return for investment to developers of emerging trastuzumab and bevacizumab biosimilars.

Truxima, and rituximab biosimilars, are expected to have a significant impact to Rituxan/MabThera sales in the major markets. Decision Resources Group forecasts an annual reduction in Rituxan/MabThera IV sales of approximately 15%. In contrast, rituximab biosimilar sales will grow rapidly, owing to robust uptake by hematology oncologists, and will account for approximately three quarters of the rituximab market by 2025. Importantly, monoclonal antibody biosimilars for oncology indications are expected to be the second-leading biosimilar drug class in 2025, accounting for approximately a third of biosimilar sales, and saving major market healthcare systems almost $9 billion. For more information, please refer to Decision Resources Group’s Biosimilars content, or contact us at Questions@TeamDRG.com.

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