Key cautionary drivers may include the cost of bringing a biosimilar to market, estimated to be about $10 million to $40 million (some estimates put costs at between $75–250 million per molecule) with a time frame of six to nine years, compared with $1 to $2 million and three years for generics. And since biosimilars are produced in living systems and inherently far more complex than generic small molecule drugs, regulators require concomitantly rigorous steps, product testing, and approval.
As the industry awaits a range of biologics U.S. patents to expire including Amgen’s Neupogen in 2013, Biogen Idec’s Avonex in 2013, and Genentech’s Herceptin in 2014, remaining uncertainties about how regulatory agencies will ultimately regulate biosimilar commercializations persist.
Regulatory uncertainty may be reflected in Teva’s and Lonza’s October 2012 discontinuation of their planned 544-patient, Phase III clinical trial of a Rituxan biosimilar, saying they wanted to get input from regulators on how to design the trial program. At the time, Teva said it remained firmly committed to the development of biosimilars. However, the company said, given the changes in the regulatory and competitive environment, “Teva (through its joint venture with Lonza) is evaluating the path forward for rituximab.”
According to the story originally reported in the Israeli newspaper Haaretz, Teva halted the trial while it ponders the best path to a regulatory approval in Europe, where patent protection lapses this year and in the U.S. in 2018.
Samsung bailed on its Rituxan program in October 2012, with an unnamed source telling a Korean newspaper that the company stopped clinical development of SAIT101—the biosimilar version of the Rituxan because of "some internal reasons," with speculation that recent regulatory guidelines from U.S. regulators could be partly to blame for the delay.
Its patent due to expire in 2013 in Europe and 2018 in the U.S, Rituxan (MabThera) was an early target of biosimilar manufacturers, and several companies began scrambling to produce their own versions of the biologic. With estimated 2012 revenues totaling $6.94 billion worldwide, Rituxan 2011 revenues grew by 7% year over year excluding currency fluctuations, accounting for 15% of Roche's overall sales for the year.
Companies still in the Rituxan race include Sandoz (Novartis’ generic unit), which is currently conducting a Phase I/II trial testing its biosimilar GP2013 in rheumatoid arthritis and a Phase III trial in patients with advanced folicular lymphoma.
Others include Pfizer with its PF-o5280586 for rheumatoid arthritis and NHL, Merck with MK8808 in RA patients, as well as South Korean Celltrion in a joint venture with Hospira, testing CT-P10 in a Phase I trial for RA and another Phase I for lymphoma.