The first biosimilar agent for Lucentis (ranibizumab, Genentech) has come to market in India with the launch of Intas Pharmaceuticals’’ Razumab in June. But whether biosimilar agents gain any traction in the United States remains to be seen as they must overcome myriad regulatory and competitive hurdles.
Biosimilars are to branded biologic agents like Lucentis what generics are to branded small-molecule drugs.
The biosimilars sector may have received a boost earlier this year when Sandoz’s Zarxio (filgrastrim) became the first biosimilar agent the Food and Drug Administration approved via a streamlined application process enacted in 2009. However, a number of challenges lie ahead before the hundreds of biosimilar agents in the pipeline come to market in the United States, according to speakers at the Biosimilars 20/20 conference last month in Philadelphia.
The FDA approved Zarxio for all the indications of its reference biologic, Amgen’s Neupogen, a granulocyte colony-stimulating factor (G-CSF) approved for five different indications ranging from chemotherapy-induced neutropenia to severe chronic neutropenia. Giving a biosimilar all the indications of its index biologic agent is a concept known as full extrapolation, but that is no longer a given for biosimilars, Steven Miller, MD, MBA, senior vice president of Express Scripts, said at the conference. “A couple of months later, we no longer have full extrapolation,” he said.
And despite the biosimilar-specific FDA pathway, established with passage of the Biologics Price Competition and Innovation Act (BPCIA) of 2009, the regulatory process is still fraught with uncertainty, according to Gillian Woollett, MA, DPhil, senior vice president for Avalere Health and former vice president of the Pharmaceutical Research and Manufacturers of America (PhRMA). “The FDA expects to approve 11 biologics this year,” she said. “If the FDA continues to approve at a rate of 11 biologics a year, with nearly 1,000 in development (already in clinical trials), it will take 100 years to get those in the pipeline today approved.”
Specifically in ophthalmology, and specifically for Lucentis, the windows may be closing for biosimilar competitors in the United States. Two companies, Pfenex and Apotex, are working to develop a biosimilar form of Lucentis for the U.S. and European markets, according to Ronny Gal, an analyst at Bernstein who follows biologics. Lucentis comes off patent in the United States in 2020 and in Europe in 2022, said Gal. But copying ranibizumab may be a risky venture for biosimilars developers because of “clinical obsolescence” of the index biologic, Gal said.
Intas is also the only company from India to have launched a biosimilar in the highly regulated European market and is also the only company from India to have two of its biosimilars filed for registration in the United States. The company expects to launch its first biosimilar in the United States within the next 12 months.