Testing an Accelerated Path for Biosimilars

By Bio-IT World Staff

July 28, 2014 | Since the passage of the Affordable Care Act in 2010, a streamlined regulatory path has been available in the U.S. for biosimilars: generic versions of biologic drugs, such as proteins and RNA complexes, manufactured through living systems like bacteria or viruses. Biosimilars are not like ordinary generic drugs, which can be chemically identical to the pharmaceuticals they copy; small differences in the cell lines used to produce biologics can lead to real differences in their safety and efficacy. However, regulators have judged that holding biosimilars to the same clinical rigor as completely novel drugs creates redundant effort, and could drive up the price of biologics even after their original patents expire. Nevertheless, the provision of the ACA that allows the FDA to give expedited consideration to biosimilars, known as the Biologics Price Competition and Innovation Act (BPCIA), has not yet been tested.

On Thursday, the FDA for the first time accepted an application for a biosimilar under the BPCIA's new pathway. The drug in question is Zarzio, manufactured by the Novartis subsidiary Sandoz and already available in over 40 countries. Zarzio mimics Amgen's drug filgrastim (brand name Neupogen), a protein produced in E. coli that have been genetically modified to express the human gene for granulocyte colony-stimulating factor. It is used to restore immune function in patients undergoing chemotherapy or bone marrow transplants.

Even under the BPCIA, biosimilars face much steeper hurdles than generic small molecule drugs. For a protein biologic like filgrastim, Sandoz will have to provide evidence of the similarity of its product to Neupogen at every structural and functional level, from amino acid sequence to changes that occur within the cell after translation. More importantly, both animal and human trials may be required to demonstrate the safety and efficacy of the drug. However, the FDA does have the power to grant more leeway in these trials than it would for a novel drug, as it stated in a 2012 draft guidance on the BCPIA: "The scope and magnitude of clinical studies will depend on the extent of residual uncertainty about the biosimilarity of the two products after conducting structural and functional characterization and possible animal studies."

The acceptance of Sandoz' application for approval of "generic" filgrastim will offer the first opportunity to see how the FDA interprets these powers in practice. Previous biosimilars, like Sandoz' version of enoxaparin, have been approved under the earlier provisions for generics contained in the 1984 Hatch-Waxman Amendments; it is not yet clear whether the BPCIA pathway will provide enough of an advantage over this route to significantly affect the availability and pricing of biologics. The question is a pressing one, as a number of the best-selling biologics on the market, including Herceptin, Rituxan and Neulesta, are rapidly approaching patent expiration.