By Edward Li, PharmD, BCOP, Drugs and Biologics Editor
Most clinicians are familiar with using generic drugs as part of their daily practice. With relatively few exceptions, generics are considered to be equivalent to their branded counterparts in terms of bioequivalence, safety, and efficacy, yet may be considerably less expensive. However, the equivalence of generic drugs has been recently questioned, and another concept is emerging that can further complicate the role of generics in medicine: the approval of biosimilar agents1.
Biosimilars have become a center of discussion following the enactment of the Biologics Price Competition and Innovation Act of 2009 (BPCI Act), which "establishes an abbreviated approval pathway for biological products that are demonstrated to be 'highly similar' (biosimilar) to, or 'interchangeable' with, an FDA-licensed biological product."2 Thus, a "biosimilar" can be loosely defined as a "generic" version of a therapeutic biologic (i.e., it is not made by the innovator company) and is approved under an abbreviated process. Examples of biologics used in the oncology setting include (but are not limited to) monoclonal antibodies, cytokines, erythropoiesis stimulating agents, and myeloid growth factors.
Biosimilars have come to the forefront of discussion because of their potential to reduce health care costs. However, there are significant scientific and manufacturing challenges to ensuring that a biosimilar is "highly similar" to the innovator product. The BPCI Act requires that the FDA develop a robust biosimilar approval pathway, but this raises questions regarding what types of studies (pre-clinical and clinical) would be required to gain FDA approval. Furthermore, biosimilars exude safety concerns related to immunogenicity, and these adverse effects must be tracked. Potentially, clinicians may be hesitant to utilize biosimilars, and a low uptake of these agents (coupled with a heavy investment in biosimilar development) may minimize the cost-benefit derived from a lower acquisition price of biosimilars.
The FDA convened a stakeholder meeting on November 2-3, 2010 to discuss and address some of these concerns when developing the biosimilar approval pathway. In attendance were representatives from various groups such as providers, patient advocacy, and industry. Key concepts discussed at this meeting revolved around clinical trial design (e.g., what types of studies are necessary, how these are studies designed, etc.), pharmacovigilance efforts, and interchangeability in the clinical setting.
Regardless of the approval pathway decided upon by the FDA, it is ultimately up to oncologists and other practitioners to determine whether a particular biosimilar agent is interchangeable and will be utilized in day-to-day practice. For example, clinicians will need to perform their own critical review of the evidence and utilize their judgment to determine if the use of a biosimilar agent can be extrapolated into other indications beyond those deemed to be interchangeable by the FDA. Additionally, one can expect third-party payors to perform their own analysis and develop interchangeability coverage policies.
To discuss some of these issues noted above, NCCN plans to convene an Oncology Policy Summit on Biosimilars in 2011. As with other NCCN Oncology Policy Summits, this will be a forum for key policy organizations, thought leaders, and other stakeholders to participate in discussions about how these new regulations will impact oncology care.
1Alderman L. Not All Drugs Are the Same After All. The New York Times. December 18, 2009. http://www.nytimes.com/2009/12/19/health/19patient.html. Accessed November 22, 2010.
2 Federal Register, Volume 75, No. 192, Tuesday, October 5, 2010, page 61497.