Robert Rifkin, MD, FACP
As expensive cancer biologics move off patent, biosimilar products are coming on board. These are highly similar versions of licensed biologics that demonstrate near-fingerprint identity to their reference products in terms of structure and potency. Biosimilars represent a major opportunity for cost savings and will in turn serve to increase patient access to effective drugs.
Biosimilars entered the European Union’s marketplace in 2006 with the approval by the European Medicines Agency (EMA) of Omnitrope (somatropin). The EMA established the term “biosimilar” in recognition that the products are similar to the originator, using essentially the same active ingredient of the reference product. As stated by the European Commission, “no two cell lines, developed independently, can be considered identical. This is why biotechnology-derived medicines cannot be fully copied.”1 In recognition of this, the EMA established the term “biosimilar.” For biosimilars, the structure, functions, pharmacokinetic profiles, pharmacodynamic effects, and efficacy must be shown comparable to the reference product. The biosimilar also must show it has no clinically meaningful differences in terms of safety from the reference product.
To date, the EMA has approved 22 biosimilar agents within the product classes of human growth hormone, granulocyte colony-stimulating factor, erythropoiesis-stimulating agent, insulin, follicle-stimulating hormone, and tumor necrosis factor-α inhibitors; two biosimilar approvals have been withdrawn, leaving a total of 20 biosimilars currently being prescribed in Europe.
Biosimilars in the United States
These novel compounds have since been slowly making their way into the U.S. marketplace. In March 2015, the U.S. Food and Drug Administration (FDA) approved the first biosimilar product, filgrastim-sndz (Zarxio). Since then, three other biosimilars have been approved: infliximab-dyyb (Inflectra), etanercept-szzs (Erelzi), and most recently, adalumumab-atto (Amjevita), which received FDA approval for the treatment of multiple inflammatory diseases on September 23, 2016.
Oncologists have filgrastim-sndz as an alternative to the reference product filgrastim (Neupogen), the granulocyte colony-stimulating factor analog that was first licensed for use in 1991. In patients with nonmyeloid malignancies who are receiving myelosuppressive chemotherapy, filgrastim is indicated to decrease the incidence and duration of neutropenia and febrile neutropenia following chemotherapy. Filgrastim-sndz is listed within the National Comprehensive Cancer Network® (NCCN®) Guidelines for Myeloid Growth Factors and appears in many drug formularies. Biosimilar versions of many other oncology agents are expected to become available in the next few years as originator molecule patents expire.
Phase III trials are completed or underway of biosimilar forms of several antitumor drugs, including biosimilar trastuzumab in HER2-positive early breast cancer and metastatic breast cancer [reference product, trastuzumab (Herceptin)]; biosimilar rituximab in follicular lymphoma, indolent non-Hodgkin lymphoma, and diffuse large B-cell lymphoma [reference product, rituximab (Rituxan)]; biosimilar bevacizumab in non–small cell lung cancer and colorectal cancer [reference product, bevacizumab [Avastin]; and biosimilar cetuximab (Erbitux) in head and neck cancer [reference product, cetuximab (Erbitux)].
More growth factors should also soon join filgrastim-sndz, including biosimilar products for pegfilgrastim (Neulasta) and epoetin alfa (Epogen, Procrit). Oncologists will then be given the choice of several biosimilars as alternatives to current reference agents.
It is important, therefore, for oncologists to understand the nuances of these interesting new agents, and to know how to discuss them with patients. What will they mean to your practice? Our roundtable faculty debated a number of issues relevant to their emerging use. We hope our readers will find this information useful in their own practices.■
—Robert Rifkin, MD, FACP
Guest Editor
Reference
1. European Commission: What you need to know about biosimilar products. Process on corporate responsibility in the field of pharmaceuticals. A consensus information document, 2013. Available at http://www.sandozbiosimilars.com/cs/groups/public/@sbs_com/documents/document/n_prod_625239.pdf. Accessed September 1, 2016.
