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By Robert G. Bell

Robert BellThe Oncolotics Drug Advisory Committee (ODAC) of the Food and Drug Administration (FDA) has recommended approval of a biosimilar version of filgrastim. The product (EP2006 / Zarzio) by Sandoz will be deemed the first U.S. biosimilar based on Amgen’s Neupogen and the first one approved using the 351(k) approval pathway. Filgrastim is a granulocyte colony stimulating factor (G-CSF) used to treat neutropenia associated with cancer treatments. Based on ODAC review, the analytical data for Sandoz’s EP2006 demonstrates that its clinical product lots are highly similar to the reference product (Neupogen) notwithstanding minor differences in clinically inactive components. The proposed commercial EP2006 drug product (Zarzio) is also analytically highly similar to U.S.-licensed Neupogen with the exception of protein content, which was slightly lower than that of U.S.-licensed Neupogen. (The lower protein content of the proposed commercial Zarzio appears to be manufacturing related and may be resolved by manufacturing and control strategies.)

The clinical development results suggest that Sandoz’s data meets the requirement for a demonstration of “no clinically meaningful differences” between the proposed product and the reference product in terms of safety, purity, and potency. The results from the comparative pharmacokinetic (PK) and pharmacodynamic (PD) studies in normal human healthy subjects (i.e., PK and PD similarity studies), which were extensive and robust both in terms of the number of the studies and the number of different doses of EP2006, EU-approved Neupogen, and U.S.-licensed Neupogen, adequately supported that there are no clinically meaningful differences between EP2006 and U.S.-licensed Neupogen. This was further supported by a comparative clinical study (EP06-302), which enrolled patients with breast cancer receiving taxotere, adriamycin, and cyclophosphamide chemotherapy, who were randomized to receive either EP2006 or U.S.-licensed Neupogen. ODAC’s review of the efficacy and safety results of EP06-302 focused on Cycle 1, and these data provided additional support that there are no clinically meaningful differences between EP2006 and U.S.-licensed Neupogen.

Although FDA usually accepts the recommendations from ODAC, it is not required to agree with or accept them. A decision is expected in the coming months. This is great news for the U.S. health care system and patients. It’s been a long time coming. It’s also interesting to note that in Europe, Sandoz’s Zarzio (filgrastim) has become the first biosimilar to overtake both its reference product (Neupogen) and European market leader (Chugai’s Granocyte) and is now the most prescribed daily G-CSF in Europe and the number one biosimilar daily G-CSF globally.

Never say never.

Robert G. Bell, Ph.D., is president and owner of Drug and Biotechnology Development LLC, a consultancy to the pharmaceutical industry and academia for biological, drug, and device development.