The FDA has accepted for priority review a biologics license application for avelumab (EMD Serono/Pfizer) as a proposed treatment for patients with metastatic Merkel cell carcinoma (MCC). Avelumab is an investigational, fully human anti-programmed death ligand-1 (PD-L1) immunoglobulin G1 monoclonal antibody. If approved, it would be the first treatment indicated for metastatic MCC in the United States.
By inhibiting PD-L1 interactions, avelumab is thought to enable the activation of T cells and the adaptive immune system. By retaining a native Fc-region, avelumab is thought to potentially engage the innate immune system and induce antibody-dependent cell-mediated cytotoxicity.
The FDA submission was supported by positive data from the JAVELIN Merkel 200 trial, a multicenter, single-arm, open-label, phase 2 study involving 88 patients with metastatic MCC whose disease had progressed after at least one chemotherapy treatment. Avelumab was administered intravenously at a dose of 10 mg/kg every two weeks. The study’s primary endpoint was a confirmed objective response (a complete response or a partial response). The patients were followed for a median period of 10.4 months. An objective response was achieved in 28 patients (32%), including eight complete responses and 20 partial responses. The results from this study were published in Lancet Oncology in October 2016.
The FDA’s priority review designation reduces the review time from 10 months to a goal of six months from the day of filing and is given to drugs that may offer major advances in treatment or may provide a treatment where no adequate therapy exists. The FDA previously granted avelumab an orphan drug designation for MCC, as well as fast track and breakthrough therapy designations for the treatment of patients with metastatic MCC whose disease had progressed after at least one previous chemotherapy regimen. Breakthrough therapy status is intended to expedite the development and review of treatments for serious or life-threatening diseases where preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies for one or more endpoints.
In November 2014, Merck KGaA, Darmstadt, Germany, and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab. EMD Serono is Merck’s biopharmaceutical business arm.