FDA Grants Accelerated Approval to Nivolumab for Unresectable and Metastatic Melanoma

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Marketed by Bristol-Myers Squibb as Opdivo, this PD-1 inhibitor was previously granted breakthrough status.

The FDA today granted accelerated approval to nivolumab, a new treatment for patients with unresectable or metastatic melanoma who no longer respond to other drugs.

Nivolumab, marketed by Bristol Myers-Squibb as Opdivo, had previously been granted breakthrough status by the FDA. The therapy works by inhibiting the PD-1 protein on cells, which blocks the body’s immune system from attacking melanoma tumors. Nivolumab is intended for patients who have been previously treated with ipilimumab and, for melanoma patients whose tumors express a gene mutation called BRAF V600, for use after treatment with ipilimumab and a BRAF inhibitor.

The drug is the seventh new melanoma drug approved by the FDA since 2011, according to Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “The continued development and approval of novel therapies based on our increasing understanding of tumor immunology and molecular pathways are changing the treatment paradigm for serious and life-threatening diseases,” Dr Pazdur said.


Other FDA-approved treatments for melanoma include ipilimumab (2011), peginterferon alfa-2b (2011), vemurafenib (2011), dabrafenib (2013), trametinib (2013) and pembrolizumab (2014). Opdivo is being approved more than three months ahead of the prescription drug user fee goal date of March 30, 2015, the date when the agency was scheduled to complete its review of the application.

The FDA granted nivolumab breakthrough therapy designation, priority review and orphan product designation because the sponsor demonstrated through preliminary clinical evidence that the drug may offer a substantial improvement over available therapies; the drug had the potential, at the time of the application was submitted, to be a significant improvement in safety or effectiveness in the treatment of a serious condition; and the drug is intended to treat a rare disease, respectively.

Nivolumab being approved under the FDA’s accelerated approval program, which allows approval of a drug to treat a serious or life-threatening disease based on clinical data showing the drug has an effect on a surrogate endpoint reasonably likely to predict clinical benefit to patients. This program provides earlier patient access to promising new drugs while the company conducts additional clinical trials to confirm the drug’s benefit.

Its efficacy was demonstrated in 120 clinical trial participants with unresectable or metastatic melanoma. Results showed that 32% of participants receiving nivolumab had their tumors shrink. This effect lasted for more than 6 months in approximately one-third of the participants who experienced tumor shrinkage.

Safety was evaluated in the overall trial population of 268 participants treated with nivolumab and 102 participants treated with chemotherapy. The most common side effects of the drug were rash, itching, cough, upper respiratory tract infections, and fluid retention (edema). The most serious side effects are severe immune-mediated side effects involving healthy organs, including the lung, colon, liver, kidneys and hormone-producing glands.