FDA Approves Nivolumab for Patients with Advanced, Refractory Melanoma

Intended for patients previously treated with ipilimumab and for BRAF 600 mutation-positive melanoma after treatment with ipilimumab and a BRAF inhibitor

On 22 December, 2014 the USA Food and Drug Administration (FDA) granted accelerated approval to nivolumab (Opdivo), a new treatment for patients with unresectable or metastatic melanoma who no longer respond to other drugs.

Immunotherapeutic, nivolumab is a PD-1 inhibitor. It is intended for patients who have been previously treated with ipilimumab and, for melanoma patients whose tumours express a BRAF V600 mutation, for use after treatment with ipilimumab and a BRAF inhibitor.

“Opdivo is the seventh new melanoma drug approved by the FDA since 2011,” said Dr Richard Pazdur, 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.”
Other FDA-approved treatments for melanoma include ipilimumab (2011), peginterferon alfa-2b (2011), vemurafenib (2011), dabrafenib (2013), trametinib (2013) and pembrolizumab (2014).

Nivolumab is being approved more than three months ahead of the prescription drug user fee goal date of 30 March, 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 is being approved under the FDA’s accelerated approval programme, 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 programme provides earlier patient access to promising new drugs while the company conducts additional clinical trials to confirm the drug’s benefit.

Nivolumab’s efficacy was demonstrated in 120 clinical trial participants with unresectable or metastatic melanoma. Results showed that 32% of participants receiving nivolumab had objective response rate. This effect lasted for more than six months in approximately one-third of the participants who experienced tumour shrinkage.

Nivolumab’s 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 oedema. The most serious side effects are severe immune-mediated side effects involving healthy organs, including the lung, colon, liver, kidneys and hormone-producing glands.

Opdivo is marketed by Princeton, New Jersey-based Bristol-Myers Squibb.