FDA Rubber-Stamps Bristol-Myers Squibb’s Melanoma mAb

BMS reports this is the first new treatment for unresectable metastatic melanoma in over a decade.

FDA approved Bristol-Myers Squibb’s (BMS) monoclonal antibody Yervoy™ (ipilimumab) 3 mg/kg for the treatment of unresectable or metastatic melanoma. The firm claims Yervoy is the only approved therapy for unresectable or metastatic melanoma that has demonstrated a significant improvement in overall survival. It is also the first treatment sanctioned for this indication in over a decade, according to the Melanoma Research Foundation (MRF). Interleukin-2, the last drug to have been approved for treating melanoma, only benefits 10-15% of patients with advanced disease, the organization points out. Yervoy is a recombinant human monoclonal antibody that blocks the CTLA-4 T lymphocyte antigen.

Yervoy was filed with the European regulatory authorities in April 2010, where the review process is ongoing. Approval of the drug in the U.S. was based on a Phase III study involving 676 patients with unresectable or metastatic melanoma who had previously been treated with aldesleukin, dacarbazine, temozolomide, fotemustine, carboplatin, or a combination of these drugs. The results showed that median overall survival was 10 months for patients treated using Yervoy, compared with six months for treatment using gp100. Combined therapy using Yervoy and gp100 also resulted in a median overall survival of 10 months.  

Kaplan-Meier estimates suggested the overall survival rates at one year were 46% for Yervoy-treated patients, compared with 25% for patients in the gp100 arm. Estimated survival at two years was 24% for the Yervoy arm, versus 14% for the gp100 arm. Yervoy-treated patients also demonstrated a 32% reduction in the risk of death compared with gp100 control patients.

“FDA approval of Yervoy is the culmination of more than 14 years’ of research and development,” remarks Elliott Sigal, M.D., executive vp, CSO, and president of R&D at BMS. “Yervoy is the first FDA-approved compound from our robust immuno-oncology pipeline, which comprises a variety of other compounds with the potential to harness the patient’s immune system to fight cancer.”

“This is a critical breakthrough for advanced-stage melanoma patients who have far too few approved treatment options available,” adds Timothy J. Turnham, executive director of MRF. “Patients have been waiting for a life-changing innovation like this one and news of the approval has galvanized the patient community.”

Treatment using Yervoy has been associated with severe and potentially fatal immune-mediated adverse-reactions due to T-cell activation and proliferation. The drug will be accompanied with a Risk Evaluation and Mitigation Strategy to inform prescribers of the potential adverse effects.  BMS has, meanwhile, separately been working with FDA to design post-marketing study that will evalaute the safety and efficacy of a 10 mg/kg dose of Yervoy, compared with the approved 3 mg/kg dose, in patients with unresectable or metastatic melanoma.