The US Food and Drug Administration (FDA) approved Roche's Cotellic (cobimetinib) for the treatment of people with BRAF V600E or V600K mutation-positive unresectable or metastatic melanoma in combination with Zelboraf (vemurafenib). Cotellic and Zelboraf are not used to treat melanoma with a normal BRAF gene.

Cotellic is Roche’s seventh new medicine approved by the FDA in the past five years.

“When used in combination, Cotellic and Zelboraf help delay disease progression and help people live significantly longer than with Zelboraf alone,” said Sandra Horning, M.D., chief medical officer and head of global product development.

“With this approval, people with this type of deadly and aggressive skin cancer now have a new targeted option.”

Today’s FDA approval is based on results from the phase III coBRIM study, which showed Cotellic plus Zelboraf reduced the risk of disease worsening or death (progression-free survival; PFS) by about half in people who received the combination [HR=0.56, 95 per cent CI (0.45-0.70); p<0.001], with a median PFS of 12.3 months for Cotellic plus Zelboraf compared to 7.2 months with Zelboraf alone. An interim analysis also showed the combination of Cotellic and Zelboraf helped people live significantly longer (overall survival; OS) than Zelboraf alone (HR=0.63, 95 per cent CI 0.47-0.85; p=0.0019). The objective response rate (tumour shrinkage) was higher with Cotellic plus Zelboraf compared to Zelboraf alone (70 vs. 50 per cent; p<0.001), as was the complete response rate (complete tumour shrinkage, 16 vs. 11 per cent).

Possible serious side effects with Cotellic include risk of skin cancers, increased risk of bleeding, heart problems that can lead to inadequate pumping of the blood by the heart, rash, eye problems, abnormal liver test or liver injury, increased levels of an enzyme in the blood, and photosensitivity. The most common side effects of Cotellic include diarrhea, sunburn or sun sensitivity, nausea, fever and vomiting. Cotellic can also cause changes in blood test results.

The final overall survival analysis from the coBRIM study will be presented at the Society for Melanoma Research 2015 International Congress (SMR) held in San Francisco, California from November 18-21.

In September, the Committee for Medicinal Products for Human Use (CHMP) at the European Medicines Agency (EMA) issued a positive opinion for Roche’s marketing authorisation application for Cotellic in the European Union. A decision from the European Commission is expected before the end of 2015. Cotellic was approved in Switzerland by Swissmedic in August 2015.

CoBRIM is an international, randomized, double-blind, placebo-controlled phase III study evaluating the safety and efficacy of 60 mg once daily of Cotellic plus 960 mg twice daily of Zelboraf compared to 960 mg twice daily of Zelboraf plus placebo. In the study, 495 patients with BRAF V600 mutation-positive unresectable locally advanced or metastatic melanoma (detected by the cobas 4800 BRAF Mutation Test) and previously untreated for advanced disease were randomized to receive Zelboraf every day on a 28-day cycle plus either Cotellic or placebo on days 1-21. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent. Investigator-assessed PFS is the primary endpoint. Secondary endpoints include PFS by independent review committee, objective response rate, overall survival, duration of response and other safety, pharmacokinetic and quality of life measures.

Melanoma is less common, but more aggressive and deadlier than other forms of skin cancer. BRAF is mutated in approximately half of melanomas. When melanoma is diagnosed early, it is generally a curable disease, but most people with advanced melanoma have a poor prognosis. More than 232,000 people worldwide are currently diagnosed with melanoma each year. In recent years, there have been significant advances in treatment for metastatic melanoma and people with the disease have more options. However, it continues to be a serious health issue with a high unmet need and a steadily increasing incidence over the past 30 years.