Cotellic (cobimetinib) approved to be used in combination with vemurafenib for melanoma treatment

The U.S. Food and Drug Administration today approved Cotellic (cobimetinib) to be used in combination with vemurafenib to treat advanced melanoma that has spread to other parts of the body or can't be removed by surgery, and that has a certain type of abnormal gene (BRAF V600E or V600K mutation).

Melanoma is the most aggressive and dangerous form of skin cancer in the United States. It forms in the skin cells that develop the skin's pigment and if not diagnosed early, the cancer is likely to spread to other parts of the body. The National Cancer Institute estimates that 73,870 Americans will be diagnosed with melanoma and 9,940 will die from the disease this year.

"As we continue to advance our knowledge of tumor biology, we have learned that cancer cells have a remarkable ability to adapt and become resistant to targeted therapies. Combining two or more treatments addressing different cancer-causing targets may help to address this challenge," said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research. "Today's approval provides a new targeted treatment that, when added to vemurafenib, demonstrates greater benefit than vemurafenib alone in patients with BRAF mutation-positive melanoma."

Cotellic works by blocking the activity of an enzyme known as MEK, which is part of a larger signaling pathway. Abnormal activity of signaling pathways can lead to cancer. Cotellic prevents or slows cancer cell growth. Vemurafenib, marketed in the U.S. as Zelboraf, is a BRAF inhibitor that affects a different part of the same pathway and was approved in 2011 to treat patients with melanoma that has spread to other parts of the body or cannot be removed by surgery, whose tumors express a gene mutation called BRAF V600E, as detected by an FDA approved test. Health care providers should confirm the presence of BRAF V600 E or V600K mutation in their patients' tumor specimens using one of the available FDA approved tests prior to starting treatment with Cotellic in combination with vemurafenib.

The safety and efficacy of Cotellic taken in combination with vemurafenib were demonstrated in a randomized clinical study of 495 patients with previously untreated, BRAF V600 mutation-positive melanoma that is advanced or cannot be removed by surgery. All study participants received vemurafenib and were then randomly selected to also take either Cotellic or a placebo. On average, patients taking Cotellic plus vemurafenib experienced a delay in the amount of time it took for their disease to worsen (approximately 12.3 months after starting treatment) compared to approximately 7.2 months after starting treatment for those taking vemurafenib only. In addition, patients taking Cotellic plus vemurafenib lived longer, with approximately 65 percent of patients alive 17 months after starting treatment as compared to half of those taking vemurafenib only. Additionally, 70 percent of those taking Cotellic plus vemurafenib experienced complete or partial shrinkage of their tumors, compared to 50 percent among those taking vemurafenib plus placebo.

The most common side effects of treatment with Cotellic in combination with vemurafenib are diarrhea, sensitivity to ultraviolet (UV) light (photosensitivity reaction), nausea, fever (pyrexia) and vomiting.

Cotellic may cause severe side effects including damage to the heart muscle (cardiomyopathy) or to other muscles (rhabdomyolysis), new skin tumors (primary cutaneous malignancies), eye disease (retinal detachment), severe skin rash, liver damage (hepatotoxicity), hemorrhage and severe skin rash due to increased sensitivity to sunlight (photosensitivity). People taking Cotellic should avoid sun exposure, wear protective clothing, and a broad spectrum ultraviolet A/ultraviolet B sunscreen to protect against sunburn. Women taking Cotellic should use effective contraception, as the medication can cause harm to a developing fetus.

Cotellic was reviewed under the FDA's priority review program that provides for an expedited six-month review of drugs that, at the time the application was submitted, have the potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition. Cotellic also received orphan drug designation, which provides incentives such as tax credits, user fee waivers and eligibility for orphan drug exclusivity to assist and encourage the development of drugs for rare diseases.

Cotellic and Zelboraf are both marketed by Genentech of San Francisco, California.