South San Francisco, Calif. – Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced Nov. 10 that the U.S. Food and Drug Administration (FDA) approved 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 Genentech’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.”

The 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 percent 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) than Zelboraf alone (HR=0.63, 95 percent CI 0.47-0.85; p=0.0019). The objective response rate (tumor shrinkage) was higher with Cotellic plus Zelboraf compared to Zelboraf alone (70 vs. 50 percent; p<0.001), as was the complete response rate (complete tumor shrinkage, 16 vs. 10 percent). 

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 (SMR) 2015 International Congress 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 authorization 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. 

Cotellic will be available to people in the United States within two weeks. For those who qualify, Genentech plans to offer patient assistance programs for people taking Cotellic in combination with Zelboraf through Genentech Access Solutions. Doctors can contact Genentech Access Solutions at (888) 249-4918. More information is also available athttp://www.Genentech-Access.com.

About the coBRIM study 

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. 

About Cotellic plus Zelboraf

Cotellic and Zelboraf are prescription medicines used in combination to treat melanoma that has spread to other parts of the body or cannot be removed by surgery, and that has a certain type of abnormal “BRAF” gene. Found in approximately half of melanomas, mutated BRAF causes abnormal signaling inside cancer cells leading to tumor growth. Zelboraf is designed to inhibit some mutated forms of BRAF and Cotellic is designed to inhibit some forms of MEK. Both BRAF and MEK are proteins in a cell signaling pathway that help control cell growth and survival. When used in combination, Cotellic and Zelboraf are thought to reduce cancer cell growth longer than with Zelboraf alone. A patient’s healthcare provider will perform a test to make sure Cotellic and Zelboraf are right for the patient. It is not known if Cotellic and Zelboraf are safe and effective in children under 18 years of age. 

About advanced melanoma 

Melanoma is less common, but more aggressive and deadlier than other forms of skin cancer. When melanoma is diagnosed early, it is generally a curable disease, but most people with advanced melanoma have a poor prognosis. The American Cancer Society estimates there will be nearly 74,000 new cases of melanoma and 10,000 melanoma deaths this year in the United States. 

In recent years, there have been significant advances in treatment for advanced 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.

About Cotellic 

Cotellic is a prescription medicine used with Zelboraf for the treatment of patients with a type of skin cancer called melanoma that has spread to other parts of the body or cannot be removed by surgery, and has a certain type of abnormal BRAF gene. Cotellic is not used to treat melanoma with a normal BRAF gene. Cotellic was discovered by Exelixis Inc. and was developed by Genentech in collaboration with Exelixis. Cotellic is also being investigated in combination with several investigational medicines, including an immunotherapy, in several tumor types such as non-small cell lung cancer and colorectal cancer.

About Zelboraf

Zelboraf was the first prescription treatment for patients with a type of skin cancer called melanoma that has spread to other parts of the body or cannot be removed by surgery, and has a certain type of abnormal BRAF gene as detected by an FDA-approved test. Cotellic and Zelboraf are not used to treat melanoma with a normal BRAF gene. Zelboraf is now approved in more than 90 countries and has been used to treat more than 20,000 patients worldwide. Zelboraf was co-developed under a 2006 license and collaboration agreement between Roche and Plexxikon, now a member of the Daiichi Sankyo Group.