Genentech, a member of the Roche Group and Exelixis’ ollaborator, has completed the filing of its New Drug Application (NDA) with the US Food and Drug Administration (FDA) for cobimetinib, a specific MEK inhibitor discovered by Exelixis, in combination with vemurafenib for previously untreated patients with unresectable locally advanced or metastatic melanoma harboring a BRAF V600 mutation.
Cobimetinib has received Fast Track designation by the FDA. Roche submitted a Marketing Authorisation Application for the combination to the European Medicines Agency in September of this year.
The NDA is based on data from the coBRIM trial, a phase 3 pivotal trial conducted by Genentech in 495 patients with BRAF V600 mutation-positive unresectable locally advanced or metastatic melanoma. As presented during the Presidential Symposium at the European Society for Medical Oncology 2014 Congress, coBRIM met its primary endpoint, demonstrating a statistically significant increase in investigator-determined progression-free survival (PFS). The median PFS was 9.9 months for the combination of cobimetinib and vemurafenib versus 6.2 months for vemurafenib alone (hazard ratio [HR] = 0.51, 95 percent CI 0.39-0.68; p < 0.0001). The safety profile of the combination was consistent with that observed in a previous study of the combination. The most common Grade 3 or higher adverse events in the combination arm included liver lab abnormalities, elevated creatine phosphokinase and diarrhea. The most common adverse events seen in the combination arm included diarrhea, nausea, rash, photosensitivity and lab abnormalities.
Exelixis discovered cobimetinib internally and advanced the compound to investigational new drug (IND) status. In late 2006, Exelixis entered into a worldwide co-development agreement with Genentech, under which Exelixis received initial upfront and milestone payments in connection with signing the agreement and submitting the IND. Exelixis was responsible for development of cobimetinib through the determination of the maximum tolerated dose in phase 1, at which point Genentech exercised its option to further develop the compound.
In November 2013, Exelixis exercised its option to co-promote cobimetinib, if approved, in the United States. Exelixis is entitled to an initial equal share of US profits and losses, which will decrease as sales increase, and will share equally in the US marketing and commercialisation costs. Exelixis is eligible to receive royalties on any sales of the product outside the United States.