Exelixis, Genentech's Cobimetinib Succeeds in Pivotal Phase III Trial
October 6, 2015
By Alex Keown, BioSpace.com Breaking News Staff
SOUTH SAN FRANCISCO, Calif. – Genentech and its partner Exelixis, Inc. are rapidly moving closer to regulatory approval of its cancer drug cobimetinib after both companies announced positive results from a late stage study.
Cobimetinib is a specific MEK inhibitor discovered by Exelixis, in combination with vemurafenib in previously untreated patients with unresectable locally advanced or metastatic melanoma carrying a BRAF V600 mutation. The latest Phase III trial met its endpoint of demonstrating a statistically significant and clinically meaningful increase in overall survival for patients receiving the combination of cobimetinib and vemurafenib (marketed by Genentech as Zelboraf), Exelixis said in a statement. Long term safety data is expected later this year. Cabozantinib is currently marketed in capsule form under the brand name Cometriq in the United States for the treatment of progressive, metastatic medullary thyroid cancer. It is also approved in the European Union for the treatment of adult patients with progressive, unresectable locally advanced or metastatic MTC.
“The positive effect of the combination of cobimetinib and vemurafenib on overall survival is a major step forward for patients with advanced BRAF V600 mutation-positive melanoma in search of new treatment options,” Michael M. Morrissey, president and chief executive officer of Exelixis, said in a statement.
Cobimetinib is a selective inhibitor that blocks the activity of MEK, a protein kinase that is part of a key pathway that promotes cell division and survival. This pathway is frequently activated in human cancers including melanoma, where mutation of one of its components (BRAF) causes abnormal activation in about 50 percent of tumors, Exelixis said. Approximately 50 percent of patients with the BRAF mutation experience a “tumor response” when treated with a BRAF inhibitor.
In July, Exelixis announced top-line results from METEOR, its phase 3 pivotal trial comparing cabozantinib to everolimus in 658 patients with metastatic renal cell carcinoma, a type of kidney cancer, who have experienced disease progression following treatment with a VEGF receptor tyrosine kinase inhibitor. In August, the U.S. Food and Drug Administration (FDA) granted Cabozantinib breakthrough therapy designation for RCC.
Cobimetinib, the Exelixis-discovered selective inhibitor of MEK, was approved in Switzerland in August for use in combination with vemurafenib as a treatment for patients with advanced melanoma. The FDA is expected to rule on the drug on Nov. 11. If cobimetinib is approved in the United States, Exelixis is entitled to an initial equal share of U.S. profits and losses, which will decrease as sales increase, and will share in U.S. marketing and commercialization costs.
Some analysts have predicted sales of the combination drug to be approximately $800 million annually. Having exercised its option to co-promote the compound in the United States, Exelixis is prepared to field up to 25 percent of the U.S. sales force, the company said.
Exelixis shares rights with Genentech for cobimetinib. The two companies inked a deal to co-develop the drug in 2006. Under terms of that deal Exelixis received initial upfront and milestone payments for signing the agreement and submitting the Investigational New Drug application.
Exelixis is hoping the approval of the two drugs will turn around the company’s fortunes after it was forced to lay off 70 percent of its workforce after a 2014 trial for cabozantinib failed to meet its goal of extending the lives of prostate cancer patients. The trial’s failure and the layoffs caused the stock to drastically fall. Exelixis’ is slightly down this morning trading at $5.90 per share.
In September, Bay Area-based Exelixis hired three new executives to guide the company through commercialization and an expansion of its medical affairs in anticipation of the approval of cobimetinib and cabozantini.