Exelixis (EXEL) received the first of the great news we expected to hear. Today, the U.S. Food and Drug Administration (FDA) approved COTELLIC™ (cobimetinib) a cancer drug discovered by Exelixis in combination with Roche’s drug vemurafenib for BRAF V600E or V600K mutation-positive unresectable or metastatic melanoma.
COTELLIC is a selective MEK inhibitor is subject of a worldwide collaboration agreement between Exelixis and Genentech (Roche). Switzerland had approved COTELLIC in August 2015 for the same condition.
Following the agreement with Exelixis, Genentech took charge of continuing Cotellic development and of sponsoring the U.S. New Drug Application (NDA).
We remind that Roche had filed for a Marketing Authorization Application (MAA) with the European Medicines Agency in late 2014, and the Committee for Medicinal Products for Human Use issued a positive opinion for the MAA in September 2015. Roche anticipates a decision from the European Commission by year-end.
“The approval of COTELLIC for use in combination with vemurafenib is an important milestone for the melanoma community, and also for Exelixis, as it is “the second medicine discovered in EXEL’s laboratories to receive regulatory approval in the United States,” said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis.
The COTELLIC approval is based on data from the phase 3 coBRIM study. The results of this study demonstrated COTELLIC plus vemurafenib reduced the risk of disease worsening or death (progression-free survival; PFS) by about half in people who received the combination. The results showed a median PFS of 12.3 months for COTELLIC plus vemurafenib compared to 7.2 months with vemurafenib alone.
An interim analysis also showed the combination of COTELLIC and vemurafenib increased overall survival (OS). People on the combination live significantly longer than those who took vemurafenib alone. The objective response rate (tumor shrinkage) was higher with COTELLIC plus vemurafenib compared to vemurafenib alone, as was the complete response rate (complete tumor shrinkage, 16 vs. 10 percent).
That’s why we expected approval of the drug.
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. (for detailed adverse effects please read the firm’s press release or visit the web that the developing firms will create for the drugs.)
The final overall survival analysis from the coBRIM trial will be presented at the Society for Melanoma Research 2015 International Congress, which will be held in San Francisco from November 18-21.
The agreement history: In November 2013, Exelixis exercised its option under the 2006 collaboration agreement to co-promote COTELLIC in the United States; accordingly, Exelixis will provide 25% of the sales force, closely coordinating its efforts with Genentech.
The Beef: 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. EXEL is also eligible to receive royalties on any sales of the product outside the country, including in Switzerland, where COTELLIC was first approved, and in the European Union, where Roche anticipates a regulatory decision by year-end.
Dr. Morrissey continued: “The approval of COTELLIC represents a major achievement for Exelixis and for all of the employees, past and present, who contributed to the program since its inception. As we enter the commercialization phase of our partnership with Genentech and Roche, our agreement enables Exelixis to participate meaningfully in the product’s introduction and ongoing sales, etc.,
About COTELLIC™ in Combination with Vemurafenib
COTELLIC™ (cobimetinib) is indicated for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, in combination with vemurafenib.
COTELLIC and vemurafenib are prescription medicines used in combination to treat melanoma that spread to other parts of the body or cannot be removed by surgery, and that has a certain type of abnormal BRAF gene.
Approximately half of melanomas have mutated BRAF, which causes abnormal signaling inside cancer cells leading to tumor growth. Vemurafenib 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 vemurafenib are thought to reduce cancer cell growth longer than with vemurafenib alone. A patient’s healthcare provider will perform a test to make sure COTELLIC and vemurafenib are right for the patient.
It is not known if COTELLIC and vemurafenib are safe and effective in children under 18 years of age.
Cabozantinib is an inhibitor of multiple tyrosine kinases, including MET, VEGFRs, AXL and RET that demonstrated encouraging clinical activity in earlier trials and is currently authorised for treatment of adult patients with progressive, unresectable locally-advanced, or metastatic medullary thyroid cancer.
Expression of MET or AXL could be associated with enhanced malignsant cell viability and aggressive tumor, which impact overall survival.
Cabozantinib was granted Breakthrough Therapy Designation by the US Food and Drug Administration (FDA) on 24 August 2015 for patients with renal cell carcinoma (RCC) who experienced disease progression following treatment with a tyrosine kinase inhibitor (TKI). This decision was based upon the results of the METEOR study.