Exelixis, announced that cobimetinib, an Exelixis-discovered compound, will be the subject of a clinical data presentation at the European Society for Medical Oncology (ESMO) 2014 Congress. During the meeting, which will be held from September 26-30, 2014, in Madrid, Spain, investigators will present initial data from coBRIM, the ongoing phase 3 pivotal trial of cobimetinib in combination with vemurafenib in patients with previously untreated BRAF V600 mutation-positive advanced melanoma.
On July 13, 2014, Exelixis announced positive top-line results from coBRIM after being informed by Genentech, a member of the Roche Group and Exelixis’ collaborator, that coBRIM met its primary endpoint, delivering a statistically significant increase in progression-free survival (PFS) for the combination of cobimetinib plus vemurafenib as compared to vemurafenib alone. Roche has indicated that it will initiate regulatory filings for the combination of cobimetinib and vemurafenib before the end of the year.
Cobimetinib is a selective inhibitor that blocks the activity of MEK, a protein kinase that is part of a key pathway (the RAS-RAF-MEK-ERK 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 per cent of Tumours. Tumours with BRAF mutations may develop resistance and subsequently progress after treatment with a BRAF inhibitor. In preclinical melanoma models, co-treatment with vemurafenib and the MEK inhibitor cobimetinib can delay the emergence of resistant Tumours. In addition to the combination with vemurafenib in melanoma, cobimetinib is also being investigated in combination with several investigational medicines, including an immunotherapy, in several Tumour types, including non-small cell lung cancer and colorectal cancer.
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 for 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.