“The FDA Granted Priority Review, Assigns Action Date of August 11, 2015” This is a subtitle in the firm’s news today, which says a lot about Exelixis (EXEL) as an active biotech firm.
Exelixis has, indeed, designed, produced and developed a rich pipeline of small molecule cancer targeted products. The firm might have experienced a setback in one of its drugs in an indication other than this drug has been approved for. The result was a selloff that ate the firm’s scientific value, the values of its pipeline products, patented technologies and drugs and of the alliances who rushed to sublicense, develop and market exelixis licensed drugs.
In today’s news, the FDA has accepted for review Genentech’s (Exelixis partner on the drug) New Drug Application (NDA) for cobimetinib in combination with vemurafenib for patients with unresectable or metastatic melanoma harboring a BRAF V600 mutation.
Cobimetinib is a specific MEK inhibitor. It was discovered by Exelixis and is now the subject of a worldwide co-development agreement between Exelixis and Genentech, a member of the Roche Group.
The FDA Granted Priority Review to the NDA and assigned a Prescription Drug User Fee Act (PDUFA) action date of August 11, 2015. This means that the FDA determined that the combination treatment has the potential to provide significant improvements in the treatment, of advanced melanoma with positive BRAF V600 mutation. This form of melanoma needs new approaches for a more effective treatments.
The NDA is based on data from coBRIM, a phase 3 pivotal trial conducted by Genentech. Roche also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency for the combination of cobimetinib and vemurafenib in 2014.
To learn about the coBRIM Study in the firm’s press release Click HERE
Results: Regarding the results of this trial as presented during the Presidential Symposium at the European Society for Medical Oncology 2014 Congress, coBRIM met its primary endpoint, demonstrating 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 laboratory abnormalities, elevated creatine phosphokinase and diarrhea. The most common adverse events seen in the combination arm included diarrhea, nausea, rash, photosensitivity and laboratory value abnormalities.
The Exelixis/Genentech Collaboration
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 U.S. profits and losses, which will decrease as sales increase, and will share equally in the U.S. marketing and commercialization costs. Exelixis is eligible to receive royalties on any sales of the product outside the United States.
Cobimetinib/ Vemurafenib Combination
Cobimetinib: 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% of tumors. Tumors with BRAF mutations may develop resistance and subsequently progress after treatment with a BRAF inhibitor.
Vemurafenib: marketed as Zelboraf, the drug is a B-Raf enzyme inhibitor developed by Plexxicon, which has become part of Daiichi-Sankyo) and Genentech. The drug is indicated for the treatment of late-stage melanoma.
In preclinical melanoma models, co-treatment with vemurafenib and the MEK inhibitor cobimetinib may delay the emergence of resistant tumors.
We believe this news is excellent, marking the beginning of Excelixis pipeline products march with faster steps towards approval and marketing of further products. The approval of the combination will also open the door for Exelixis to design and develop improved targeted drugs for cancers, as knowledge is improving about cancer pathways, cancer mutations and tumors’ resistance to treatments.
For Other Cancers Too: It is important to note that cobimetinib is also being tested in combination with several investigational medicines, including an immunotherapy in several tumor types, including non-small cell lung cancer, colorectal cancer, triple-negative breast cancer and melanoma.
We love the news and the agreement about sharing every aspect of the drug’s marketing in the U.S. and about the royalties in other countries
With all what happened against this firm and the interest of its shareholders, we did not remove Exelixis from our portfolio of picked biotech stocks since we picked it.