Roche, GSK Advance Separate Combination Therapies for Melanoma

In positioning themselves in the anticancer market, Roche and GlaxoSmithKline separately reported positive results from Phase III studies for combination therapies that they are developing to treat melanoma. The combination products respectively pair the companies’ MEK inhibitors with other anticancer drugs developed by the companies.

Roche reported positive Phase III results for a combination therapy of its anticancer drug Zelboraf (vemurafenib) and cobemetinib, a MEK inhibitor discovered by the biopharmaceutical company Exelixis Inc and which is being developed with Roche. Roche plans to submit these data to the US Food and Drug Administration (FDA), European Medicines Agency, and other health authorities for potential approval.

The Phase III study demonstrated that cobimetinib, used in combination with Zelboraf, helped patients with previously untreated BRAF V600 mutation-positive advanced melanoma live longer without their disease worsening (progression-free survival; PFS) compared to Zelboraf alone.

Zelboraf was approved by the FDA in 2011 to treat late-stage or unresectable melanoma for patients whose tumors express a gene mutation called BRAF V600E. Cobimetinib is designed to selectively block the activity of MEK, one of a series of proteins inside cells that make up a signaling pathway that helps regulate cell division and survival. Cobimetinib binds to MEK while Zelboraf binds to mutant BRAF, another protein on the pathway, to interrupt abnormal signaling that can cause tumors to grow. In addition to the combination with Zelboraf in melanoma, cobimetinib is also being investigated in combination with several investigational medicines, including an immunotherapy, in several tumor 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 Roche’s 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 end of Phase I development, 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 commercialization costs. Exelixis is eligible to receive royalties on any sales of the product outside the United States.

In another development GSK reported that the Independent Data Monitoring Committee (IDMC) recommended that a Phase III study comparing its MEK inhibitor Mekinist (trametinib), in combination with its BRAF inhibitor, Tafinlar (dabrafenib), to vemurafenib in patients with BRAF V600E or V600K mutation-positive unresectable or metastatic cutaneous melanoma be stopped early based on an interim analysis that showed an overall survival benefit for the trametinib and dabrafenib combination compared to vemurafenib that crossed the pre-specified efficacy stopping boundary. The safety profile of the trametinib and dabrafenib arm was consistent with the safety profile of the combination observed to date.

The IDMC recommendation is based on headline data; further analysis of safety and efficacy data is underway and will be completed in the coming months.

Source: Roche and GlaxoSmithKline


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