EU CHMP recommends approval of Tafinlar + Mekinist (dabrafenib + trametinib) in metastatic melanoma with BRAF V600- Novartis

Novartis announced that the Committee for Medicinal Products for Human Use of the European Medicines Agency has adopted a positive opinion for the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation. The Company also announced that the FDA has granted priority review for the same patient population. GSK withdrew its first Marketing Authorisation Application for the combo to the European Medicines Agency in March 2014.

The CHMP positive opinion is based on results from the Phase III COMBI-d and COMBI-v studies. The COMBI-d study showed that the combination of Tafinlar and Mekinist achieved a statistically significant overall survival (OS) benefit compared to Tafinlar monotherapy (median of 25.1 months vs 18.7 months). In those who received Tafinlar in combination with Mekinist, OS was 74% at 1 year and 51% at 2 years versus 68% and 42% for those who received Tafinlar only, respectively. The COMBI-v study showed that the combination of Tafinlar and Mekinist achieved a statistically significant OS benefit compared to vemurafenib monotherapy (median for the combination not reached vs 17.2 months). In the COMBI-v study, the rate of OS at 1 year was 72% with the combination of Tafinlar and Mekinist and 65% for those receiving vemurafenib only. The safety results from these studies were consistent with the profile observed to date for the combination; no new safety concerns were observed.

The US FDA granted Priority Review in metastatic melanoma for the supplemental New Drug Application (sNDA) for the combination of Tafinlar and Mekinist, which included data from the COMBI-d and COMBI-v studies. Since January 2014, the combination of Tafinlar and Mekinist has been approved for use in the US in patients with BRAF V600E/K mutation-positive unresectable or metastatic melanoma as detected by an FDA-approved test. The combination was approved through the FDA's Accelerated Approval program and reviewed under a Priority Review designation. The approval was contingent on the results of the COMBI-d study, which was designed to evaluate the clinical benefit of the combination in patients with unresectable or metastatic melanoma with a BRAF V600 mutation. A PDUFA date is in November 2015.