Tafinlar and Mekinist combination therapy achieves regulatory milestones

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion for the combination of Novartis’ Tafinlar® (dabrafenib) and Mekinist® (trametinib) for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation.

Novartis also announced that the US Food and Drug Administration (FDA) has granted priority review for the same patient population.

“The CHMP positive opinion and FDA priority review of Tafinlar and Mekinist validate the importance of this targeted therapy combination for patients with the most serious form of skin cancer,” said Bruno Strigini, President, Novartis Oncology. “This good news for the combination of Tafinlar and Mekinist in metastatic melanoma follows on the FDA’s recent Breakthrough Therapy designation for the combination in BRAF V600 mutation-positive non-small cell lung cancer. We look forward to working with the US and EU regulatory authorities to help bring this targeted therapy combination to more patients who may benefit.”

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. The COMBI-v study showed that the combination of Tafinlar and Mekinist achieved a statistically significant OS benefit compared to vemurafenib monotherapy. The safety results from these studies were consistent with the profile observed to date for the combination; no new safety concerns were observed.

The European Commission will review the CHMP recommendation and is expected to deliver its final decision within three months.

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 programme and reviewed under a Priority Review designation. The approval was contingent on the results of the COMBI-d study. A PDUFA date is in November 2015.

Tafinlar Mekinist combination also granted Breakthrough Therapy designation for NSCLC

The latest actions closely follow FDA Breakthrough Therapy designation for Tafinlar and Mekinist in BRAF V600 mutation-positive non-small cell lung cancer (NSCLC). The Breakthrough Therapy designation in BRAF V600 mutation-positive NSCLC is based on interim analysis results from an ongoing single-arm, two-stage, Phase II trial investigating the Tafinlar and Mekinist combination in patients with metastatic NSCLC who had the BRAF V600E mutation and failed at least one line of chemotherapy. The data showed an overall response rate (ORR) of 63% based on investigator assessment.

Tafinlar and Mekinist in combination for NSCLC is the sixth Breakthrough Therapy designation for Novartis.