EU Approval For Tafinlar® and Mekinist®

This is the first targeted therapy combination approved in the EU to treat patients with the most aggressive form of skin cancer, demonstrating improved overall survival versus the current standard of care with BRAF inhibitor monotherapy in two Phase III studies.

"We look forward to making the Tafinlar and Mekinist targeted combination treatment, which demonstrated a significant overall survival benefit in two robust clinical trials, available across Europe as soon as possible," said Bruno Strigini, President, Novartis Oncology. "Today's EU approval further demonstrates our ongoing commitment to deliver medicines that can further enhance outcomes for patients with metastatic melanoma." 

Metastatic melanoma is the most serious and life-threatening type of skin cancer and is associated with low survival rates; approximately one out of every five people will survive for five years following a diagnosis with late-stage disease. There are about 200,000 new cases of melanoma diagnosed worldwide each year, approximately half of which have BRAF mutations. Gene tests can determine whether a tumor has a BRAF mutation, and results can play a key role in prognosis and determining appropriate treatment. 

Marketing authorization is based on results from the Phase III COMBI-d and COMBI-v studies, in which the Tafinlar/Mekinist combination demonstrated overall survival (OS) benefit compared to Tafinlar and Zelboraf monotherapies respectively in patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. 

The COMBI-d study showed that the combination of Tafinlar and Mekinist achieved a statistically significant OS benefit compared to Tafinlar monotherapy (median of 25.1 months vs 18.7 months; Hazard Ratio [HR] 0.71 [95% Confidence Interval (CI), 0.55-0.92], p=0.011). 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. Safety results from the COMBI-d study were consistent with the profile observed to date for the combination; no new safety concerns were observed. The most common adverse events (>=20%) in the combination arm were pyrexia, fatigue, nausea, headache, chills, diarrhea, rash, joint pain (arthralgia), hypertension, vomiting, cough, and peripheral edema. Adverse events or toxicities were generally manageable with appropriate intervention, as described in the product labelling submitted with the application. Updated results from COMBI-v will be presented at an upcoming medical congress.

The European Commission approval applies to all 28 EU member states, plus Iceland, Norway and Liechtenstein.

In the US, the Food and Drug Administration (FDA) granted priority review in July 2015 for regular approval of the Tafinlar and Mekinist combination in BRAF V600 mutation-positive metastatic melanoma. 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.