The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending approval of encorafenib and binimetinib in combination for the treatment of adult patients with unresectable or metastatic melanoma with a BRAFV600 mutation.
The CHMP recommendation will now be reviewed by the European Commission (EC), which has the authority to approve medicines for the European Union (EU).
The decision will be applicable to all 28 EU member states plus Liechtenstein, Iceland and Norway.
The CHMP positive opinion is based on results from the Phase 3 COLUMBUS trial, which demonstrated that the combination improved median progression-free survival (PFS), compared with vemurafenib alone (14.9 months versus 7.3 months, respectively: hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.41–0.71; p<0.0001).
As presented at the American Society of Clinical Oncology (ASCO) in June 2018, treatment with encorafenib and binimetinib achieved a median overall survival (OS) of 33.6 months, compared with 16.9 months for patients treated with vemurafenib as a monotherapy (HR 0.61, 95% CI, 0.47–0.79; p<0.0001) in the planned analysis of OS in the COLUMBUS trial.
Adverse events leading to discontinuation that were suspected to be related to the study treatment occurred in 6% of patients.
The most common Grade 3–4 adverse events, seen in more than 5% of patients, were: increased gamma-glutamyltransferase (9%), increased creatine phosphokinase (7%) and hypertension (6%).
Important safety information and recommendations for the use of encorafenib and binimetinib will be detailed in the summary of product characteristics (SmPC), which will be published in the European Public Assessment Report (EPAR) and made available in all official EU languages if marketing authorisation is granted by the EC.
On 27 June 2018, Pierre Fabre’s partner Array BioPharma, which has exclusive rights for these medicines in the United States (US), announced that encorafenib and binimetinib were approved by the Food and Drug Administration (FDA) in the US for the treatment of unresectable or metastatic melanoma with a BRAFV600E or BRAFV600K mutation, as detected by an FDA-approved test.
Encorafenib is not indicated for treatment of patients with wild-type BRAF melanoma.
Encorafenib and binimetinib are investigational medicines and are not currently approved in any other country outside of the US.
Applications for marketing authorisation for encorafenib and binimetinib in other countries are currently under review.
"We are delighted to be one step closer to bringing encorafenib and binimetinib to patients with advanced BRAF-mutant melanoma in Europe,” said Frédéric Duchesne, President & CEO of the Pierre Fabre Pharmaceuticals Division. “If the European Commission approves encorafenib and binimetinib, this will be a new treatment option for these patients who currently have a challenging prognosis.”