The European Commission (EC) has granted marketing authorisation for GlaxoSmithKline’s Mekinist (trametinib) as a single agent in the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation.

Trametinib has not demonstrated clinical activity in patients who have progressed on a prior BRAF inhibitor therapy. Before taking trametinib, patients must have confirmation of a BRAF V600 mutation using a validated test.

Trametinib is a MEK inhibitor which blocks the activity of a protein kinase called MEK. This protein is present in the MAPK pathway, which regulates the normal growth and death of cells and plays a role in metastatic melanoma development. Some mutations in the BRAF gene can cause the MEK protein to stimulate cancer cell growth and survival; therefore, inhibiting MEK can potentially slow down the growth of tumours in BRAF-mutant metastatic melanoma.

Dr. Paolo Paoletti, president of oncology, GSK said: “We welcome today’s decision of the European Commission. MEK has been pursued as a therapeutic target in cancer for more than a decade, and Mekinist is the first medicine in this class to be licensed in Europe.”

The EC decision is based on results from the randomised, open-label phase III METRIC study of 322 patients with BRAF-mutant melanoma (types V600E and V600K) who were treatment-naïve or may have received one prior chemotherapy treatment in the metastatic setting. In this study, the treatment with trametinib resulted in a statistically significant increase in progression-free survival (PFS) compared to chemotherapy (HR= 0.45; [95% CI: 0.33, 0.63], p<0.0001) with a median PFS of 4.8 months for patients taking trametinib (95% CI: 4.3, 4.9) compared to 1.5 months for chemotherapy (95% CI: 1.4, 2.7).

The regulatory submission to the European authorities also included a single-arm Phase II study designed to evaluate the objective response rate, safety, and pharmacokinetics of trametinib at 2.0 mg once daily in patients with BRAF V600E, V600K, or V600D mutation-positive metastatic melanoma. In this study, 97 patients with BRAF-mutant melanoma were split in two cohorts: previously treated or not treated with a BRAF inhibitor.

The safety of trametinib has been evaluated in the integrated safety population of 329 patients with metastatic melanoma. Of these patients, 211 patients were treated with trametinib for BRAF V600-mutant melanoma in a randomised, open-label Phase III study. The most common adverse reactions (=20%) for trametinib include rash, diarrhoea, fatigue, oedema peripheral (fluid in the legs and feet), nausea, and dermatitis acneiform (an acne-like skin condition).

Mekinist was in-licensed by GSK in 2006. GSK holds the worldwide exclusive rights to develop, manufacture and commercialise Mekinist, while Japan Tobacco retains co-promotion rights in Japan.