GlaxoSmithKline plc (LSE/NYSE: GSK) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending marketing authorisation for Mekinist™(trametinib) as a single agent in the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation. Trametinib as a single agent has not demonstrated clinical activity in patients who have progressed on a prior BRAF inhibitor therapy. Before taking trametinib, patients must have confirmation of BRAF V600 mutation using a validated test.
Dr Rafael Amado, Head of Oncology R&D at GSK said: “This CHMP opinion brings us a step closer to making another personalised medicine available for patients with BRAF-mutant metastatic melanoma in Europe.”
The CHMP recommendation for trametinib monotherapy is based on a randomised open label phase III study comparing trametinib to chemotherapy in 322 patients with BRAF mutant melanoma (V600E and V600K) and a non-randomised phase II study in 97 patients with BRAF mutant melanoma split in two cohorts: previously treated or not treated with a BRAF inhibitor.
A CHMP positive opinion is one of the final steps before marketing authorisation is granted by the European Commission (EC), but does not always result in marketing authorisation. A final decision by the EC is anticipated during the second quarter of 2014.
Mekinist is a MEK inhibitor that targets the MAPK pathway, which regulates the normal growth and death of cells, including skin cells and plays a role in metastatic melanoma development.
Mekinist is approved as a single agent and in combination with Tafinlar (dabrafenib) in the US and Australia. Mekinist is also approved as monotherapy in Canada. Detailed prescribing information, which may differ between the countries, can be accessed:
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.
Safety information for Mekinist (trametinib)
The most common adverse reactions (≥ 20 %) for Mekinist include rash, diarrhoea, fatigue, oedema peripheral, nausea, and dermatitis acneiform. Special warnings and precautions for use of trametinib include:
Left ventricular ejection fraction (LVEF) reduction/Left ventricular dysfunction (cardiac disorders)
Trametinib has been reported to decrease LVEF.
Elevations in blood pressure have been reported in association with trametinib in patients with or without pre-existing hypertension.
Interstitial lung disease (ILD)/Pneumonitis
In a Phase 3 trial, 2.4 % (5/211) of patients treated with trametinib developed ILD or pneumonitis; all five patients required hospitalisation.
Haemorrhage (symptomatic bleeding in a critical area or organ)
Haemorrhagic events, including major haemorrhagic events (defined as symptomatic bleeding in a critical area or organ), have occurred in patients taking trametinib. The risk of haemorrhage may be increased with concomitant use of antiplatelet or anticoagulant therapy.
Rhabdomyolysis (damage of skeletal muscle tissue)
Rhabdomyolysis has been reported in patients taking trametinib. In some cases, patients were able to continue trametinib. In more severe cases hospitalisation, interruption or permanent discontinuation of trametinib was required.
Disorders associated with visual disturbance, including retinal pigment epithelial detachment (RPED) and retinal vein occlusion (RVO), have been observed with trametinib. Symptoms such as blurred vision, decreased acuity, and other visual phenomena have been reported in the clinical trials with trametinib.
In clinical studies with trametinib, rash has been observed in about 60 % of patients.
Hepatic events (liver-related)
Hepatic adverse events have been reported in clinical trials with trametinib
As metabolism and biliary excretion are the primary routes of elimination of trametinib, administration of trametinib should be undertaken with caution in patients with moderate to severe hepatic impairment.
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Cautionary statement regarding forward-looking statements
GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D ‘Risk factors’ in the company’s Annual Report on Form 20-F for 2013.