GSK receives EU marketing authorisation for Mekinist™ (trametinib) for patients with unresectable or metastatic melanoma with a BRAF V600 mutation

Issued: London UK

GlaxoSmithKline plc (LSE/NYSE: GSK) today announced that the European Commission (EC) has granted 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 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.^[1]

Trametinib is a MEK inhibitor which blocks the activity of a protein kinase called MEK.¹ 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;[2] 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).¹

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.¹

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).¹

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)¹

Trametinib has been reported to decrease LVEF.

Hypertension¹

Elevations in blood pressure have been reported in association with trametinib in patients with or without pre-existing hypertension.

Interstitial lung disease (ILD)/pneumonitis¹

In a Phase III trial, 2.4% (5/211) of patients treated with trametinib developed ILD or pneumonitis; all five patients required hospitalisation.

Haemorrhage¹

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)¹

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.

Visual impairment¹

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.

Rash¹

In clinical studies with trametinib, rash has been observed in about 60% of patients.

Hepatic events (liver-related)¹

Hepatic adverse events have been reported in clinical trials with trametinib.

Hepatic impairment¹

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.

GSK – one of the world’s leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer.  For further information please visit www.gsk.com.

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.

References

[1]   Mekinist EU Summary of Product Characteristics. 2014.

[2]   Romano E, Schwartz GK, Chapman PB, et al. “Treatment implications of the emerging molecular classification system for melanoma.” Lancet Oncol. 2011;12(9):913-22.