EMA Recommends Granting a Marketing Authorisation for Trametinib and Extending Indications for Sorafenib

Trametinib is intended for patients with unresectable or metastatic melanoma with a BRAF V600 mutation and sorafenib for patients with progressive, locally-advanced or metastatic, differentiated thyroid cancer

On 25 April 2014, the European Medicines Agency Committee for Medicinal Products for Human Use (CHMP) has recommended granting a marketing authorisation for trametinib (Mekinist) for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation. The CHMP has also recommended adding a new indication to the use of the cancer medicine sorafenib (Nexavar) to treat patients with papillary/follicular/Hürthle cell thyroid carcinoma, refractory to radioactive iodine.

Trametinib for the treatment of unresectable or metastatic melanoma with a BRAF V600 mutation

The CHMP adopted a positive opinion, recommending the granting of a marketing authorisation for the medicinal product trametinib (Mekinist), 0.5, 1 and 2 mg, film-coated tablet intended for the treatment of unresectable or metastatic melanoma with a BRAF V600 mutation.

The applicant for this medicinal product is Glaxo Group Ltd. They may request a re-examination of any CHMP opinion, provided they notify the European Medicines Agency in writing of their intention within 15 days of receipt of the opinion.

The active substance of Mekinist is trametinib, a protein kinase inhibitor (L01XE25) that inhibits mitogen-activated extracellular signal regulated kinase 1 (MEK1) and MEK2 activation and kinase activity.

The benefits with trametinib are its ability to improve overall survival and progression-free survival in melanoma patients with a BRAF V600 mutation compared to chemotherapy.

The most common side effects are rash, diarrhoea, fatigue, peripheral oedema, nausea, and dermatitis acneiform.

A pharmacovigilance plan for peripheral will be implemented as part of the marketing authorisation.

The approved indication is: "Trametinib is indicated for 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."

It is proposed that trametinib be initiated and supervised by a physician experienced in the administration of anti-cancer medicinal products.

Detailed recommendations for the use of this product will be described in the summary of product characteristics, which will be published in the European public assessment report and made available in all official European Union languages after the marketing authorisation has been granted by the European Commission.

The CHMP, on the basis of quality, safety and efficacy data submitted, considers there to be a favourable benefit-to-risk balance for trametinib and therefore recommends the granting of the marketing authorisation.

Sorafenib for treatment of progressive, locally-advanced or metastatic papillary/follicular/Hürthle cell thyroid carcinoma, refractory to radioactive iodine

The CHMP adopted a positive opinion recommending a variation to the terms of the marketing authorisation for the medicinal product sorafenib (Nexavar). The marketing authorisation holder for this medicinal product is Bayer Pharma AG.

Sorafenib is currently indicated for the treatment of patients with hepatocellular carcinoma and for the treatment of patients with advanced renal cell carcinoma who have failed prior interferon-alpha or interleukin-2 based therapy or are considered unsuitable for such therapy.

The CHMP has now recommended an extension to the indication to include the treatment of patients with progressive, locally-advanced or metastatic, differentiated thyroid carcinoma, refractory to radioactive iodine.

The full indication for Nexavar will be:

Hepatocellular carcinoma

Nexavar is indicated for the treatment of hepatocellular carcinoma.

Renal cell carcinoma

Nexavar is indicated for the treatment of patients with advanced renal cell carcinoma who have failed prior interferon-alpha or interleukin-2 based therapy or are considered unsuitable for such therapy.

Differentiated thyroid carcinoma

Nexavar is indicated for the treatment of patients with progressive, locally advanced or metastatic, differentiated (papillary/follicular/Hürthle cell) thyroid carcinoma, refractory to radioactive iodine.”

Detailed conditions for the use of this product will be described in the updated summary of product characteristics, which will be published in the revised European public assessment report, and will be available in all official European Union languages after the variation to the marketing authorisation has been granted by the European Commission.