GlaxoSmithKline’s Dabrafenib and Trametinib Approved by the FDA for Metastatic Melanoma

May 29, 2013 | By Márcio Barra

Today, two new drugs from GSK were approved by the FDA, dabrafenib (Tafinlar) and trametinib (Mekinist), for use in certain patients with metastatic or unresectable melanoma, alongside a diagnostic test to identify patients who are most likely to respond to these treatments.

Dabrafenib is a BRAF – a proto oncogene with more than 30 mutations associated to cancer –  inhibitor, designed to attack tumors that express the BRAF V600E gene mutation. It is from the same class as the first BRAF inhibitor, Zelboraf, an oral, small molecule, kinase inhibitor from Roche and Genentech approved in 2011.

Trametinib is a mitogen-activated, extracellular signal-regulated kinase inhibitor MEK inhibitor, targeting tumors that express the BRAF V600E or V600K gene mutations.

The THxID BRAF diagnostic test, developed in collaboration with bioMérieux, will help determine if a patient’s melanoma cells have the V600E or V600K mutation in the BRAF gene, thus determining if the patient is eligible for treatment with GSK’s two new drugs.

In FDA’s press release, the agency noted that dabrafenib and trametinib were approved separately for use as monotherapy, not as a combination, through evaluation of the METRIC (Trametinib)  and BREAK 3 (Dabrafenib) pivotal trials.  Therapy with both drugs together has been tested clinically, and GlaxoSmithKline is now conducting a phase 3 study, COMBI-AD, to test the combination of dabrafenib and trametinib in patients with BRAF V600 melanoma that has been completely removed by surgery.

Both drugs carry a heavy side effect profile to the user, but preliminary results from the COMBI-AD study suggests that the use of the two drugs together results in less toxicity for the patient. Zelboraf, Genentech’s BRAF inhibitor, had a high occurrence rate of skin toxicities, like keratoacanthomas, which are unusual occurrences with dabrafenib. However, dabrafenib provoked pyrexia reactions in a large percentage of patients in the clinical trials, something not seen with Zelboraf.


Fierce Biotech – FDA’s press release

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