GlaxoSmithKline plc [announced today that the U.S. Food and Drug Administration (FDA) has approved both TAFINLAR® (dabrafenib) and MEKINIST™ (trametinib). Tafinlar is indicated as a single-agent oral treatment for unresectable melanoma (melanoma that cannot be removed by surgery) or metastatic melanoma (melanoma which has spread to other parts of the body) in adult patients with BRAF V600E mutation. Tafinlar is not indicated for the treatment of patients with wild-type BRAF melanoma. Mekinist is indicated as a single-agent oral treatment for unresectable or metastatic melanoma in adult patients with BRAF V600E or V600K mutations. Mekinist is not indicated for the treatment of patients who have received a prior BRAF inhibitor therapy. These mutations must be detected by an FDA-approved test, such as the companion diagnostic assay from bioMérieux S.A., THxID™-BRAF. “With today’s FDA approvals, GSK can now offer two new single-agent therapies to selected patients who have metastatic melanoma, a devastating disease with very low survival rates and few treatment options,” said Paolo Paoletti, M.D., President, GlaxoSmithKline Oncology. “GSK Oncology has been focused on progressing research in the most efficient manner possible, and we’re pleased to bring Tafinlar and Mekinist to physicians and their patients in rapid development times.” Among those with metastatic melanoma, approximately half have a BRAF mutation, which is an abnormal change in a gene that can enable some melanoma tumours to grow and spread.[i]Tafinlar and Mekinist are each approved for patients with the BRAF V600E mutation, which accounts for approximately 85 percent of all BRAF V600 mutations in metastatic melanoma.
Mekinist is also approved for patients with the V600K mutation, which makes up approximately 10 percent of all BRAF V600 mutations in metastatic melanoma.“MEK has been pursued as a therapeutic target in cancer for more than a decade,” said Keith Flaherty, M.D., Director of Developmental Therapeutics, Massachusetts General Hospital Cancer Center, and principal investigator of the Phase III METRIC trial. “Based on the clear improvement versus chemotherapy in progression-free survival, trametinib represents the first validated MEK inhibitor. We welcome it as a new treatment option for patients with this disease.”As part of the FDA approval, which was based on clinical studies evaluating the efficacy and safety of these products, warnings and precautions were also identified. Dabrafenib can cause serious side effects, some of which can be life threatening, including increasing the risk of developing new primary cutaneous malignancies (new skin cancers), tumour promotion in BRAF wild-type melanoma, serious febrile drug reactions (severe fevers), hyperglycaemia (blood sugar problems), uveitis and iritis (severe eye problems), haemolytic anaemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency and embryofoetal toxicity (potential harm to the unborn baby in pregnant women). Trametinib can cause serious side effects, some of which can be life threatening, including cardiomyopathy (heart problems, including heart failure), retinal pigment epithelial detachment (RPED) and retinal vein occlusion (RVO) (eye problems including blindness), interstitial lung disease or pneumonitis (lung or breathing problems), serious skin toxicity (rash) and embryofoetal toxicity. GSK will be making Tafinlar and Mekinist available for prescription no later than in the early third quarter of 2013. In 2010, GSK entered a collaboration with bioMérieux to develop a companion diagnostic test to detect BRAF V600 (V600E and V600K) gene mutations found in several cancers, including melanoma. bioMérieux has received FDA pre-market approval of THxID™-BRAF. Currently, it is the only FDA-approved test that detects the V600K mutation.