Dabrafenib: First Global Approval

Dabrafenib (Tafinlar®), a mutant-BRAF kinase inhibitor, emerged from GlaxoSmithKline’s research programme for the discovery of selective inhibitors of mutant BRAF kinase activity, for the treatment of solid tumours; mutations in the BRAF gene are associated with increased growth and proliferation of cancer cells. GlaxoSmithKline has focused the development of dabrafenib on the treatment of malignant melanoma, as BRAF mutations are present in 50 % of these cancers. Dabrafenib is approved in the US as a single agent treatment for unresectable or metastatic melanoma in patients with the BRAF V600E mutation, and has received a positive opinion in the EU in this indication. Submissions have also been made in the US and the EU for the use of dabrafenib in combination with trametinib for the treatment of metastatic melanoma with a BRAF V600E/K mutation. Global phase III development of dabrafenib as a monotherapy and as a combination therapy is ongoing in the treatment of malignant melanoma. Phase II development is ongoing for the treatment of malignant melanoma that has metastasised to the brain, and for colorectal and non-small cell lung cancers. Dabrafenib is intended to treat the patient population with a BRAF V600E/K mutation. GlaxoSmithKline’s dabrafenib application in the US included the treatment of this population as detected by a US FDA-approved test. GlaxoSmithKline, in collaboration with bioMérieux and Response Genetics, has developed a molecular theranostic test to identify BRAF V600E/K mutations. Pre-Market approval of the test has been granted by the FDA. This article summarises the milestones in the development of dabrafenib leading to this first approval as a single agent treatment for unresectable or metastatic melanoma in patients with the BRAF V600E mutation.