Roche announced that the US Food and Drug Administration (FDA) approved Zelboraf (vemurafenib) for the treatment of BRAF V600E mutation-positive, inoperable or metastatic melanoma, as determined by an FDA-approved test. The FDA also approved the cobas 4800 BRAF V600 Mutation Test, a diagnostic test developed by Roche to identify patients eligible for treatment. Zelboraf is the first and only FDA-approved personalized medicine shown to improve survival in people with BRAF V600E mutation-positive metastatic melanoma, demonstrating the benefits of Roche’s personalized healthcare approach. It is designed to target and inhibit some mutated forms of the BRAF protein found in about half of all cases of melanoma, the deadliest and most aggressive form of skin cancer.

“The FDA approval of Zelboraf marks a major step forward in personalizing the treatment of metastatic melanoma, a devastating disease that until this year had limited approved treatment options,” said Hal Barron, M.D., chief medical officer and head, Global Product Development. “We will continue to study this medicine with a goal of further improving outcomes for people with melanoma and other cancers that are driven by BRAF mutations.”

Zelboraf should be used only in people whose inoperable or metastatic melanoma carries a BRAF V600E mutation, which can be determined by the FDA-approved cobas BRAF Mutation Test.

“The cobas BRAF Mutation Test has improved sensitivity, accuracy and speed compared to other commonly used, unapproved detection methods,” said Paul Brown, head of Roche Molecular Systems. “With a personalized medicine now available, all people diagnosed with inoperable or metastatic melanoma should be tested to help determine the best options for treatment.”

Zelboraf will be available in the United States within two weeks of approval. Roche has also submitted new drug applications for Zelboraf in the EU, Switzerland, Australia, New Zealand, Brazil, India, Mexico and Canada. While Roche seeks regulatory approval of Zelboraf in other countries, a global Expanded Access Program (EAP) is available for people with previously treated or untreated BRAF V600 mutation-positive metastatic melanoma.

The FDA approval of Zelboraf is based on results from two clinical studies (BRIM3 and BRIM2) in people with BRAF V600E mutation-positive, inoperable or metastatic melanoma as determined by the cobas BRAF Mutation Test.

BRIM3 is a global, randomized, open-label, controlled, multicenter, Phase III study that compared Zelboraf to dacarbazine chemotherapy, a standard of care, in 675 patients with previously untreated BRAF V600E mutation-positive, unresectable (inoperable) or metastatic melanoma. The endpoints of BRIM3 were overall survival (OS) and investigator-assessed progression-free survival (PFS). Other endpoints included confirmed investigator-assessed overall response rate. BRIM2 is a global, single-arm, multicenter, open-label phase II study that enrolled 132 patients with previously treated BRAF V600E mutation-positive, unresectable or metastatic melanoma. The primary endpoint of BRIM2 was confirmed overall response rate as assessed by independent review.

In BRIM3, the risk of death was reduced by 56 per cent for people who received Zelboraf compared to those who received chemotherapy (hazard ratio [HR]=0.44, p<0.0001). At the time of the analysis, median overall survival of patients receiving Zelboraf had not been reached and was 7.9 months for those receiving chemotherapy.

People who received Zelboraf also had a 74 per cent reduced risk of the disease getting worse or dying (PFS) compared to those who received chemotherapy (HR=0.26, p<0.0001). Median PFS was 5.3 months for those who received Zelboraf compared to 1.6 months for those who received chemotherapy.

The confirmed investigator-assessed response rate (those who experienced tumour shrinkage) in people who received Zelboraf was 48.4 per cent (1 percent complete responses and 47.4 per cent partial responses) compared to 5.5 per cent (partial responses) for those who received chemotherapy (p<0.0001).

BRIM2: Previously Treated BRAF V600E Mutation-Positive, Unresectable or Metastatic Melanoma

In BRIM2, Zelboraf shrank tumours in 52 per cent of trial participants.

Zelboraf is an oral, small molecule, kinase inhibitor indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test. Zelboraf is not recommended for use in melanoma patients who lack the BRAF V600E mutation. Zelboraf is being co-developed under a 2006 license and collaboration agreement between Roche and Plexxikon, a member of the Daiichi Sankyo Group.

Roche and Genentech are conducting a broad development program with Zelboraf that includes testing combinations with other medicines (both approved and investigational, from Roche/Genentech and other companies), as well as studies in other tumor types. While Roche seeks approval of Zelboraf outside of the United States, Zelboraf is available to eligible patients with BRAF V600 mutation-positive metastatic melanoma through a global EAP. More information about this program or other Zelboraf studies is available at the Roche Clinical Trials Registry at www.roche-trials.com (in the EU) or www.clinicaltrials.gov (in the United States).

Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics.