Zelboraf is approved for metastatic tumors that express the BRAF V600E mutation.

FDA approved Roche’s Zelboraf (vemurafenib) to treat patients with late-stage or unresectable melanoma alongside a companion diagnostic that was also developed by Roche. Zelboraf is specifically indicated for the treatment of patients with melanoma whose tumors express a gene mutation called BRAF V600E. The drug has not been studied in patients whose melanoma tests negative for that mutation by an FDA-approved diagnostic.

The companion test, cobas 4800 BRAF V600 Mutation Test, will help determine if a patient’s melanoma cells have the BRAF V600E mutation. The BRAF protein is normally involved in regulating cell growth but is mutated in about half the patients with late-stage melanomas, according to Roche. Zelboraf is a BRAF inhibitor that is able to block the function of the V600E-mutated BRAF protein.

“This has been an important year for patients with late-stage melanoma. Zelboraf is the second new cancer drug approved that demonstrates an improvement in overall survival,” said Richard Pazdur, M.D., director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research. “In March, we approved Yervoy (ipilimumab), another new treatment for late-stage melanoma that also showed patients live longer after receiving the drug.” Yervoy is a developed by Bristol-Myers Squibb.

Zelboraf is marketed by Genentech, a member of the Roche Group. The cobas 4800 BRAF V600 Mutation Test is manufactured by Roche Molecular Systems. The drug was reviewed under the FDA’s priority review program that provides for an expedited six-month review of drugs. Zelboraf and the companion BRAF V600E test are being approved ahead of the drug’s October 28, 2011, goal date and the companion diagnostics’ November 12, 2011, deadline.

Zelboraf’s safety and effectiveness were established in a single international trial of 675 patients with late-stage melanoma with the BRAF V600E mutation who had not received prior therapy. Patients were assigned to receive either Zelboraf or dacarbazine, another anticancer therapy. The trial was designed to measure overall survival. The median survival of patients receiving Zelboraf has not been reached (77% still living), while the median survival for those who received dacarbazine was 8 months (64% still living).

“Today’s approval of Zelboraf and the cobas test is a great example of how companion diagnostics can be developed and used to ensure patients are exposed to highly effective, more personalized therapies in a safe manner,” notes Alberto Gutierrez, Ph.D., director of the Office of In Vitro Diagnostic Device Evaluation and Safety in the FDA’s Center for Devices and Radiological Health.

The FDA’s approval of the cobas 4800 BRAF V600 Mutation Test was based on data from the clinical study that also evaluated the safety and effectiveness of Zelboraf. Samples of a patient’s melanoma tissue were collected to test for the mutation.

The most common side effects reported in patients receiving Zelboraf included joint pain, rash, hair loss, fatigue, nausea, and skin sensitivity when exposed to the sun. About 26% of patients developed a skin-related cancer called cutaneous squamous cell carcinoma, which was reportedly managed with surgery.

In July FDA issued a new draft guidance to facilitate the development and review of companion diagnostics. The guidance, currently available for public comment, is intended to provide companies with details on the agency’s policy for reviewing a companion diagnostic and the corresponding drug therapy.

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