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Two new drugs extend survival for melanoma patients
 
 
  FDA OKs Late-Stage Melanoma Drug

MedPage Today

Published: August 17, 2011

WASHINGTON -- The FDA has approved vemurafenib (Zelboraf) for the treatment of metastatic and unresectable melanoma along with a companion genetic mutation test.

Vemurafenib is specifically indicated for patients whose tumors express a BRAF V600E mutation, the FDA said in a statement. The companion diagnostic tool, known as the cobas 4800 BRAF V600 Mutation Test, can help determine if the melanoma cells contain the indicated mutation.

Vemurafenib is a BRAF inhibitor that blocks the function of the V600E-mutated BRAF protein. The drug has not been studied in patients who test negative for the BRAF V600E mutation, the FDA stated.

Vemurafenib is the second drug approved for late-stage melanoma this year; ipilimumab (Yervoy) was approved by the FDA in March.

The safety and efficacy of vemurafenib were determined in a trial of 675 patients with late-stage melanoma who had the BRAF V600E mutation. They had not received prior therapy. Patients were assigned to vemurafenib or dacarbazine. The endpoint was overall survival.

The median survival for vemurafenib has not yet been reached, with 77% of patients still alive versus a median survival of eight months in the dacarbazine group, with 64% of patients still alive, the statement said.

Adverse events in the trial included joint pain, rash, hair loss, fatigue, nausea, and skin sensitivity to sunlight. Additionally, roughly 26% of patients developed cutaneous squamous cell carcinoma, which was managed with surgery.

Approval for the companion mutation test was based on data from the same safety and efficacy trial. Samples from melanoma tissue were collected to test for the BRAF V600E mutation.

Vemurafenib received FDA priority review, which is given to drugs that may offer major advances in therapy, or treatment where inadequate treatment is available.

Monthly costs for vemurafenib treatment will be $9,400. The total cost will be $56,400 for the estimated six months of treatment time, a representative from drugmaker Genentech said. The genetic mutation test will cost from $120 to $150.

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August 17, 2011, 5:24 pm

Fast F.D.A. Approval of Melanoma Drug

NY Times Blog By DUFF WILSON

The Food and Drug Administration approved an expensive new melanoma drug much faster than expected, giving a boost not only to that drug but also to other experimental products that may offer gene-based personalized medicine.

The F.D.A. approved vemurafenib, with the brand name Zelboraf, to treat patients with metastatic melanoma who have a certain genetic mutation called BRAF V600E. The drug inhibits the cancer-spreading action of that particular gene, which is held in about 50 percent of people who have metastatic melanoma.

The F.D.A. also approved a test for the genetic mutation.

Roche Holding said the drug would be available in about two weeks at a price of $9,800 a month. The drug will be sold by Genentech of San Francisco, a subsidiary of Roche of Switzerland, and Daiichi Sankyo of Japan.

Roche sought approval in May under an expedited review process for drugs that may offer major advances. The F.D.A. was expected to act by Oct. 28. Its approval came more than two months early - a vote of confidence by an agency that has been accused of failing to act promptly on some other drugs.

The fast action may portend well for crizotinib, a proposed lung cancer drug from Pfizer shown to be effective in the estimated 3 to 5 percent of non-small cell lung cancer patients whose tumors have a certain gene. That, too, was submitted with a diagnostic gene test. It is still under review.

In March, the F.D.A. approved another new drug for late-stage melanoma, called Yervoy, from Bristol-Myers Squibb. It acts on the immune system. Bristol-Myers Squibb charges $120,000 for a course of treatment.

Clinical trial results on the two drugs were released at the annual meeting of the American Society of Clinical Oncology, to the acclaim of skin cancer doctors.

"This has been an important year for patients with late-stage melanoma," Dr. Richard Pazdur, director of the F.D.A. Office of Oncology Drug Products, said in a press release on Wednesday.

But it is far from a cure.

"The F.D.A.'s quick action on this drug approval is important because it gives melanoma patients a new way to fight this deadly disease," Timothy J. Turnham, executive director of the Melanoma Research Foundation, said in a statement. But many patients become resistant, he added, and the drug prolongs lives only months on average, pointing to the need for further research.

Side effects of Zelboraf may include joint pain, rash, hair loss, fatigue, nausea, skin sensitivity when exposed to the sun, and another skin-related cancer that can be managed with surgery.

Melanoma is the deadliest skin cancer. About 8,700 people died of it in the United States last year and 68,000 were newly diagnosed, according to the National Cancer Institute.

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FDA NEWS RELEASE

For Immediate Release: Aug. 17, 2011

Media Inquiries: Erica Jefferson, 301-796-4988, erica.jefferson@fda.hhs.gov

Consumer Inquiries: 888-INFO-FDA

FDA approves Zelboraf and companion diagnostic test for late-stage skin cancer

Second melanoma drug approved this year that improves overall survival


The U.S. Food and Drug Administration today approved Zelboraf (vemurafenib), a drug to treat patients with late-stage (metastatic) or unresectable (cannot be removed by surgery) melanoma, the most dangerous type of skin cancer.

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.

Zelboraf is being approved with a first-of-a-kind test called the cobas 4800 BRAF V600 Mutation Test, a companion diagnostic that 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 of the patients with late-stage melanomas. 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."

Zelboraf was reviewed under the FDA's priority review program that provides for an expedited six-month review of drugs that may offer major advances in treatment or that provide a treatment when no adequate therapy exists. Zelboraf and the companion BRAF V600E test are being approved ahead of the drug's Oct. 28, 2011 goal date and the companion diagnostics' Nov. 12, 2011 goal date.

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 anti-cancer therapy. The trial was designed to measure overall survival (the length of time between start of treatment and death of a patient).

The median survival (the length of time a patient lives after treatment) of patients receiving Zelboraf has not been reached (77 percent still living) while the median survival for those who received dacarbazine was 8 months (64 percent 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," said 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 percent of patients developed a skin-related cancer called cutaneous squamous cell carcinoma, which was managed with surgery. Patients treated with Zelboraf should avoid sun exposure.

Zelboraf is being approved with a Medication Guide to inform health care professionals and patients of Zelboraf's potential risks.

In July 2011, the 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 guidance on the agency's policy for reviewing a companion diagnostic and the corresponding drug therapy.

Melanoma is the leading cause of death from skin disease. The National Cancer Institute estimated that 68,130 new cases of melanoma were diagnosed in the United States during 2010; about 8,700 people died from the disease.

Zelboraf is marketed by South San Francisco based-Genentech, a member of the Roche Group. The cobas 4800 BRAF V600 Mutation Test is manufactured by Roche Molecular Systems in Pleasanton, Calif.

 
 
 
 
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