FDA Approves Zelboraf (Vemurafenib) and Companion Diagnostic for BRAF Mutation-Positive Metastatic Melanoma, a Deadly Form of Skin Cancer - Genentech press release
-- First and Only Personalized Medicine Shown to Help People With BRAF V600E Mutation-Positive Metastatic Melanoma, Found in Half of Melanoma Patients, Live Longer --|
South San Francisco, Calif. -- August 17, 2011 -- Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the U.S. Food and Drug Administration (FDA) approved ZelborafTM (vemurafenib) for the treatment of BRAF V600E mutation-positive, inoperable or metastatic melanoma, as determined by an FDA-approved test. The FDA today 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 and will be distributed through specialty pharmacies (mail-order pharmacies). For more information about Zelboraf distribution, doctors can contact Zelboraf Access Solutions (http://www.GenentechAccessSolutions.com or 1-888-249-4918). Zelboraf Access Solutions also provides doctors and patients coverage and reimbursement support, patient assistance and information resources.
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.
Zelboraf Efficacy in BRAF V600E 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.
BRIM3: Previously Untreated BRAF V600E Mutation-Positive Unresectable or Metastatic Melanoma
* In BRIM3, the risk of death was reduced by 56 percent for people who received Zelboraf compared to those who received chemotherapy (hazard ratio [HR]=0.44, p<0.0001). At the time of 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 percent 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 tumor shrinkage) in people who received Zelboraf was 48.4 percent (1 percent complete responses and 47.4 percent partial responses) compared to 5.5 percent (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 tumors in 52 percent of trial participants.
Important Safety Information for Zelboraf
This information does not take the place of the patient talking to their doctor about their medical condition or their treatment with Zelboraf.
Zelboraf is a prescription medicine used to treat a type of skin cancer called melanoma that has spread to other parts of the body or cannot be removed by surgery, and has a certain type of abnormal "BRAF" gene.
Zelboraf may cause a type of skin cancer called cutaneous squamous cell carcinoma (cuSCC) that usually does not spread to other parts of the body. Patients should check their skin and tell their doctor about skin changes including a new wart, a skin sore or reddish bump that bleeds or does not heal, or a mole that changes size or color.
While taking Zelboraf, patients should avoid going out in the sun. When patients go outside, they should wear clothes that protect their skin, including head, face, hands, arms and legs. They should use lip balm and a broad-spectrum sunscreen with SPF 30 or higher.
Possible serious side effects of Zelboraf include severe allergic reactions; severe skin reactions; changes in the electrical activity of the heart called QT prolongation, which can potentially be life-threatening; abnormal liver function tests; eye problems; or new melanoma lesions.
Common side effects of Zelboraf include joint pain, rash, hair loss, tiredness, sunburn or sun sensitivity, nausea, itching, or warts.
These are not all of the possible side effects of Zelboraf. Patients must tell their doctor if they have any side effect that bothers them or does not go away. For more information about side effects, patients should ask their doctor or pharmacist.
Patients should call their doctor for medical advice about any side effects. Patients or their caregivers may report side effects to the FDA at 1-800-FDA-1088. They may also report side effects to Genentech at 1-888-835-2555.
Patients should read the Zelboraf full Prescribing Information and Medication Guide for additional important safety information at http://www.zelboraf.com.
About Metastatic Melanoma and BRAF
When melanoma is diagnosed early, it is generally a curable disease. However, when it spreads to other parts of the body, it is the deadliest and most aggressive form of skin cancer. A person with metastatic melanoma typically has on average a short life expectancy that is measured in months. The American Cancer Society estimates there will be more than 70,000 new cases of melanoma and nearly 8,800 melanoma deaths this year in the United States.
The BRAF protein is a key component of the RAS-RAF pathway involved in normal cell growth and survival. Mutations that keep the BRAF protein in an active state may cause excessive signaling in the pathway, leading to uncontrolled cell growth and survival. These mutations of the BRAF protein are thought to occur in an estimated half of all melanomas and eight percent of solid tumors.
About BRAF V600 Mutation Testing
The cobas 4800 BRAF V600 Mutation Test is a polymerase chain reaction-based diagnostic test developed by Roche. This FDA-approved test was clinically validated in the BRIM2 and BRIM3 studies to identify tumors that carry the BRAF V600E mutation. The test has several advantages compared to Sanger sequencing, a commonly used method, including greater sensitivity and reliability for detecting mutations and quicker results, allowing doctors to know whether a person with inoperable or metastatic melanoma is eligible for treatment with Zelboraf.
About Zelboraf (pronounced ZEL-bor-af); vemurafenib (pronounced vem-yoo-RAF-en-ib)
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. Genentech and Daiichi Sankyo, Inc. will co-promote Zelboraf in the United States.
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 http://www.roche-trials.com (in the EU) or http://www.clinicaltrials.gov (in the United States).
About Genentech Access Solutions
Genentech is committed to people having access to our medicines. Genentech Access Solutions is a team of 450 Genentech employees who help those who need Genentech medicines. This team works with patients and doctors to resolve reimbursement and insurance issues and provides assistance to eligible patients in the United States who do not have insurance coverage or who cannot afford their out-of-pocket co-pay costs. For additional information, please visit http://www.GenentechAccessSolutions.com.
Founded more than 30 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious or life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.