August 17, 2011
Plexxikon Announces FDA Approval of Zelboraf (vemurafenib) and Companion Diagnostic for the Treatment of Patients with BRAF Mutation-Positive Metastatic Melanoma
--Zelboraf Improves Survival in Patients With BRAFV600E Mutation-Positive Metastatic Melanoma, a Deadly Form of Skin Cancer--
Plexxikon Inc., a member of the Daiichi Sankyo Group, today announced that the U.S. Food and Drug Administration (FDA) has approved ZelborafTM (vemurafenib), for the treatment of patients with BRAFV600E mutation-positive inoperable or metastatic melanoma as detected by an FDA-approved test. Zelboraf is an oral drug that selectively targets this BRAF mutation that is present in about half of all cases of melanoma. Zelboraf was formerly known as PLX4032. The cobas 4800 BRAF V600 Mutation Test, a companion diagnostic which determines a patient’s eligibility for Zelboraf treatment if the tumor tests positive for the BRAFV600E mutation, also was approved by the FDA.
Daiichi Sankyo, Inc. and Genentech, a member of the Roche Group, will co-promote Zelboraf in the United States. The companies expect Zelboraf to be available in the marketplace in August 2011.
“As the first personalized medicine approved for the treatment of patients with BRAFV600E mutation-positive melanoma, Zelboraf represents a significant new treatment option for these patients suffering from inoperable or metastatic melanoma. We are grateful for the clinical trial participants, clinical investigators, collaborators and dedicated employees, who have all contributed to this important advancement in cancer treatment,” stated K. Peter Hirth, Ph.D., chief executive officer of Plexxikon. “Additionally, another benefit of a personalized medicine like Zelboraf has been the ability to accelerate development, enabling Plexxikon and its collaborators to bring this drug to market in less than six years from our discovery of the molecule in 2005. With that same focus and commitment, Plexxikon looks forward to advancing our pipeline of diverse product candidates and pursuing the discovery and development of other novel agents.”
Zelboraf Efficacy in BRAFV600E Mutation-Positive Metastatic Melanoma
The FDA approval follows positive results of an interim analysis in January 2011 of BRIM3, a Phase 3 clinical study initiated in December 2009.
BRIM3 is a global, randomized, open-label, controlled, multicenter, Phase 3 study that compared Zelboraf to dacarbazine chemotherapy, in 675 patients with previously untreated BRAFV600E mutation-positive, unresectable (inoperable) or metastatic melanoma. The BRIM3 study met the pre-specified criteria for co-primary endpoints of overall survival (OS) and progression-free survival (PFS) in January 2011. Results were reported in June 2011 at the American Society of Clinical Oncology Annual Meeting and simultaneously published in the June 2011 issue of the New England Journal of Medicine. An updated analysis of the data as of March 31, 2011 showed:
â—¦In BRIM3, the risk of death was reduced by 56 percent for patients who received Zelboraf compared to those who received chemotherapy (hazard ratio [HR]=0.44, p<0.0001).
â—¦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
â—¦Patients 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.
â—¦The confirmed investigator-assessed response rate (those who experienced ≥30 percent tumor shrinkage) in patients 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).
A Phase 2 study, BRIM2, initiated in September 2009, enrolled 132 previously treated patients with metastatic melanoma with the BRAF mutation. The primary endpoint was confirmed overall response rate as assessed by independent review. Results included:
â—¦In BRIM2, Zelboraf shrank tumors thirty percent or greater in 52 percent of patients.
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 protects 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 are encouraged to report negative side effects of prescription drugs to the FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch. They may also report side effects to Genentech at 1-800-835-2555.
Patients should read the Zelboraf full Prescribing Information and Medication Guide for additional important safety information at www.zelboraf.com.
About Zelboraf (vemurafenib / PLX4032)
Zelboraf is an oral, small molecule, kinase inhibitor indicated for the treatment of patients with unresectable or metastatic melanoma with BRAFV600E mutation as detected by an FDA-approved test. Zelboraf is not recommended for use in melanoma patients who lack the BRAFV600E mutation.
Plexxikon utilized its structure-guided chemistry platform to discover Zelboraf, and initiated clinical development in 2006. Plexxikon and Roche signed a license and collaboration agreement in 2006 to co-develop Zelboraf. Under a 2005 agreement, a DNA-based companion diagnostic to identify patients whose tumors carry the BRAFV600E mutation was co-developed by Roche Molecular Systems and Plexxikon in parallel with the therapeutic development of Zelboraf. In May 2011, Plexxikon also announced that a separate application for market approval of Zelboraf was submitted to the European Marketing Agency (EMA) in addition to the market approval application in the U.S.
Studies of Zelboraf in combination with other approved and investigational medicines as well as in other tumor types are being conducted by Roche, Plexxikon and Genentech. More information about ongoing Zelboraf studies is available at www.clinicaltrials.gov (in the U.S.) or www.clinicaltrialsregister.eu or on the Roche Clinical Trials Registry at www.roche-trials.com (in the EU). Genentech can also be contacted by calling the company’s clinical trial call center at 888-662-6728 or emailing firstname.lastname@example.org.
About Melanoma and BRAF mutation
Melanoma is the most serious type of skin cancer and is growing at a rate of about five to six percent annually. More than 70,000 people in the U.S. and 160,000 people worldwide are diagnosed with melanoma each year. It is one of the deadliest cancers, with a five-year survival rate of 15 percent for people with advanced (Stage IV) melanoma, according to the American Cancer Society.
Risk factors for melanoma include a positive family history of melanoma, prior melanoma, multiple clinically atypical moles or dysplastic nevi, inherited genetic mutations, fair skin and sun exposure. However, melanoma can occur in any ethnic group and also in areas of the body without substantial exposure to the sun.
The BRAF gene is a key component of a pathway involved in normal cell growth and survival. BRAF mutations may lead to uncontrolled cell growth, and are thought to occur in about half of all cases of melanoma and eight percent of all solid tumors.
Plexxikon, a member of the Daiichi Sankyo Group, is a leader in the structure-guided discovery and development of novel small molecule pharmaceuticals to treat human disease. The company’s lead drug Zelboraf (vemurafenib/PLX4032) was approved by the FDA in August 2011, and will be co-promoted in the U.S. by Daiichi Sankyo, Inc. and Genentech. PLX3397, the company’s next oncology candidate, has advanced to Phase 2 testing in 2011. The company is developing a portfolio of clinical and preclinical stage compounds to address significant unmet medical needs in oncology, as well as in several other therapeutic indications. Plexxikon’s proprietary Scaffold-Based Drug Discovery™ platform integrates multiple state-of-the-art technologies, including structural screening as a key component that provides a significant competitive advantage over other drug discovery approaches.