BERKELEY, Calif. & LOS ANGELES--(BUSINESS WIRE)--Plexxikon today announced that updated Phase 1 clinical data of Zelboraf® (vemurafenib) were presented at the Society for Melanoma Research (SMR) 2012 Congress, held November 8-11 in Los Angeles, CA. These data represent the longest follow-up of any cohort of patients treated with any BRAF inhibitor. The data show that 26 percent of patients were alive at three years suggesting that long-term survival with Zelboraf can be achieved in a subset of metastatic melanoma patients with the BRAF V600E mutation.
“Since initiating the first clinical trial in 2006, our primary goal has been to provide a new treatment option for metastatic melanoma patients with the BRAF V600E mutation who historically have had very limited treatment options.”
The Phase 1 extension study, which was conducted by Plexxikon and Plexxikon’s partner Roche, included 32 patients with BRAF V600E mutation-positive melanoma. As of July 17, 2012, the date of the analysis, the data showed:
• Long-term overall survival:
55% of patients were alive at 1 year
36% of patients were alive at 2 years
26% of patients were alive at 3 years
• Progression-free survival (PFS) benefit:
Median PFS of 7.7 months
Five patients remain on vemurafenib to date, three of whom continue to have complete responses with no evidence of disease and one of whom continues to have a partial response.
Data also suggest a potential benefit of vemurafenib’s use in conjunction with post-progression surgery, as well as continued drug administration in some patients with isolated melanoma metastases. Fourteen of the 32 patients received vemurafenib post-progression.
The most common drug-related adverse events in this Phase 1 study were joint pain, rash, nausea, sun sensitivity, fatigue, cutaneous squamous cell carcinoma, itching and hand-foot syndrome.
“Plexxikon is pleased to report the results from this study, which demonstrate that long term survival was achieved in a subset of patients,” said K. Peter Hirth, Ph.D., chief executive officer of Plexxikon. “Since initiating the first clinical trial in 2006, our primary goal has been to provide a new treatment option for metastatic melanoma patients with the BRAF V600E mutation who historically have had very limited treatment options.”
Other Zelboraf Clinical Trial Results Continue to Mature
Zelboraf was approved by FDA in August 2011, following positive results of an interim analysis of BRIM3, a global, randomized, open-label, controlled Phase 3 study that compared Zelboraf to dacarbazine (chemotherapy), in 675 patients with previously untreated BRAF V600E mutation-positive, unresectable (inoperable) or metastatic melanoma. The BRIM3 study met the specified criteria for co-primary endpoints of overall survival and progression-free survival in January 2011. The risk of death was reduced by 56 percent for patients who received Zelboraf compared to those who received chemotherapy (hazard ration [HR]=0.44, p<0.0001). Median overall survival of patients receiving Zelboraf had not been reached, and was 7.9 months for those receiving chemotherapy. There were 78 deaths and 121 deaths in the Zelboraf and dacarbazine arms, respectively. Median PFS was 5.3 months for those who received Zelboraf compared to 1.6 months for those who received chemotherapy (HR=0.26, p<0.0001).
In June 2012, updated results from the BRIM3 study were reported at the 48th Annual American Society of Clinical Oncology (ASCO) Meeting. In an analysis of BRIM3 data with a longer follow-up compared to previous analyses, including crossover of patients from the chemotherapy treatment arm to the Zelboraf treatment arm, Zelboraf improved survival by providing a median overall survival of 13.6 months compared to 9.7 months in those who received chemotherapy. The risk of death in patients receiving Zelboraf was reduced by 30% compared to those receiving chemotherapy (HR=0.70, p<0.001). Until recently, patients with metastatic melanoma could only expect to live for six to nine months after diagnosis.
In February 2012, updated results from the BRIM2 trial, a single arm, multi-center Phase 2 clinical study of vemurafenib in patients with previously treated V600E BRAF mutation-positive metastatic melanoma, were published in the New England Journal of Medicine. The study demonstrated that patients who were treated with vemurafenib had a median overall survival of 15.9 months, compared with historical survival of nine months with conventional treatment. At 12 months, 58 percent of patients treated with vemurafenib were still alive.
About Zelboraf (vemurafenib)
Vemurafenib is a novel, oral small molecule, which was approved by the FDA in 2011 and is being marketed in the U.S. as Zelboraf for the treatment of patients with BRAF V600E mutation-positive inoperable or metastatic melanoma as detected by an FDA-approved test. Zelboraf is not recommended for use in melanoma patients who lack the BRAF V600E mutation.
Plexxikon utilized its structure-guided chemistry platform to discover vemurafenib, and initiated clinical development in 2006. Zelboraf was co-developed under a 2006 license and collaboration agreement between Roche and Plexxikon.
The cobas 4800 BRAF V600 Mutation Test, a DNA-based companion diagnostic used to identify patients whose tumors carry the BRAF mutation, was simultaneously approved in the U.S., and is CE marked and commercially available in Europe. Roche Molecular Diagnostics developed the cobas 4800 BRAF V600 Mutation Test following a 2005 agreement with Plexxikon.
Zelboraf has been used to treat 11,000 patients worldwide and is approved by 43 countries globally to date.
Plexxikon 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 2011, and is being co-promoted in the U.S. by Daiichi Sankyo Inc. and Genentech. 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 Scaffold-Based Drug DiscoveryTM 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. Plexxikon has been a member of Daiichi Sankyo Group since April 2011.
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 sore or 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 are encouraged to report side effects to Genentech and the FDA. They may contact Genentech by calling 1-888-835-2555. They may contact the FDA by visiting www.fda.gov/medwatch or calling 1-800-FDA-1088.
Patients should read the Zelboraf full Prescribing Information and Medication Guide for additional important safety information at http://www.zelboraf.com