New Drug Applications Submitted for Vemurafenib Market Approval in Melanoma

BERKELEY, Calif.--()--Plexxikon Inc., a member of the Daiichi Sankyo Group, today announced that applications for market approval for vemurafenib (PLX4032/RG7204) for the treatment of metastatic melanoma have been submitted to the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Additionally, a pre-marketing application for approval for a companion diagnostic test has been submitted in the U.S.; the test also will be registered in Europe. Vemurafenib is an oral drug that selectively targets the BRAF V600 mutation, which occurs in about half of all cases of melanoma and eight percent of all solid tumors. The companion diagnostic determines whether a patient’s tumor tests positive for the BRAF mutation and is eligible to receive vemurafenib treatment.

“We are truly excited to have reached this milestone for vemurafenib, particularly for the melanoma patients who are in desperate need of new treatment options,” said K. Peter Hirth, Ph.D., chief executive officer of Plexxikon. “From the discovery of vemurafenib in 2005 to this submittal for marketing approval, a dedicated team has advanced this personalized medicine through development as expeditiously as possible for the benefit of patients. Our partner, Roche, as well as our clinical investigator team and collaborators, have collectively made this a truly rewarding collaboration.”

The submissions are based on results from Phase 2 and 3 trials (BRIM2 and BRIM3) that evaluated vemurafenib in patients with BRAF V600 mutation-positive melanoma, as determined by the cobas 4800 BRAF V600 Mutation Test. Earlier this year, the company reported positive data from an interim analysis of BRIM3 which showed that the study met the pre-specified criteria for co-primary endpoints for BRIM3 for progression-free survival and overall survival, and that the safety profile was generally consistent with the previous vemurafenib studies. Based on these results, the data safety monitoring board for the trial recommended early termination of the trial and allowed dacarbazine-treated patients to immediately cross over to vemurafenib treatment. BRIM2 results reported earlier showed a 52 percent confirmed response rate, with tumor shrinkage in the majority of patients, consistent with results from earlier studies.

The most frequent Grade 3 adverse event observed in clinical trials of vemurafenib was cutaneous squamous cell carcinoma, a common skin cancer treated by local excision (minor surgery done in a physician’s office). The most common adverse events were rash, increased sun sensitivity, joint pain, hair loss and fatigue. Possible serious side effects of vemurafenib include liver problems, changes in heartbeat or very fast or abnormal heartbeats, and allergic reactions.

Comprehensive data from BRIM3 will be presented at a plenary session at the 47th Annual Meeting of the American Society of Clinical Oncology (ASCO) in June. Updated BRIM2 data also will be presented at ASCO.

Current studies of vemurafenib are being conducted by Roche, Plexxikon’s co-development partner under a 2006 collaboration agreement, and Genentech, Roche's U.S. oncology unit. Roche has submitted applications with the health authorities for market approval for both vemurafenib and the companion diagnostic. Additional clinical trials are planned, including combinations with other approved drugs and investigational agents, as well as in other cancers. During the marketing application review period, vemurafenib is available to eligible patients with BRAF V600 mutation-positive melanoma through a global patient access program. More information about this program or other vemurafenib 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 contracted by calling the company’s clinical trial call center at 888-662-6728 or emailing genentechclinicaltrials@druginfo.com.

About Melanoma

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.

About Vemurafenib (PLX4032)—A Personalized Medicine for Cancer Treatment

Vemurafenib is a novel, oral small molecule for treating melanoma and other cancers harboring the oncogenic BRAF mutation. Plexxikon utilized its structure-guided chemistry platform to discover vemurafenib, and initiated clinical development in 2006. Plexxikon and Roche signed a license and collaboration agreement in 2006 to co-develop vemurafenib. Under a 2005 agreement, a DNA-based companion diagnostic to identify patients whose tumors carry the BRAF mutation is being co-developed by Roche Molecular Systems and Plexxikon in parallel with the therapeutic development of vemurafenib.

About Plexxikon

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 compound, vemurafenib (PLX4032), is in late-stage clinical trials for the treatment of melanoma, and the subject of recent applications for marketing approval in the U.S. and Europe. 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.

In April 2011, Daiichi Sankyo acquired Plexxikon. Plexxikon continues research and development operations as an independent unit of and member of the Daiichi Sankyo Group. Under Plexxikon’s U.S. co-promotion agreement with Genentech signed in 2010, Daiichi Sankyo, Inc. will co-promote vemurafenib, subject to market approval by FDA. For more information, please visit www.plexxikon.com.

Contacts

Plexxikon Inc.
Kathleen Sereda Glaub, +1-510-647-4009
President
kglaub@plexxikon.com
or
For Plexxikon
Susan Kinkead, +1-415-751-3611
susan@kinkeadcomm.com
or
Jennifer Cook Williams, +1-360-668-3701
jennifer@cwcomm.org

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Contacts

Plexxikon Inc.
Kathleen Sereda Glaub, +1-510-647-4009
President
kglaub@plexxikon.com
or
For Plexxikon
Susan Kinkead, +1-415-751-3611
susan@kinkeadcomm.com
or
Jennifer Cook Williams, +1-360-668-3701
jennifer@cwcomm.org