Positive results from Plexxikon's vemurafenib Phase 2 and 3 trial against metastatic melanoma

Plexxikon Inc., a member of the Daiichi Sankyo Group, today announced efficacy and safety data from the BRIM3 trial, a large, randomized, multi-center Phase 3 clinical study of vemurafenib in patients with previously untreated metastatic melanoma with the BRAF^V600 mutation. The BRIM3 study met the pre-specified criteria for co-primary endpoints of overall survival (OS) and progression-free survival (PFS). For patients treated with vemurafenib compared to those treated with chemotherapy, the risk of death was significantly reduced, by 63 percent, as reflected by the hazard ratio of 0.37, and a p value of less than 0.0001. In addition, vemurafenib treatment significantly reduced the risk of disease progression, by 74 percent.

BRIM3 data also will be presented today by Paul Chapman, M.D., a medical oncologist and attending physician in the Melanoma and Sarcoma Service at Memorial Sloan Kettering Cancer Center and principal investigator of BRIM3, in a plenary session at the 2011 Annual Meeting of the American Society for Clinical Oncology (ASCO) meeting in Chicago (Abstract #LBA4, June 5, 2011 3:15 - 3:30 pm CDT, Hall B1).

Key data from the 675-patient BRIM3 trial, based on the analysis as of December 30, 2010, showed:

• Six months after randomization to treatment, 84 percent of vemurafenib-treated patients were alive, compared to 64 percent of patients randomized to chemotherapy.
• More patients treated with vemurafenib experienced tumor shrinkage (48.4 percent) than patients treated with chemotherapy (5.5 percent).
• Median OS could not be reliably estimated at the time of this analysis since the median time for patients receiving treatment was only 3.75 months (median follow up). However, at that time, the estimated median OS in the vemurafenib treatment arm was 9.23 months compared to 7.75 months in the chemotherapy arm. As of an updated analysis on March 1, 2011, the estimated median OS was 10.51 months for the vemurafenib treatment arm, while the chemotherapy arm remained unchanged at 7.75 months.
• Median progression-free survival (PFS) was 5.3 months compared to 1.6 months in the chemotherapy arm.
• All subgroups of patients in the vemurafenib arm showed consistent benefit in terms of OS, PFS and tumor shrinkage, regardless of disease staging, age, gender or performance status.

In January 2011, the data safety monitoring board for BRIM3 recommended termination of the study due to compelling efficacy data, and further recommended that study patients receiving chemotherapy have the option to crossover to the vemurafenib treatment arm.

Updated results from BRIM2 as of January 31, 2011, also were presented at ASCO by Antoni Ribas, M.D., a medical oncologist, UCLA Jonsson Comprehensive Cancer Center. BRIM2 met its primary endpoint, and these data were consistent with earlier BRIM2 data reported at the Society for Melanoma Research in November 2010. This study enrolled 132 previously treated melanoma patients with the BRAF^V600 mutation, and updated results showed:

• Tumor shrinkage with a confirmed response rate of 53 percent.
• 29 percent of patients showed stable disease.
• Median progression-free survival was 6.7 months.
• Median duration of response also was 6.7 months.
• Median OS had not been reached; however, at 12 months, 58 percent of patients treated with vemurafenib were alive. Median follow up was 10 months.

The safety profile demonstrated in both BRIM3 and BRIM2 trials was consistent with previous vemurafenib data. The most frequent Grade 3 adverse event observed in these studies was cutaneous squamous cell carcinoma, a common skin cancer treated by local excision (minor surgery done in a physician's office), with continuation of treatment. The most common adverse events were rash, increased sun sensitivity, joint pain, hair loss and fatigue. Adverse events also were generally reversible with dose modification or interruption. Possible serious side effects of vemurafenib include liver problems, changes in heartbeat or very fast or abnormal heartbeats and allergic reactions.

"We are very enthusiastic about the potential benefits seen with vemurafenib treatment in BRAF mutation-positive melanoma patients," said K. Peter Hirth, chief executive officer of Plexxikon. "The consistency and statistical significance of the data generated to date from BRIM3, BRIM2 and even seen early on in the Phase 1 trial, underscores the power of a personalized medicine approach for patients. Not only have we been able to detect an efficacy signal early on in the clinic, but we have been able to accelerate development of this molecularly targeted treatment, in combination with a companion diagnostic, ultimately for the benefit of patients."

"The data presented from studies conducted with vemurafenib treatment provide new hope to patients who currently have limited treatment options. We remain committed to bringing innovative solutions, like vemurafenib, to patients by combining potent therapies with diagnostic tools to provide better outcomes," said Glenn Gormley, chief science officer, Daiichi Sankyo.