On April 9, 2014 Chugai Pharmaceutical reported that it has filed a new drug application to the Ministry of Health, Labour and Welfare (MHLW) on April 9, 2014, for oral, selective BRAF kinase inhibitor vemurafenib (Development code: RG7204) for the treatment of melanoma with BRAFV600 mutation (Press release Chugai, APR 9, 2014, View Source [SID:1234500389]).
Also, Roche Diagnostics has filed a new drug application to MHLW for in vitro diagnostics to detect the BRAF mutation cobas 4800 BRAF V600 Mutation Test, as a companion diagnostics for vemurafenib on March 14, 2014. Roche Diagnostics is aimed at simultaneous approval of vemurafenib.
Chugai filed the application with the MHLW based on the results from the global phase III clinical trial (NO25026, The BRIM3 study) and the Japanese phase I/II clinical trial (The JO28178 study).
The BRIM3 study compared vemurafenib to dacarbazine, a standard of care, in 675 patients with previously chemotherapy naïve metastatic melanoma with BRAFV600 mutation, diagnosis by cobas 4800 BRAF V600 Mutation Test. As a result, the risk of death was reduced by 63 percent for people who received vemurafenib compared to those who received dacarbazine (hazard ratio=0.37, p<0.001). Patients who received vemurafenib had a 74 percent reduced risk of the disease getting worse or dying (progression free survival: PFS) compared to those who received dacarbazine (hazard ratio=0.26, p<0.001). Median PFS was 5.3 months for those who received vemurafenib compared to 1.6 months for those who received dacarbazine. The common adverse events in patients receiving vemurafenib were joint pain, rash, fatigue and skin tumor. The tolerability of vemurafenib was confirmed, based on the fact that for most adverse events, patients were able to continue the treatment with vemurafenib by receiving additional treatments for adverse events, or by temporarily halting the administration of vemurafenib or changing of the dose. The JO28178 study was conducted in two phases in 11 patients of Melanoma with BRAFV600 mutation, diagnosis by cobas 4800 BRAF V600 Mutation Test; the phase 1 portion was conducted to evaluate initial safety, and the phase 2 portion was conducted to evaluate the efficacy and safety. The result showed that the efficacy and the tolerability of vemurafenib in Japanese patients with melanoma are confirmed. cobas 4800 BRAF V600 Mutation Test is a genetic testing kit to detect the BRAFV600 mutation in genomic DNA extracted from melanoma tissue. It is the first diagnostic tool to detect the BRAF mutation using the measurement principle of real-time PCR method, for use prior to the administration of vemurafenib.