Companion Diagnostic Accelerates Drug To Market

Vemurafenib (Zelboraf) is an oral B-Raf kinase inhibitor originally co-developed by Plexxikon (now part of Daiichi-Sankyo) and Genentech (member of the Roche group or whatever the correct term is) in 2006 for the treatment of late-stage unresectable or metastatic melanoma with the BRAF V600E mutation. It is estimated that 50-60% of melanomas harbor this mutation at amino acid position 600, where valine is replaced by glutamic acid. Vemurafenib is only effective against tumors that harbor the BRAF V600E mutation.

In 2006, Plexxikon entered into a collaboration agreement with Roche Molecular Diagnostics to develop a companion diagnostic test on the Cobas platform to screen for the presence/absence of the BRAF V600E mutation. Initial Phase I studies showed that 80% of patients with a V600E mutation in BRAF showed partial to complete regression.

Phase II (BRIM2) and Phase III (BRIM3) studies were initiated in 2009. Positive results from the phase III trial were reported in 2011, where the response rate was 48.4% among vemuranfenib patients compared to 5.5% of chemotherapy-treated patients. Median progression-free survival for vemuranfenib patients was 5.3 months compared to 1.6 months.

In April 2011, both the companion diagnostic test as well as the drug, branded as Zelboraf, was submitted to the FDA for approval. In August 2011, less than 4 months after submission and just 5 years after the initial IND filing, Vemurafenib received FDA approval for both the drug and its companion diagnostic test.

"Zelboraf provides an excellent example of how a coordinated drug and companion diagnostic development approach can accelerate the FDA approval process," states Dr. Phil Cotter, Principal and Co-Founder of ResearchDx, and the Laboratory Director of Pacific Diagnostics Clinical Laboratory in Irvine, CA.

For more information, visit www.researchdx.com.