ZELBORAF™ is a kinase inhibitor indicated for the treatment of patients with unresectable or metastatic melanoma with BRAFV600E mutation as detected by an FDA-approved test. (1, 5.10)
Limitation of Use: ZELBORAF is not recommended for use in patients with wild-type BRAF melanoma. (5.10, 14).
The cobas® 4800 BRAF V600 Mutation Test is an in vitro diagnostic device intended for the qualitative detection of the BRAF V600E mutation in DNA extracted from formalin-fixed, paraffin-embedded human melanoma tissue. The cobas® 4800 BRAF V600 Mutation Test is a real-time PCR test on the cobas 4800 system, and is intended to be used as an aid in selecting melanoma patients whose tumors carry the BRAF V600E mutation for treatment with vemurafenib.
Both drug and test were developed by Roche using their two health care arms in therapeutics and diagnostics. For the first time, the drug label indicated a testing requirement.
As was the case with Herceptin/HercepTest, both Zelboraf and BRAF were approved on the same day.
In theory, targeted therapy clinical trials could be shorter and cheaper as the therapy would demonstrate a higher efficacy or safety profile in the stratified group.
In practice, delivering on this promise has been difficult due to regulatory requirements to include non-targeted populations in safety studies and late identification of biomarkers in the clinical program.
Clinical trial length, as well as approval time for Zelboraf after the application to the FDA, was significantly shorter than the average for comparable oncology therapies.
Several factors were involved in allowing this timeline.
Metastatic melanoma has a poor prognosis and is a difficult-to-treat condition. Given the few options for these patients, the FDA is more likely to grant a quick approval.
BRAF testing has been available for some time from a range of US laboratories due to applications in a number of oncology areas. One key aspect of the FDA premarket approval process is the quality of testing done in clinical practice (beyond the highly structured clinical trials). Due to the long use of BRAF testing in the US, the lab-to-lab variability of the testing was known.
Many Rx-Dx collaborations undervalue the Dx role.
Roche, however, may easily value the overall revenue potential of the targeted therapy. The earlier the partnership is established, the more experience in the clinical trials with the commercial test is gained, and this is experience the FDA values in its approval processes.
BRAF mutation testing required for the use of Zelboraf has been embraced by oncologists since its launch in 2011.
Although reimbursement issues have initially been challenging these are expected to be covered within the next 12 months [by 2013].