Congratulations to researchers from Plexxikon (now Daiichi Sankyo) and Genentech on the FDA Approval of Zelboraf – an oral, small molecule kinase inhibitor for skin cancer!
For all the bad news we read, it is important as a community that we celebrate our scientific and business triumphs.
Here are the exciting results of the phase 3 trial and technical description from Plexxikon’s announcement (you can read the full release here):
- In BRIM3, the risk of death was reduced by 56 percent for patients who received Zelboraf compared to those who received chemotherapy (hazard ratio [HR]=0.44, p<0.0001).
- At the time of analysis, median overall survival of patients receiving Zelboraf had not been reached, and was 7.9 months for those receiving chemotherapy
- Patients who received Zelboraf also had a 74 percent reduced risk of the disease getting worse or dying (PFS) compared to those who received chemotherapy (HR=0.26, p<0.0001). Median PFS was 5.3 months for those who received Zelboraf compared to 1.6 months for those who received chemotherapy.
- The confirmed investigator-assessed response rate (those who experienced ≥30 percent tumor shrinkage) in patients who received Zelboraf was 48.4 percent (1 percent complete responses and 47.4 percent partial responses) compared to 5.5 percent (partial responses) for those who received chemotherapy (p<0.0001).
Zelboraf is an oral, small molecule, kinase inhibitor indicated for the treatment of patients with unresectable or metastatic melanoma with BRAFV600E mutation as detected by an FDA-approved test. Zelboraf is not recommended for use in melanoma patients who lack the BRAFV600E mutation.
Plexxikon utilized its structure-guided chemistry platform to discover Zelboraf, and initiated clinical development in 2006.
Genentech’s website goes into a bit more detail on the PCR-based diagnostic test targeting the drug to patients with the appropriate mutation in their release explaining:
The FDA today also approved the cobas 4800 BRAF V600 Mutation Test, a diagnostic test developed by Roche to identify patients eligible for treatment. Zelboraf is the first and only FDA-approved personalized medicine shown to improve survival in people with BRAF V600E mutation-positive metastatic melanoma, demonstrating the benefits of Roche’s personalized healthcare approach. It is designed to target and inhibit some mutated forms of the BRAF protein found in about half of all cases of melanoma, the deadliest and most aggressive form of skin cancer.
The NY Times earlier ran a piece questioning if it was ethical to withhold treatment for half the patients with a life threatening cancer, when those receiving the drug were responding so significantly better in the clinical trials.
It is an inspiring story, where the FDA even approved the drug a bit earlier than is typical in the process. Peter Hirth and collaborators are getting a well deserved reputation for knowing how to successfully screen kinases for small molecule drugs (first at Sugen and now with Plexxikon). As usual, Luke Timmerman has the inside story in Xconomy hinting at future developments here.
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