The applicant company Roche Registration Ltd. submitted to the European Medicines Agency (EMA) an application for marketing authorisation for
vemurafenib.
Vemurafenib is a low molecular weight, orally available, inhibitor of oncogenic V600 BRAF
serine-threonine kinase. Mutations in the BRAF gene which substitute the
valine at
amino acid position 600 constitutively activate BRAF
proteins, which will drive cell proliferation in the absence of
growth factors. Results from a phase 3 trial (N=675) comparing
vemurafenib 960 mg twice daily (taken either with or without food) to standard treatment
dacarbazine (
DTIC) in patients with BRAF V600E mutation-positive unresectable or metastatic
melanoma were submitted. The study met its primary efficacy objective after an interim analysis of overall survival. Patients were allowed to cross-over to the experimental arm following disclosure of the study results after the first interim analysis. In the update of the analysis, the median overall survival (OS) was 9.9 months versus 13.2 months for
DTIC and
vemurafenib, respectively (HR=0.67; 95% confidence interval (CI): 0.54, 0.84; cut-off 3 October 2011). Based on the updated analysis, the CHMP concluded that a survival benefit over
DTIC had been convincingly demonstrated, in the overall population. The follow-up was considered sufficiently mature with close to 50% of the events observed. The most common side effects (affecting more than 30% of patients) in
vemurafenib treated patients included
arthralgia,
fatigue,
rash, photosensitivity reaction,
nausea,
alopecia and
pruritus. Some patients treated with
vemurafenib developed cutaneous
squamous cell carcinoma which was readily treated by local surgery. The objective of this paper is to summarise the scientific review of the application leading to regulatory approval in the European Union (EU). The full scientific assessment report and product information, including the Summary of Product Characteristics (SmPC), are available on the EMA website (www.ema.europa.eu).