Genentech Seeks FDA Approval for Avastin in Glioblastoma

Genentech announced today that it has submitted a supplemental Biologics License Application (sBLA) to the FDA for the use of its anti-VEGF mAb, bevacizumab (Avastin), in recurrent glioblastoma multiforme (GBM). The application will be considered for accelerated approval, according to Genentech, if accepted by the FDA.

The sBLA is based on data from a recent phase 2 trial, in which bevacizumab (with or without randomized irinotecan chemotherapy) was administered to 167 patients with recurrent, treatment-refractory GBM. Primary endpoints of the study, assessed by MR imaging, were 6-month progression-free survival (PFS) and response rate (≥50% decrease in tumor size). Median durations of treatment were 16 weeks with bevacizumab alone and 22 weeks with bevacizumab plus irinotecan.

Efficacy and safety outcomes were presented, as follows, at the annual meeting of the American Society of Clinical Oncology (ASCO) in June of this year.*

The investigators also reported a substantial decline in the use of corticosteroids with either treatment.

Two hemorrhages (grade ≥3), one outside of the CNS, were reported with bevacizumab use. The rate of grade ≥3 infection with either treatment was approximately 10%.

The current standard of initial care for GBM is surgical debulking followed by radiation therapy and concurrent temozolomide (which is followed by maintenance temozolomide). There is no standard of care for recurrent disease. Reported response rates with single-agent irinotecan in the recurrent setting are 15% or less.

The rationale for using bevacizumab in GBM is based on the high rate of VEGF expression in the tumor. Genentech reports that it plans to initate a global phase 3 study of Avastin in newly diagnosed GBM next year. 

CNS = central nervous system; mAb = monoclonal antibody; MR = magnetic resonance; VEGF = vascular endothelial-cell growth factor.

* Cloughesy T et al. A phase II, randomized, non-comparative clinnical trial of the effect of bevacizumab (BV) alone or in combination with irinotecan (CPT) on 6-month progression free survival (PFS6) in recurrent, treatment-refractory glioblastoma (GBM).

HT to the WSJ Health Blog, which reports that the estimated cost for a course of bevacizumab treatment for GBM is nearly $40,000.