Genentech Reports Positive Progression-Free Survival Results For Avastin In Brain Cancer Trial

Interim results of a Phase II study showed that 51 percent of patients receiving Avastin plus chemotherapy experienced six months of PFS, and 36 percent of patients taking Avastin alone had six-month PFS.

Avastin (bevacizumab) administered in combination with irinotecan improved six-month progression-free survival in patients with relapsed glioblastoma multiforme, with 51 percent of patients experiencing six months of PFS, interim data from a Phase II clinical study show.

The data also demonstrated that 36 percent of patients treated with Avastin alone lived without the disease advancing at six months, Genentech said Nov. 18.

The study is the first in relapsed GBM to show activity, the firm told "The Pink Sheet" DAILY, adding there is no treatment currently approved by FDA for that population.

Genentech reported results of the ongoing Phase II trial during the Annual Scientific Meeting of the Society for Neuro-Oncology in Dallas. A full analysis of the data will be available in 2008.

The results are significant, Genentech emphasized, because according to the American Cancer Society, the five-year survival rate GBM patients is three percent, a number that has not improved in more than 25 years.

If approved for the indication, Avastin would be the second GBM treatment on the market. Schering-Plough's Temodar (temozolomide) was cleared as first-line treatment for patients with newly diagnosed glioblastoma multiforme in 2004.

Genentech said it is in discussions with FDA regarding next steps for Avastin in relapsed GBM. The company also is deciding whether to initiate a Phase III first-line study in conjunction with the National Cancer Institute.

The Phase II, open-label, multi-center, randomized, non-comparative study enrolled 167 patients with GBM whose cancer had relapsed after first- or second-line therapy and who had received prior temozolomide.

Patients were randomized to receive Avastin alone or in combination with irinotecan every other week for up to 104 weeks.

The primary endpoints of the study were six-month PFS and objective response rate as determined by an independent radiology facility.

"Preliminary estimates of tumor response were observed in 21 percent (18/85) of patients treated with Avastin alone and in 34 percent (28/82) of patients treated with Avastin in combination with chemotherapy," Genentech said.

Secondary endpoints included overall survival and safety.

Adverse events seen in the trial were similar to those associated with Avastin in other studies, the firm noted. The most common severe toxicities in the Avastin alone arm were hypertension (8 percent) and convulsion (6 percent).

The most common severe adverse events in the Avastin plus chemotherapy arm were convulsion (13 percent) and neutropenia (9 percent).

There were two deaths associated with adverse events in the Avastin alone arm and one death associated with an adverse event in the Avastin plus chemotherapy arm.

The results were met with enthusiasm by Wall Street. If Avastin plus chemotherapy "can duplicate or modestly improve upon Temodar's efficacy, it stands an excellent chance of garnering a sizable share of the relapse market," Rodman & Renshaw analyst Michael King said in a Nov. 19 note.

Genentech could gain an orphan drug indication and file for an accelerated approval for Avastin in GBM, King added.

"We expect the target population for Avastin to exceed 7,000 patients. At current annual costs, this could amount to an incremental $350 million in sales."

Genmab plans to begin clinical trials of HuMax-Inflam , an antibody targeted to interleukin-8, in GBM in 2008 (¹ (Also see "Genmab To Initiate HuMax-Inflam Glioblastoma Trial In 2008" - Pink Sheet, 13 Sep, 2007.)).

Neopharm was dealt a setback with its GBM treatment besudotox (IL13-PE38QQR) earlier this year when FDA said the firm would be required to conduct an additional Phase III trial before it would accept the drug for submission (² (Also see "Neopharm Glioblastoma Drug Will Require Another Phase III Study, FDA Says" - Pink Sheet, 30 Mar, 2007.)).

-Brooke McManus ([email protected])