GVAX: development halted

Cell Genesys has decided to terminate the Phase III VITAL-1 (Vaccine ImmunoTherapy with Allogeneic Prostate Cancer Cell Lines) trial of GVAX immunotherapy in patients with asymptomatic, metastatic hormone-refractory prostate cancer (HRPCA) following an independent Data Monitoring Committee (IDMC) analysis, which indicated that the trial had a <30 per cent chance of meeting its predefined primary endpoint of an improvement in survival. In August, the company halted VITAL-2, the second Phase III trial investigating GVAX in PCA, after a recommendation from the IDMC following the observation of an imbalance in deaths between the two treatment arms.

Following the termination of VITAL-2, Cell Genesys requested the IDMC conduct a futility analysis of the VITAL-1 trial, which was fully enrolled in 2007 with 626 patients and compared GVAX to Taxotere (docetaxel) plus prednisone. The latest news hit the company's stock price hard, with shares falling by 73 per cent from a close of US$0.61 on 15th October to open at US$0.16 on 16th October.

In view of these terminations, Cell Genesys is to place on hold the further development of GVAX for PCA pending a review of the programme with its collaborator, Takeda Pharmaceutical. As a result, Cell Genesys will reduce its staff of 290 by approximately 75 per cent by the end of 2008, with further reductions anticipated in the first half of 2009 as additional activities are phased out. As of 30th September, the company had approximately US$150 million in cash and currently estimates that the year-end cash will be approximately US$128 million. Personnel-related restructuring charges of approximately US$12.8 million are expected to be incurred in the fourth quarter of 2008.

Cell Genesys has also reported results of a preliminary analysis of the VITAL-2 trial. In contrast to VITAL-1, the VITAL-2 study was conducted in patients with symptomatic, metastatic HRPCA and compared the combination of GVAX+docetaxel to docetaxel+prednisone as a control. At the time that this study was terminated, the IDMC reported an imbalance in deaths between the two treatment arms that was observed during a routine safety monitoring meeting of the committee. More specifically, of 114 deaths at the time of the IDMC review, 67 occurred in the GVAX+docetaxel treatment arm and 47 in the docetaxel+prednisone control arm.

A total of 408 patients had been enrolled in the study up to that point in time. The company has now conducted an initial analysis of the incomplete trial data set that was reviewed by the IDMC in August. The analysis has revealed no apparent imbalance in patient baseline characteristics with respect to both demographic and disease prognostic factors. In addition, no significant toxicities in the GVAX+docetaxel therapy arm were observed that could explain the imbalance in deaths and in fact, the vast majority of deaths in both treatment arms were reported as due to progression of PCA. Of note, fewer treatment cycles with docetaxel were administered to patients in the GVAX+docetaxel arm compared to the control arm, a difference which was statistically significant.

In a conference call, the company's Chief Executive Officer, Stephen Sherwin, stated that Cell Genesys has since found no evidence that the GVAX regimen carried toxic effects that could explain the additional deaths. "We don't have all the answers," he commented, although cancer sufferers, shareholders and employees will wish that he at least had some.

Matthew Dennis - Editor, Cancer Drug News