The halt of a phase III trial of Cell Genesys’ therapeutic cancer vaccine GVAX immunotherapy, after more deaths were reported in the treatment arm, is not only a body blow to the company, but is also a kick in the teeth to an area of research which has continued to disappoint this year.
While it is not quite over yet for GVAX, which was partnered with Takeda in April, the 72% plunge in the US company’s shares yesterday indicates hopes are not high. Until further analysis of the trial in question becomes available in a couple of months, and a futility analysis is conducted on a second more advanced phase III study, which will take about one month, the stock has no chance of recovering.
Cell Genesys announced yesterday that the trial Vital-2 was stopped after its Independent Data Monitoring Committee (IDMC) found that 67 deaths had occurred in the treatment arm, versus 47 in the control arm. A total of 408 patients had been enrolled so far out of the 600 planned.
The study was pitting GVAX immunotherapy in combination with Taxotere against Taxotere in combination with prednisone, in patients with symptomatic metastatic hormone refractory prostate cancer. The treatment period was six months, and on a conference call Cell Genesys management said they did not know how many patients had completed the course to date.
The company declined to speculate on what caused the imbalance of deaths without looking into the cases in more detail. It added that it does not know yet whether enough patients had received the full six months of treatment to allow a meaningful analysis of any data salvaged.
No safety issues
On the plus side, no new safety issues have emerged. More deaths were always more likely in this trial than in Vital-1, as the population is much sicker. Vital-1 is in patients with hormone refractory metastatic prostate cancer, who have failed radiotherapy and hormone therapy, have evidence of cancer in the skeleton but have not yet developed any symptoms.
Hence Vital-1 pits GVAX as a monotherapy against Taxotere combined with prednisone, and is the same design as successful phase II trials. In Vital-2, the patients are symptomatic and all have started receiving the chemotherapy Taxotere, a patient population not previously tested.
The futility analysis which the IDMC is about to undertake will indicate whether similar problems lay ahead for Vital-1, although an interim analysis conducted in January concluded that the trial should continue. All patients have completed dosing, so a full read out is possible, due next year.
Will cancer vaccines ever work?
While some may cling on to hope that the Vital-1 trials might still yield positive results, the track record of therapeutic cancer vaccines does not instil great confidence.
The failure of Favrille’s SpecifId in May and Genitope’s MyVax in December, disappointing results from Oxford BioMedica’s TroVax last month and Dendreon’s ongoing struggles with Provenge has not been encouraging. Experts believe that while the theory behind the approach, harnessing the immune system to fight cancer, is sound, the ability to turn that into clinically meaningful results is not quite there yet.
Another big event for the field, an interim analysis of Dendreon’s phase III trial of Provenge, is due in October. With further details on GVAX likely to emerge over the next few months, researchers will soon be able to gain a better idea of how much actual progress has been made with cancer vaccines over the last few years.