Staff Writer

In yet another setback for cancer vaccines, Cell Genesys Inc. terminated one of its two Phase III trials with prostate cancer vaccine GVAX.

The trial's independent data monitoring committee (IDMC) recommended the action after a routine safety review on Tuesday turned up an imbalance in deaths between the treatment and control arms of the study. Specifically, 114 out of 408 patients in the trial died, and the IDMC found that 67 deaths (59 percent) occurred in the treatment arm, which received GVAX plus Taxotere (docetaxel, Sanofi-Aventis Group), while 47 deaths (41 percent) occurred in the control arm, which received Taxotere plus prednisone.

On an investor conference call, Cell Genesys CEO Stephen Sherwin called the findings "very disappointing and surprising" and said the company does not know the reason for the imbalance.

He added that the IDMC did not identify any new safety issues that were associated with the GVAX/Taxotere combination.

Cell Genesys plans to analyze patient demographics, disease characteristics, treatment variables and other factors that may have affected the trial outcome.

Sherwin predicted those analyses will take "a couple of months."

In the meantime, the company moved quickly to halt both enrollment and treatment in the randomized, double-blind, controlled Phase III trial, dubbed VITAL-2.

Cell Genesys also is reviewing the situation with partner Takeda Pharmaceutical Co. Ltd., which paid $50 million up front in a potential $320 million deal earlier this year for worldwide rights to GVAX in prostate cancer. (See BioWorld Today, April 2, 2008.)

Cell Genesys' other Phase III trial of GVAX in prostate cancer, VITAL-1, is ongoing.

Enrollment and treatment have been completed, although physicians had the option to continue treating patients with GVAX if they felt there was a benefit, and those treatments will continue.

Data from VITAL-1 are expected in the second half of 2009.

And so the million-dollar question is: Does the VITAL-2 failure foreshadow the outcome of VITAL-1?

Investors seem to think so. They pushed shares of South San Francisco-based Cell Genesys (NASDAQ:CEGE) to new 52-week lows on Wednesday.

The stock closed down $2.01, or 72 percent, to close at 79 cents.

Cell Genesys isn't taking any chances. The company asked the IDMC to conduct a previously unspecified futility analysis of the VITAL-1 trial.

The plan for that analysis will be discussed with the FDA, since the trial was designed under a special protocol assessment, and the outcome is expected within a month.

But analyst Joseph Pantginis, of Canaccord Adams Inc., said he thinks VITAL-1 will succeed. In a research note, he pointed out that VITAL-1 is testing GVAX as a monotherapy rather than in combination with Taxotere, a product he said that is known to be "toxic."

GVAX is not the first product linked to an increase in deaths when combined with Taxotere for prostate cancer. Last year, Novacea Inc. and partner Schering-Plough Corp. terminated a Phase III trial of Asentar (DN-101) due to higher than expected deaths when the drug was combined with Taxotere. (See BioWorld Today, Nov. 6, 2007.)

Pantginis also noted that patients in VITAL-2 were "sicker" than in VITAL-1.

VITAL-2 enrolled metastatic hormone-refractory prostate cancer patients with cancer pain symptoms, while VITAL-1 enrolled earlier stage, asymptomatic patients.

Pantginis emphasized that the VITAL-1 patients are "aligned with the patient population tested in the two independent Phase II studies showing median survival of 35 months" compared to 18 months to 19 months for Taxotere alone.

David Miller, CEO of independent research firm Biotech Stock Research LLC, pointed out that the IDMC has been reviewing VITAL-1 all along and would have stopped the trial if it had concerns.

In January, the committee recommended that the trial continue after a preplanned interim analysis. (See BioWorld Today, Jan. 15, 2008.)

"I don't think you can know what this means for VITAL-1," he told BioWorld Today. Yet he added that even if GVAX gains approval, prostate cancer doctors would likely want to use Taxotere as a fallback option in case treatment with GVAX didn't work, and the VITAL-2 outcome may make them question the safety of using the two drugs together even sequentially.

That factor gives an advantage to Dendreon Corp.'s prostate cancer vaccine Provenge (sipuleucel-T), Miller said.

For those handicapping the race to FDA approval of a therapeutic cancer vaccine, GVAX and Provenge are considered the frontrunners. Interim data from a confirmatory Phase III trial of Provenge are expected in October, but most analysts predict the results will be inconclusive and expect the full data in the second half of 2009, putting Dendreon neck-and-neck with Cell Genesys.

Shares of Dendreon (NASDAQ:DNDN) fell 21 cents to close at $5.73 on Wednesday.

Other cancer vaccines in Phase III include AVAX Technologies Inc.'s melanoma vaccine M-Vax, Bioniche Life Sciences Inc.'s bladder cancer vaccine Urocidin, Oncothyreon Inc.'s lung cancer vaccine Stimuvax, GlaxoSmithKline plc's lung cancer vaccine MAGE-A3 ASCI, Vical Inc.'s melanoma vaccine Allovectin-7, Receptor BioLogix Inc.'s pancreatic cancer vaccine Insegia, and The Vaccine Co.'s PR1 peptide vaccine for acute myeloid leukemia.

Biovest International Inc. reported positive Phase III data last month with non-Hodgkin's lymphoma vaccine BiovaxID, but statistical questions left some investors skeptical.

Meanwhile several cancer vaccines have blown up in late-stage trials this year, including offerings from Oxford BioMedica plc and Favrille Inc.

Cell Genesys reported $166 million in cash and equivalents as of June 30, and the company plans to re-evaluate its business operations in light of the VITAL-2 trial failure. Sherwin said that evaluation will be completed after the futility analysis of the VITAL-1 trial.

Published  August 28, 2008