this is what we dont want to happenSecond Phase III Ongoing
By Trista Morrison
Staff Writer
In yet another setback for cancer vaccines, Cell Genesys Inc.terminated one of its two Phase III trials with prostate cancer vaccineGVAX.
The trial's independent data monitoring committee(IDMC) recommended the action after a routine safety review on Tuesdayturned up an imbalance in deaths between the treatment and control armsof the study. Specifically, 114 out of 408 patients in the trial died,and the IDMC found that 67 deaths (59 percent) occurred in thetreatment arm, which received GVAX plus Taxotere (docetaxel,Sanofi-Aventis Group), while 47 deaths (41 percent) occurred in thecontrol arm, which received Taxotere plus prednisone.
On an investor conference call, Cell Genesys CEOStephen 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, diseasecharacteristics, treatment variables and other factors that may haveaffected the trial outcome.
Sherwin predicted those analyses will take "a couple of months."
In the meantime, the company moved quickly to halt both enrollment andtreatment in the randomized, double-blind, controlled Phase III trial,dubbed VITAL-2.
Cell Genesys also is reviewing the situation with partner TakedaPharmaceutical Co. Ltd., which paid $50 million up front in a potential$320 million deal earlier this year for worldwide rights to GVAX inprostate 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 hadthe option to continue treating patients with GVAX if they felt therewas 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 SanFrancisco-based Cell Genesys (NASDAQ:CEGE) to new 52-week lows onWednesday.
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 toconduct a previously unspecified futility analysis of the VITAL-1trial.
The plan for that analysis will be discussed with the FDA, since thetrial was designed under a special protocol assessment, and the outcomeis expected within a month.
But analyst Joseph Pantginis, of Canaccord AdamsInc., said he thinks VITAL-1 will succeed. In a research note, hepointed out that VITAL-1 is testing GVAX as a monotherapy rather thanin 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 whencombined with Taxotere for prostate cancer. Last year, Novacea Inc. andpartner Schering-Plough Corp. terminated a Phase III trial of Asentar(DN-101) due to higher than expected deaths when the drug was combinedwith 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 patientswith cancer pain symptoms, while VITAL-1 enrolled earlier stage,asymptomatic patients.
Pantginis emphasized that the VITAL-1 patients are "aligned with thepatient population tested in the two independent Phase II studiesshowing median survival of 35 months" compared to 18 months to 19months for Taxotere alone.
David Miller, CEO of independent research firmBiotech Stock Research LLC, pointed out that the IDMC has beenreviewing VITAL-1 all along and would have stopped the trial if it hadconcerns.
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 doctorswould likely want to use Taxotere as a fallback option in casetreatment with GVAX didn't work, and the VITAL-2 outcome may make themquestion 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 ofa therapeutic cancer vaccine, GVAX and Provenge are considered thefrontrunners. Interim data from a confirmatory Phase III trial ofProvenge are expected in October, but most analysts predict the resultswill be inconclusive and expect the full data in the second half of2009, 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 AVAXTechnologies Inc.'s melanoma vaccine M-Vax, Bioniche Life SciencesInc.'s bladder cancer vaccine Urocidin, Oncothyreon Inc.'s lung cancervaccine Stimuvax, GlaxoSmithKline plc's lung cancer vaccine MAGE-A3ASCI, Vical Inc.'s melanoma vaccine Allovectin-7, Receptor BioLogixInc.'s pancreatic cancer vaccine Insegia, and The Vaccine Co.'s PR1peptide vaccine for acute myeloid leukemia.
Biovest International Inc. reported positive PhaseIII data last month with non-Hodgkin's lymphoma vaccine BiovaxID, butstatistical questions left some investors skeptical.
Meanwhile several cancer vaccines have blown up in late-stage trialsthis year, including offerings from Oxford BioMedica plc and FavrilleInc.
Cell Genesys reported $166 million in cash andequivalents as of June 30, and the company plans to re-evaluate itsbusiness operations in light of the VITAL-2 trial failure. Sherwin saidthat evaluation will be completed after the futility analysis of theVITAL-1 trial.
Published August 28, 2008