West Coast Editor

Less than a month after getting a special protocol assessment from the FDA for the second Phase III trial with its GVAX prostate-cancer vaccine, Cell Genesys Inc. is restructuring to beef up its efforts with the vaccine in several indications while dropping others.

Specifically, the firm is closing its San Diego manufacturing plant and cutting the employee roster by one-fourth, or 95 workers, by the end of the year in order to move ahead with the GVAX Phase III prostate cancer trial, Phase II trials with GVAX for leukemia and pancreatic cancer, and further work with CG0070, in Phase I/II trials for recurrent bladder cancer.

The changes are expected to reduce annual operating expenses by about 15 percent, excluding one-time personnel-related costs of about $1.9 million. Cell Genesys' stock (NASDAQ:CEGE) dipped almost 13 percent on the news, closing Tuesday at $4.79, down 71 cents.

"I think it's a good move," said Buddy Lyons, analyst with Stanford Financial Group in Memphis, Tenn., adding that he was not surprised, given that the South San Francisco-based company is down to $190 million in financial assets.

"People are somewhat disappointed, because they were looking for the lung program to be the early entrance into the market," he told BioWorld Today. Some investors believed positive Phase II data might persuade the FDA to clear GVAX, "but we didn't expect that to happen," he said.

Going by the wayside are GVAX programs for lung cancer and myeloma, which, though they have yielded positive data, were deemed more challenging than the other GVAX efforts. The vaccines are made of tumor cells irradiated and genetically modified to secrete granulocyte macrophage-colony stimulating factor. Cell Genesys has all rights to the GVAX portfolio, since a deal with Tokyo-based Japan Tobacco Inc. for the lung cancer indication ended more than two years ago. (See BioWorld Today, Oct. 21, 2002.)

The lung and myeloma GVAX versions were personalized, whereas pancreatic, prostate and leukemia versions are made out of certain antigens common to each type of cancer, Lyons noted.

"I'm not saying [non-personalized] vaccines have a better chance, per se," he said. "I'm saying it's an easier regulatory path," which is probably why the company is going that route. Whether personalized vaccine works better than non-personalized, or the other way around, is "the great debate," he said.

Lyons was hard pressed to predict where the most promise now lies in GVAX.

"I think they can do well in prostate cancer, but those are long trials," he said. "Pancreatic cancer still offers a really good opportunity, and we'll have to see what happens with the data there. That might be another entrée for them into the marketplace, but I wouldn't bank on any of that."

Cell Genesys has been in something of a race with Dendreon Corp., of Seattle, which late last month said Phase II data suggest the company's Provenge as a single agent might lead to improved prostate-specific antigen doubling time in patients with early stage prostate cancer. Dendreon offered results of the open-label trial at the American Urological Association annual meeting in San Antonio, and said enrollment soon will finish in an ongoing large Phase III study in patients with androgen-dependent prostate cancer.

In February, Dendreon reported data from a Phase III trial, called study D9901, that indicated patients given Provenge showed a four and a half month improvement in median survival, and a greater than threefold increase in survival at 36 months vs. patients who got placebo. (See BioWorld Today, Feb. 18, 2005.)

Cell Genesys, Lyons said, is "pretty confident they're going to have a vaccine that's much more broadly used than Dendreon's," even if the firm is behind Dendreon clinically.

At the American Society of Clinical Oncology meeting last month, Cell Genesys reported additional good results from a second Phase II trial of GVAX in patients with metastatic hormone-refractory prostate cancer (HRPC). Results in the 22 patients who received the highest dose (one comparable to the dose in the ongoing Phase III study) indicated that the median survival has not been reached - and that the final median survival will be no less than 24.1 months based on the current median follow-up time for those patients.

Previously reported findings from the company's first Phase II trial showed an overall median survival of 26.2 months, and the median survival results from both Phase II trials compared favorably to median survival of 18.9 months for HRPC patients treated with Taxotere (docetaxel, from Paris-based Sanofi-Aventis Group) plus prednisone, which is the current standard of care.

So advanced is Provenge, though, that one concern for Cell Genesys has been whether its approval might damage patient enrollment in GVAX trials, though Lyons doesn't think so. Dendreon's product, he said, targets a "narrow spectrum of patients" - those with Gleason scores of 7 and below. Dendreon's research has shown Provenge delays the onset of disease-related pain in those patients.

In the oncolytic virus therapy area, Cell Genesys is scrapping development of the Phase I/II compound CG7870 for prostate cancer, moving ahead with CG0070, which may work against varying tumor types other than bladder cancer. Oncolytic virus products once included a handful of active projects, and the area was the subject of a $28.5 million deal with Basel, Switzerland-based Novartis AG signed in the summer of 2003. (See BioWorld Today, July 23, 2003.)

"I don't think they needed all those," Lyons said. "Working on them all at the same time was overkill." The research, anyway, "is so early stage that nobody cares," he added.

At the end of the first quarter, Cell Genesys said financial assets included about $145 million in cash and 6.6 million shares of former subsidiary Abgenix Inc., of Fremont, Calif.