With its first regulatory filing expected this year, Dendreon Corp. is streamlining its efforts for the potential approval and commercialization of its prostate cancer drug, Provenge.

The company cut about 15 percent of its work force, mostly from early stage research and development programs and general and administrative functions, to make way for new manufacturing and marketing jobs in preparation for Provenge approval. Dendreon expects to begin submitting a rolling BLA for the drug around the middle of the year, based on Phase III data showing a statistically significant survival benefit with Provenge in men with advanced forms of the disease. If all goes as planned, the BLA will be in the FDA's hands in the second half of 2006.

This realignment "positions us well this year to get the job done," said Monique Greer, senior director of corporate communications at Dendreon. "For the company to be successful, we've got to get this product through the goal line."

Greer said Dendreon plans to request a priority six-month review by the FDA, which could put Provenge on the market as early as 2007.

Dendreon is laying off 34 of its 230-member staff, though the reduction isn't permanent. The company plans to staff a new Provenge manufacturing facility in East Hanover, N.J., and will need people to handle commercial operations at its corporate headquarters in Seattle.

"So we could actually end the year with more employees than we had" before the cut, Greer told BioWorld Today.

"It's always a tough decision" to lay off employees, she added, "but this puts us on very solid footing to advance Provenge."

As Dendreon's most advanced product, Provenge (sipuleucel-T), an active cellular immunotherapy, could end up also being the first cancer immunotherapy to go before the FDA for approval. The drug is designed to stimulate the immune system to attack cells expressing prostatic acid phosphatase, a protein found on nearly 95 percent of prostate cancer cells. Provenge was developed using Dendreon's Antigen Delivery Cassette technology, which delivers small bits of the PAP protein to cells presenting the antigen, prompting an immune system response to destroy those cells.

The cancer immunotherapy closest in development to Provenge is South San Francisco-based Cell Genesys Inc.'s GVAX, which is in two ongoing Phase III studies in prostate cancer.

But being first can make structuring pivotal trials a challenge. The FDA asked for a disease progression endpoint in the company's first Phase III trial, D9901. That endpoint was missed a year ago, as Provenge failed to show a significant delay in time to disease progression. The company had better news about a month later, after further analysis of the three-year trial data showed compelling survival data: About 34 percent of the patients treated with Provenge remained alive at three years, compared to 11 percent in the placebo arm. (See BioWorld Today, Jan. 12, 2005, and Feb. 18, 2005.)

Since then, the company has maintained that survival data are more indicative of Provenge's activity, since it typically takes eight to 10 weeks for an immunotherapeutic to activate the immune system, while disease progression can occur in nine to 11 weeks.

Those Phase III survival results were confirmed in a smaller 98-patient companion study, completed last summer, and data pooled from both trials showed a statistically significant survival benefit of 23 percent over placebo. (See BioWorld Today, July 22, 2005.)

During the next year, the company will continue funding an ongoing IMPACT (Immunotherapy for Prostate Adenocarcinoma Treatment) Phase III study - formerly D9902B - evaluating the use of Provenge in patients with metastatic, androgen-independent prostate cancer.

"We met with the FDA and expanded the criteria for that trial," Greer said, which now allows all men with prostate cancer to enroll, regardless of their Gleason scores. Previously, the trial required patients with a Gleason score of 7 or less.

Dendreon also amended the primary endpoint of the 500-patient IMPACT study to evaluate overall survival, rather than time to disease progression.

"All the patients enrolled in that study to date will be part of the safety database" for the BLA, Greer said. And full results of IMPACT could be used as a post-approval study or for a label expansion to offer Provenge to a slightly larger prostate cancer population.

Dendreon also announced that Michelle Burris, senior vice president of corporate development and general counsel, is leaving the company, although that move is unrelated to the work force reduction, Greer said. Burris' duties will be taken over by Rick Hamm, senior vice president of corporate development and general counsel, and David Urdal, senior vice president and chief scientific officer.

Dendreon posted a net loss of $19.7 million, or 33 cents per share, for the third quarter. As of Sept. 30, the company had cash, cash equivalents and investments totaling $134.6 million, though it added about $48 million through a public offering of 10 million shares in December. (See BioWorld Today, Dec. 8, 2005.)

Its shares (NASDAQ:DNDN) closed at $5.25 Friday, down 20 cents.