West Coast Editor

With the chemistry, manufacturing and controls (CMC) part of its rolling biologics license application for Provenge still to come, Dendreon Corp. submitted the clinical and nonclinical sections to the FDA.

"I wouldn't say one part is harder than the other," said Mitchell Gold, president and CEO of Seattle-based Dendreon, adding that the clinical piece "always gets a lot of scrutiny."

Mark Monane, analyst with Needham & Co. in New York, was cautiously optimistic about the next steps for the prostate cancer drug.

"CMC sections are never in the bag," he said. "They're the most challenging for biotech to do." But the latest news shows Dendreon is meeting its targeted timeline, noted Monane, and Provenge could be reviewed by the FDA in mid-2007.

The company's stock (NASDAQ:DNDN) closed Thursday at $4.48, up 22 cents.

Designed to stimulate the immune system against hormone-refractory prostate cancer (HRPC), Provenge came out of Dendreon's Antigen Delivery Cassette technology, which deploys a recombinant form of prostatic acid phosphatase, an antigen found in 95 percent of prostate cancers.

The Provenge push has been Dendreon's main effort since the first of the year, when the firm let go about 15 percent of its work force from early stage research and development programs and general functions to liberate resources for new manufacturing and marketing jobs in preparation for Provenge approval. (See BioWorld Today, Jan. 23, 2006.)

Since then, Dendreon has focused on construction of the manufacturing plant in Hanover, N.J., and conformance lots have been made by the supplier Diosynth Biotechnology, of Research Triangle Park, N.C., which will be important for the CMC part of the BLA, Gold said.

"Things have progressed very nicely," he said. "We'll submit the CMC by the end of this year, which will start the PDUFA clock." When the BLA is complete, the firm will apply for priority review.

For Provenge, the drug to beat in the marketplace is Taxotere (docetaxel), a chemotherapeutic for breast cancer and non-small-cell lung cancer from the Paris-based Sanofi-Aventis Group. Taxotere won approval in May for prostate cancer and has achieved a survival improvement of about two and a half months.

Dendreon published results of the pivotal Phase III study with Provenge in the July 2006 issue of the Journal of Clinical Oncology, showing a survival benefit of 4.5 months compared to placebo.

Not only is Provenge survival benefit almost twice that of Taxotere, but its side effects are much milder - mainly fever and chills, as opposed to neurotoxicity and gastrointestinal complications with Taxotere, Gold and Monane said.

"People lose their balance and fall down," on Taxotere, noted Monane. "It really hurts the quality of life." Because of the side effects, Gold said, about 50 percent of patients elect not to go on chemotherapy and die earlier.

If approved, Provenge would be the first therapeutic cancer vaccine to treat advanced HRPC. Gold said Dendreon plans to market the compound in the U.S. but will seek a partner outside the country.

"[The U.S.] is a large market, and the size of the sales force we would need is relatively small, approximately 100 sales reps," he said.

Monane pointed out that, although Dendreon seems well on its way to a timely filing of the BLA, no one can accurately predict which FDA panel will review Provenge - or what the recommendation might be.

"It's a risk," he said. "'Novel' is a two-edged sword."