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Bad news from the FDA for Dendreon Corp. on Provenge for prostate cancer sent the firm's stock into a tailspin and trimmed other cancer-vaccine companies' shares as well, taking away some of the gains made when an advisory panel gave the compound a positive vote in late March.

The FDA is "still a government bureaucracy in defensive mode," said Stephen Dunn, analyst with Dawson James Securities in Boca Raton, Fla., adding that he had seen "no possibility" the agency would clear Provenge, based on the panel vote.

"They get penalized by Congress for approving drugs," he said, referring to the recent debacle over COX-2 inhibitors such as Vioxx. "Why should they stick their neck out?"

Dendreon's shares (NASDAQ:DNDN) tumbled 64.3 percent on the news, closing Wednesday at $6.33, down $11.41. The FDA's approvable letter put investor hopes on results from the ongoing Phase III IMPACT trial with Provenge, due to report preliminary data in the second half of next year or the first half of 2009.

Some on Wall Street had expected Andrew von Eschenbach, head of the FDA, to intervene on Provenge's behalf, Dunn said, since the side effect profile for Provenge is much better than Taxotere (docetaxel, Sanofi-Aventis Group), the current standard treatment. But that didn't happen.

Laying chips on the 500-patient IMPACT study might be risky, since the trial is signing up patients with more advanced disease than in earlier trials, where Provenge managed to show a 21 percent survival benefit. Because drugs that boost the immune system take so long to work, slow-moving prostate cancer is the right target, Dunn said - but sicker patients in the ongoing study could hurt results.

"It doesn't look great," he said. In any case, the FDA wants more clinical data in the existing biologics license application, and Dendreon is asking for clarity on what must be done next, noting that the agency also asked for details regarding chemistry, manufacturing and controls.

Provenge (sipuleucel T) came out of Dendreon's Antigen Delivery Cassette technology, and deploys recombinant prostatic acid phosphatase, an antigen found in most prostate cancers. The company last year let go about 15 percent of its work force from early stage research and development programs and general functions, freeing resources for new manufacturing and marketing jobs ahead of Provenge's launch. (See BioWorld Today, Jan. 23, 2006.)

The Seattle-based firm had based its BLA on results from a smallish D9901A Phase III trial (127 patients), with results added from the second Phase III study, called D9902A. Improvement in overall survival shown in the first trial was achieved by way of a secondary statistical analysis, and Provenge cleared the advisory panel only after FDA reviewers softened their question regarding efficacy. (See BioWorld Today, April 2, 2007.)

The advisory panel's thumbs-up vote (13-4 on efficacy and 17-0 on safety) for leader Provenge had given hope to others in the cancer-vaccine space, and their shares dipped accordingly Wednesday. South San Francisco-based Cell Genesys Inc.'s stock (NASDAQ:CEGE) closed at $4.27, down 28 cents. Favrille Inc. (NASDAQ:FVRL), of San Diego, ended the day at $3.47, down 74 cents. New York-based Antigenics Inc. (NASDAQ:AGEN) fell 34 cents to close at $2.53. Genitope Corp. (NASDAQ:GTOP), of Redwood City, Calif., closed at $3.34, down 42 cents.

"I've been a bear on immunotherapy in oncology in general," Dunn said. "They've never been really successful."

Mitchell Gold, president and CEO of Dendreon, said in a news release: "Given our strong belief in the survival benefit and safety profile of Provenge, coupled with the positive outcome of the advisory committee meeting, we are disappointed that this decision will cause a delay in the availability of Provenge for patients who suffer from advanced prostate cancer. We are committed to working closely with the FDA to resolve these questions in a timely and efficient manner."

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