Editor

SAN FRANCISCO - As a Pacific storm cleared after dumping days of rain on northern coastal California, the sun shone intermittently on the 23rd annual JPMorgan Healthcare Conference here, the way the figurative sun shines intermittently on the industry itself, with winners and losers, big and small.

JPMorgan's event, which ended Thursday, kicked off Monday in the Westin St. Francis Hotel, as usual. The top news du jour from a presenting company on opening day: Regeneron Pharmaceuticals Inc.'s $50 million gain from VEGF Trap partner Sanofi-Aventis Group. Of the amount, $25 million is a milestone payment related to ongoing work against cancer.

The other half of the Sanofi-Aventis payout relates to a new agreement giving Regeneron all rights to VEGF Trap when administered locally in eye indications. Leonard Schleifer, Regeneron's president and CEO, told BioWorld Financial Watch that the vascular endothelial growth factor technology has yielded "unequivocal data in primates that you can have a dramatic response in models of [age-related macular degeneration]. It binds both the long and short form of VEGF, and we think both of them are important players."

Half of the second $25 million is repayable to Sanofi-Aventis after VEGF Trap is commercialized. In October, Regeneron and Sanofi-Aventis said VEGF Trap had been granted fast-track status by the FDA in an undisclosed "niche cancer indication," with a clinical trial in that indication to start this year.

"There was huge anticipation here," Schleifer said at the conference. "Investors wanted to know how Sanofi would come out on the VEGF Trap." The potential $485 million deal was signed in the fall of 2003. Roger Longman, publisher of In Vivo magazine, speaking at the 2004 JPMorgan conference, called the collaboration "the single most important licensing deal of last year, in terms of early stage deals." (See BioWorld Financial Watch, Jan. 19, 2004.)

Procter & Gamble Co. had rights to VEGF Trap originally but "gave it back because it didn't have any value in muscle-wasting disease, which is what they were thinking about creating it for," Longman said. "What you don't know is what is going to come back and bite you later," he added.

Chomping a 26 percent chunk out of Dendreon Corp.'s stock price was news disclosed Tuesday (when the company's CEO spoke at the JPMorgan conference) that interim data from a Phase III, 98-patient trial with Provenge, known as D9902A, showed the drug failed to reach statistical significance in the primary endpoint - delay of time to disease progression - in the overall group and Gleason score subgroups.

But an interim analysis of overall survival in the intent-to-treat patient population, which is the secondary endpoint, found that survival rates and median survival benefit compared to placebo worked out similar to the results in the final, three-year survival analysis of the 127-patient D9901 study, reported in October.

"The Street's saying, That's very good, but we don't know what D9901 looks like yet," Mitchell Gold, president and CEO, told BioWorld Financial Watch. "They want to see that data."

Final D9901 results, including three-year survival numbers, are due at the American Society of Clinical Oncology's 2005 Prostate Cancer Symposium in February. Meanwhile, Dendreon is keeping mum per ASCO's embargo policy.

D9902A, designed as a companion study to be pooled with results from D9901, has since morphed into the D9902B pivotal Phase III study, which is ongoing under a special protocol assessment agreement with the FDA under fast-track status.

Provenge, designed to stimulate the immune system against prostate cancer, was developed through 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 headlines sparked renewed talk about one of biotechnology's more challenging indications.

"There've been a number of high-profile attempts to show a survival benefit in prostate cancer," Gold acknowledged. Sanofi-Aventis' Taxotere (docetaxel), a chemotherapeutic for breast cancer and non-small-cell lung cancer, won approval in May for prostate cancer and has shown promising results, but Gold thinks Provenge can do better.

Not everyone is so certain of success, at least not soon. Needham & Co. downgraded Dendreon to "buy" Tuesday, and MDB Capital Group downgraded the stock to "neutral." Brean Murray & Co. reduced its Dendreon rating to "sell" way back in November, with analyst Jonathan Aschoff calling the move "long overdue."

Aschoff said in a research note that the information disclosed so far about D9901 "lends itself easily to hiding important points," such as how many patients with Gleason scores of 8 to 10 "are even alive at three years," and whether the number would be enough "to make a real difference between the results of the entire intent-to-treat population and the subgroup with Gleason scores of 7 and below."

If the three-year data are driven mainly by the healthier subgroup, "that would marginalize the relevance of Provenge to the sicker patients and undercut Dendreon's conclusion that the three-year survival data are truly relevant to the entire intent-to-treat population," Aschoff wrote.

Gleason scores of 7 and below represent 70 percent of patients when first diagnosed with prostate cancer, but they account for only 30 percent of androgen-independent (or hormone-refractory) prostate cancer patients, "which is the only market relevant to all of Dendreon's Phase III trials, in our view," the note said.

The Prostate Cancer Foundation last year released a manuscript titled "Report to the Nation on Prostate Cancer 2004," examining possible treatment options available and those in development, with pointed mention of Provenge, an autologous CD54-positive dendritic cell vaccine loaded with a recombinant fusion protein made of a prostatic acid phosphatases and granulocyte macrophage colony-stimulating factor. (See BioWorld Financial Watch, Oct. 4, 2004.)

A more recent report by Decision Resources cites a handful of novel compounds as likely market drivers in prostate cancer, including Abbott Laboratories' ABT-627, also known as Xinlay (atrasentan), Bristol-Myers Squibb Co.'s BMS-247550 (ixabepilone), GPC Biotech AG's JM-216 (satraplatin) - and Provenge.

"We have three ways to win," Gold told investors at the JPMorgan conference. That is, by affecting disease progression, pain or survival.

"Based on clinical trial data published to date, we assume these [new] agents will be used to treat only late-stage prostate cancer," said the Decision Resources report. "However, if they are approved for earlier-stage disease, they would have an enormous impact" on the market, and "there is a good scientific rationale for this scenario," although not much public data exist yet, the report noted.

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