The FDA's Oncologic Drugs Advisory Committee on Thursdayvoted unanimously not to approve DaunoXome, Vestar Inc.'sliposome formulated anti-cancer agent daunorubicin, fortreating AIDS-related Kaposi's sarcoma (KS) in patients forwhom conventional chemotherapy has failed or beencontraindicated.

As a result of the decision, Vestar's stock (NASDAQ:VSTR)tumbled $2.88 a share on Thursday, closing at $8.13.

Vestar had submitted its new drug application (NDA) forDaunoXome to FDA on Feb. 24, based on Phase II clinical trialdata. At the time, trial data were available on about 150patients with advanced KS who had been treated withDaunoXome, according to Roger Crossley, Vestar's president andchief executive officer.

Crossley also told BioWorld in February that "over 90 percentof the patients get a benefit from the drug. The 60 percent whomet the clinical trial group criteria had a response; that is, acertain percentage of their lesions either shrank ordisappeared. And about 30 percent benefited, although theydidn't meet the criteria."

But when it came to analyzing the data, the FDA committeecame to drastically different conclusions about the drug'sability to benefit KS patients.

"We had a unanimous 'no' vote based primarily on adiscrepancy in the way the company analyzed the data and theway that FDA analyzed the data," said Michael Hart, chieffinancial officer of the San Dimas, Calif., company. "We didn'tknow there was a discrepancy before the meeting took place,"Hart told BioWorld.

In Vestar's analysis of the data, which in the end represented39 patients, Hart, who attended the committee meeting, says"we said we had a 53 percent response rate to the drug, whileFDA said the response rate was 17 percent."

That was FDA's take based on Vestar's data and criteria fordefining "response." But when FDA applied the more rigorouscriteria afforded by historical studies, it found that theresponse rate dropped to less than 3 percent (one patient in39), said Richard van den Broek, an analyst with Oppenheimer& Co., who also attended the meeting. "Vestar wasn't eventrying to compare its data to historical controls," he toldBioWorld.

"It's an exercise in what qualifies as a partial or stable responsein the context of the analysis," explained Vestar's Hart. "Weused the AIDS Clinical Trial Group data to define those, and weare confident that the company did not misrepresent the data."But what isn't clear to Vestar, Hart told BioWorld, is what FDA'sdefinitions were. "We need to know their method of analyzingthe data."

Before proceeding any further, Vestar intends to meet withFDA to determine what the differences are, Hart said.

Vestar is currently conducting Phase III trials comparing itsliposomal formulation of daunorubicin (also known asadriamycin) with standard combination chemotherapy(bleomycin, vincristine and adriamycin).

"FDA expressed an interest that the Phase III trials continue,"said van den Broek. That's a different type of trial than thePhase II, said Oppenheimer's Jeff Casdin. The Phase II trial wasopen label, and the Phase III is a double-blind controlled trial.

Even so, after Thursday's proceedings, "Vestar's got a long wayto come back," Casdin said. The company "has opened the doorwide to competitors," he said. "The advisory panel itself hasprovided a roadway to approval."

-- Jennifer Van Brunt Senior Editor

(c) 1997 American Health Consultants. All rights reserved.

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