The FDA has informed Xoma Corp. that data from the firstclinical trial of its E5 treatment for sepsis does not providesufficient evidence of efficacy for marketing approval, thecompany said Tuesday.
Xoma's announcement, which came after the close of themarket, said that the product license application for themonoclonal antibody is still before the FDA, pending theagency's review of a second multicenter study.
Xoma shares (NASDAQ:XOMA) lost 25 cents to $18.50, but weredown sharply in after-hours trading. Rival Centocor Inc.'s stockdropped $2.50 to $31.25.
"For Xoma to get any approval at all would be quite a feat," saidPrudential analyst Joseph Edelman. "Any way you slice it, E5isn't going to be approved for awhile, if ever. The stock shouldbe down 8 points on Wednesday if there's any sense in theworld."
Edelman, long a Xoma bear, said the stock is worth about $4 --a price at which the company might be an attractive acquisitioncandidate for a suitor interested in MAb expertise.
David Stone, a Cowen & Co. analyst who has come down on theother side of the Xoma-Centocor debate, still believes the drugwill be approved. "Until I had additional information, I wouldcontinue to think that the combined data package looksapprovable, but only the FDA knows for sure," he said. "Thenagging question is why send this letter. I'm waiting for anexplanation of that."
The first clinical trial of E5 in 468 patients, published lastAugust in the Journal of the American Medical Association,showed that the agent failed to increase survival followinggram-negative sepsis, although reversal of organ failures in theantibody-treated patients did occur significantly morefrequently than in a placebo-treated group.
Survival rates also increased by a factor of 2.3 for patients whoreceived the anti-endotoxin drug before they had developedcirculatory shock.
Both Edelman and Stone agreed that the consensus amongXoma watchers has been that the first clinical trial wasn'tsufficient for approval, which means that E5's fate hinges onthe second trial.
That study, which enrolled almost twice the number ofpatients, has not yet been published. Company spokeswomanCarol DeGuzman declined to give details on its results beforepublication, which she said should occur later this year.
However, details of the study were revealed during last year'spatent infringement trial between Xoma and Centocor, whoserival MAb is awaiting final FDA approval.
According to Edelman, a total of 811 patients were analyzed inthe study, 530 of whom had gram-negative sepsis. Of thatgroup, the mortality rate among treated patients was 30percent, compared with a 26 percent rate in the placebo group.
"So the second study looked worse than the first," Edelmanconcluded.
"I would call that a seductive but superficial analysis," Stonecountered. "You have to look at any imbalances in theunderlying condition of patients in the subsets, and it's ourunderstanding that there were imbalances. If you make thoseadjustments, you don't see any differences."
The real question, Stone said, is whether the FDA is going toallow a meta-analysis of data combined from the two trials.Schering-Plough's alpha interferon for hepatitis B wasapproved using such combined data, he said.
Edelman said he didn't think a meta-analysis is likely giventhat the FDA's letter stated it was finished with the first study.
Xoma of Berkeley, Calif., also announced Tuesday that theEuropean Patent Office on April 8 issued a notice of allowabilityon a patent application that covers claims similar to those ofthe issued U.S. patent on E5 as a sepsis treatment.
-- Karen Bernstein BioWorld Staff
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