Xoma Corp. hopes the third time will be a charm for its E5 anti-infective, which is entering a third Phase III trial for thetreatment of sepsis.
"It will be the first trial ever with any of these (anti-infective)products to enroll patients with only Gram-negative sepsis,"Xoma spokeswoman Carol DeGuzman said. "We think we'vehoned in on the group that is most likely to benefit from E5therapy," she continued, adding, "We've made a majorinvestment in E5 and would like to bring the product throughlicensure."
The FDA failed to find sufficient evidence of efficacy formarketing approval in 1991, and told the company last year,following a larger second Phase III trial, that additional clinicaltesting may be warranted.
Xoma's rival, Centocor Inc. (NASDAQ:CNTO) of Malvern, Pa., hasdropped its human anti-endotoxin monoclonal antibody,Centoxin, for nearly all indications, and Synergen Inc.(NASDAQ:SYGN) of Boulder, Colo., has stumbled with its ownanti-sepsis compound, Antril, which did not have statisticallysignificant results in a Phase III trial analyzed in February,although the company said the interleuken-1 receptorantagonist appeared to help the sickest patients.
Analyst David Stone of Cowen & Co., who once predicted E5would receive approval, said Tuesday the chances appear lessoptimistic. His associate Carol Werther said the complexity ofseptic shock, a blood infection with a rapid onset whose stagesare hard to differentiate in the clinic, makes it questionablethat a trial can be designed to show that a compound such asXoma's mouse monoclonal antibody against Gram-negativeendotoxin has a benefit, even if it does intercept the sepsiscascade.
The third multicenter trial of the Berkeley, Calif., company'scompound will be managed and co-funded by marketingpartner Pfizer Inc. The trial's design will be based on guidelinespublished by the Infectious Diseases Society of America in theApril 1992 issue of the Journal of Clinical Infectious Diseases.The lead author of the guidelines, Richard Wenzel, performedclinical trials of E5.
In Xoma's first trial, of 468 total patients, 137 who had Gram-negative sepsis but no shock appeared to benefit.
The guidelines call for only enrolling patients with evidence oforgan dysfunction and only those with Gram-negative sepsis.Evidence of this infection can be revealed within an hour witha Gram stain, DeGuzman said, and in previous E5 studies, about70 percent of patients also had bacterial cultures documentedbefore they entered into the study.
She added that clinical definitions to be used wererecommended by a "recent consensus" of physicians from theAmerican College of Chest Physicians and the Society of CriticalCare Medicine.
E5 registration is also being pursued in Europe and Japan, thecompany said.
Xoma (NASDAQ:XOMA) has another compound, CD5 Plus, underFDA review for graft vs. host disease in bone marrowtransplantation. Ortho Biotech, a division of Johnson & Johnson,is the marketing partner for that product.
Receiving the most research attention at Xoma is a humanbactericidal protein, BPI, which is intended to disrupt the cellwall integrity of Gram-negative bacteria and neutralizeendotoxin, the poison that launches septic shock, which canlead to organ failure and death.
The federal Centers for Disease Control and Prevention reportthat there are more than 200,000 cases of Gram-negativesepsis in the U.S. annually and about 70,000 deaths.
Xoma's stock closed at $6.56 a share on Tuesday, down 6 cents.
-- Nancy Garcia Associate Editor
(c) 1997 American Health Consultants. All rights reserved.