The FDA granted Xoma Corp. a designation that will allow it toexpedite development of Neuprex by moving it directly into a pivotalPhase III trial for severe meningococcemia in pediatric patients.
The agency's Center for Biologics Evaluation and Research grantedSubpart E designation to Neuprex in that indication following arecently completed 16-patient open-label study. The designation wasgiven based on severity of disease, the need for more effectivetherapies and suggestive results from the open-label study, Xoma saidTuesday.
Meningococcemia is caused by the bacterium Neisseria meningitidis,which invades the bloodstream and leads to high levels of endotoxin,a poisonous part of the bacterial cell wall. In some cases the bacteriaand their endotoxin can lead to overreaction of the immune systemand then quickly to serious illness or death. It usually strikes youngpeople.
Xoma's Neuprex is recombinant bactericidal/permeability increasingprotein, or rBPI. BPI is a human host-defense protein produced inwhite blood cells that appears to act by punching holes in thebacterial cell walls, then binding and neutralizing endotoxin, saidEllen Martin, Xoma's director of communications.
Xoma has separate studies of BPI ongoing in three other indications:hemorrhagic trauma, or infectious complications of severe accidentalblood loss; complications following partial hepatectomy, a type ofliver surgery; and in combination with antibiotics to treat intra-abdominal infections, including those resistant to the antibiotic.
Martin said, "To the best of our knowledge this is the first time[Subpart E] has been granted to a biologic." The Berkely, Calif.,company's stock (NASDAQ:XOMA) gained 13 percent, or 63 cents,Tuesday to close at $5.50 in trading of more than one million shares.
The open-label study on which the designation was based involved16 patients and escalating doses of Neuprex. A total of 23 patientsnow have been treated and 22 survived the disease, Xoma said."They are seeing improved morbidity as well, meaning feweramputations," Martin said. "Also we're not seeing neurologic damageafter the fact."
Jack Castello, Xoma's president, chairman and CEO, said in aprepared statement, "This is the first of our Phase II Neuprex trials tobe completed. The study was conceived as a proof of concept fordiseases involving gram-negative bacterial infections with highcirculating levels of bacterial endotoxin, and the results have beenvery enlightening. We have been encouraged by the cooperative andflexible attitude of the FDA in helping us to rapidly move to anappropriate pivotal study for this infectious disease."
Protocols for the pivotal study are being finalized. Patient accrual forsevere meningococcemia can be slow, and depends partly on thenumber of centers that participate in the study. The open-label studytook about one year.
Meanwhile, Xoma and partner Pfizer Inc., of New York, continue towait for word from regulatory officials in Japan on the approvabilityof the monoclonal antibody E5 for endotoxin poisoning. In the U.S.an interim analysis of E5 for gram-negative sepsis in patients withreversible organ dysfunction, made after one-third of 1,700 patientswere enrolled, determined the trial should continue. That trialstemmed from a subset of patients who appeared to benefit in a studyin which E5 did not show survival benefit for gram-negative sepsispatients.
The first interim safety analysis of Neuprex in liver surgery patientshas been completed. Martin said success in that small indicationwould point toward the possibility of Neuprex working in largerindications, such as acute hepatitis. An interim analysis on the first100 patients in the hemorrhagic trauma indication showed no safetyconcerns. Analysis on the first 200 patients now is ongoing, and willinclude a look at efficacy.
For intra-abdominal infections Neuprex is being used as an adjunct tostandard antibiotics. Martin said preclinical results indicated Neuprexmay reverse antibiotic resistance.
Xoma also is working on development of South San Francisco-basedGenentech Inc.'s anti-CD11a monoclonal antibody, now calledhu1124. Martin said an investigational new drug application is beingdeveloped. n
-- Jim Shrine
(c) 1997 American Health Consultants. All rights reserved.