Pfizer Japan, Xoma Corp.'s development and marketing partnerfor the anti-endotoxin monoclonal antibody E5, has submittedan application in Japan for marketing approval of the drug,Xoma said.
The filing is based on Phase III trials conducted by Pfizer inJapan, with Xoma's (NASDAQ:XOMA) U.S. data included assupplemental information. The results of the Japanese trial ofsepsis patients are not yet available. However, Patrick Scannon,Xoma's chief medical officer, indicated that the endpoints usedin the Japanese studies are different than those in the U.S.trials. The primary endpoint in the two U.S. Phase III studieswas survival at day 30.
The two Phase III trials Xoma completed in the U.S. in patientswith suspected Gram-negative sepsis did not show sufficientdrug efficacy to warrant FDA approval.
In the first trial, E5 improved survival only in a retrospectivelyidentified subgroup of patients who were not in refractoryshock. The company then conducted a second Phase III trial inpatients with suspected Gram-negative sepsis who were not inshock, and the drug produced a trend toward decreasedmortality only in some retrospectively identified subsets ofpatients who had certain types of organ failure.
In June the company began a third Phase III trial in patientswith documented Gram-negative sepsis who experienced organfailure. That trial is expected to be completed in 18 to 24months.
FDA denied approval of E5 in April 1992, stating that the firsttrial did not show sufficient efficacy. Two months later theagency told Xoma the second Phase III study was alsoinadequate.
Sepsis drugs have not fared well, but despite disappointingclinical results, Xoma and other companies are continuing topursue their development.
Specifically, Centocor Inc. (NASDAQ:CNTO) is conductingadditional Phase III testing of its monoclonal antibodyCentoxin, and Synergen Inc. (NASDAQ:SYGN) is pursuingadditional tests of its Antril recombinant interleukin-1receptor.
Under the Pfizer/Xoma agreement, Pfizer has rights to marketthe drug in Japan.
Xoma of Berkeley, Calif., noted that this is the first filing forregulatory approval for marketing of an anti-endotoxinmonoclonal in Japan. Xoma has also filed for E5 approval inEurope through the Committee on Proprietary MedicinalProducts (CPMP) and is in discussions with the UnitedKingdom's Medicines Control Agency. The U.K. is serving asXoma's rapporteur (representative) with the CPMP.
-- Brenda Sandburg News Editor
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