NeXstar Pharmaceuticals Inc. renegotiated a U.S. marketingagreement for AmBisome, a liposomal form of amphotericin B, withFujisawa USA Inc. to recapture some profits from the estimated $200million in potential sales of antifungal agents.
Fujisawa USA, a division of Osaka-based Fujisawa PharmaceuticalCo. Ltd., has Phase III studies of AmBisome under way for treatmentof fever of unknown origin _ the largest market _ and cryptococcalmeningitis.
The Liposome Co., of Princeton, N.J., and Liposome TechnologyInc., of Menlo Park, Calif., also are conducting Phase III trials withliposomal forms of amphotericin B.
Amphotericin B is on the market worldwide and is the first-linetreatment of choice for fungal infections. But infusions of the drugcan cause serious side effects.
Liposomal formulations of amphotericin B are designed to reduceadverse reactions, but their effectiveness as a replacement for nakedamphotericin B is still in question.
Under their previous agreement, Fujisawa USA, of Deerfield, Ill.,received exclusive rights to develop and market AmBisome in theU.S. while NeXstar, of Boulder, Colo., maintained rights to sell theantifungal drug elsewhere.
The original deal was negotiated in 1991 by Vestar Inc., of SanDimas, Calif., which earlier this year merged with NeXagen Inc., ofBoulder, to form NeXstar.
Joseph Alper, NeXstar's director of corporate communications, saidthe amended collaboration gives NeXstar 20 percent of gross profitsfrom U.S. sales in addition to manufacturing rights.
NeXstar's AmBisome has been approved in 16 countries outside theU.S. as a second-line therapy; that is, for use after patients fail torespond to conventional amphotericin B treatments. The companysaid sales in 1994 totaled $43 million.
The amended Fujisawa agreement, announced Thursday, would giveNeXstar access to profits from a U.S. market whose total annual saleshave been estimated as high as $200 million as a first-line treatment.
In return, Fujisawa will receive data from NeXstar's recentlycompleted Phase III trials of AmBisome in Europe for treatment offever of unknown origin in children and adults. In addition, NeXstaragreed to conduct another Phase III trial in the U.S. for AmBisomefor treatment of histoplasmosis in AIDS patients.
All of the additional Phase III trial results, Alper said, will giveFujisawa more supportive efficacy data in its efforts to getAmBisome approved by the FDA.
Results from NeXstar's Phase III European trials will be releasedlater this spring. In general, Alper said, those studies showedAmBisome was at least as effective as amphotericin B and had fewerside effects.
Regulation of liposomal antifungal agents in the U.S. has been afocus of controversy. This week the FDA's Antiviral Drugs AdvisoryCommittee rejected a proposal for an accelerated approval track forthe drugs. Because patient accrual is slow, the usual Phase III studiescould take years to complete.
Fujisawa estimated its Phase III trials of AmBisome for fever ofunknown origin will take another two years to complete with atargeted patient enrollment of more than 600. The Phase III studiesfor cryptococcal meningitis, involving 300 patients, could takelonger.
However, Alper said NeXstar expects to finish its Phase III study inthe U.S. for histoplasmosis in AIDS patients in less than two years.The number of patients involved was not disclosed.
The reputation of liposome technology has been hampered, in part,by rejection of Vestar's DaunoXome in 1993 by the FDA'sOncologic Drugs Advisory Committee.
Alper said that product, the liposomal formulation of daunorubicinfor Kaposi's sarcoma, was submitted for approval based on anaccelerated track. A more complete study, involving 232 patients,was conducted and an amended new drug application was submittedto the FDA in January.
Part of the new agreement between NeXstar and Fujisawa gives theJapanese-based pharmaceutical company first rights to negotiate co-development and co-marketing of DaunoXome in the U.S.
NeXstar's stock (NASDAQ:NXTR) closed Thursday at $6.50, up 12cents. News of the agreement was released after the market closed. n
-- Charles Craig
(c) 1997 American Health Consultants. All rights reserved.