NeXstar Pharmaceuticals Inc. expects to file a new drug application(NDA) with the FDA next month to market AmBisome, a liposomalform of the antifungal agent, amphotericin B.
AmBisome, which is under development with Fujisawa USA, wouldbe NeXstar's second liposomal drug on the market in the U.S.Fujisawa USA, of Deerfield, Ill., is a subsidiary of FujisawaPharmaceutical Co. Ltd., of Osaka, Japan.
Boulder, Colo.-based NeXstar won FDA approval of DaunoXome, aliposomal form of daunorubicin, for AIDS-related Kaposi's sarcomain April 1996.
Liposomes, subcellular spheres made from phospholipids, aredesigned to deliver drugs directly to disease sites, reducing toxicityand boosting effectiveness. Amphotericin B is marketed worldwideas the treatment of choice for fungal infections, but infusions of thedrug can cause serious side effects.
NeXstar is testing AmBisome in the U.S. for fever of unknownorigin, cryptococcal meningitis and histoplasmosis.
The company Tuesday said evaluations from two European Phase IIItrials of AmBisome showed the drug worked at least as well asamphotericin B in treatment of cryptococcal meningitis andaspergillosis with fewer adverse reactions. NeXstar said the data willbe included in the October 1996 NDA submission.
The European study results were presented at the 36th annualInterscience Conference on Antimicrobial Agents and Chemotherapy(ICAAC) Tuesday in New Orleans.
In one trial involving 28 AIDS patients with cryptococcal meningitis,an infection of the central nervous system, investigators concludedAmBisome was at least as effective as amphotericin B. NeXstar'sdrug also generated a significantly lower rate of kidney toxicity thanthe antifungal agent itself.
The second study tested low and high doses of AmBisome fortreatment of aspergillosis in 119 immunocompromised cancerpatients. The infection, which causes lesions, was most prevalent inthe lungs of the study participants.
Data revealed AmBisome achieved partial or complete clinicalresponses in 65 percent of patients whether they received the lowdose or high dose. Kidney toxicity, the study showed, also was aboutthe same at both dose levels.
Although the trial did not compare clinical response rates ofAmBisome to amphotericin B, NeXstar said a U.S. study revealed theconventional therapy against aspergillosis generated partial orcomplete responses in 24 percent of cancer patients.
If AmBisome gets to the U.S. market it will compete with Princeton,N.J.-based The Liposome Co.'s Abelcet, which uses a lipid complexto deliver the amphotericin B. Abelcet was cleared by the FDA latelast year. Sequus Pharmaceuticals Inc., of Menlo Park, Calif., has anNDA under review by the FDA for Amphotec, a lipid-based form ofamphotericin B.
All three products already are sold outside the U.S.
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-- Charles Craig
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