Aronex Pharmaceuticals Inc. started Phase III trials of its leadproduct, a liposomal formulation of the antifungal agent nystatin.
The trial will compare intravenous Nystatin (LF) to amphotericin Bin a double-blind trial involving about 200 cancer patients withpresumed fungal infections who do not respond to antibacterialtherapy. The study will be conducted at about 20 U.S. centers.
Nystatin has been available for more than 40 years as an antifungalagent, but its toxicity limited its use to topical applications. Aronex,in collaboration with the M.D. Anderson Cancer Center, in Houston,developed the liposomal formulation.
"The company's Phase II results strongly suggest that Nystatin (LF)possesses a better safety profile and is more active on a mg/kg basisthan competitive products on the market or currently in clinicaldevelopment," Aronex President James Chubb said. "The Phase IIItrial is designed to further document the safety and efficacy ofNystatin (LF)."
The Woodlands, Texas, company, however, is not disclosing Phase IIdata pending its presentation and publication, said Barbara Kennedy,Aronex's senior director, clinical research operations.
Kennedy said the Phase II trial is an ongoing open-label study inculture-proven candidemia in non-neutropenic patients. "The onlything we can say is the data suggests that 2 mg/kg per day to be aneffective antifungal therapy with a strong safety profile."
The Phase III study will be in those with presumed fungal infection,including those who do not respond to standard broad-spectrumantibiotics, Kennedy said. Patients will be evaluated at the end oftreatment and 30 days post-treatment. The primary endpoint will besubsidence of fever, she said.
Aronex is seeking a partner for Nystatin, Kennedy said.
Aronex's development of Nystatin is behind at least two othercompetitors that are developing lipid or liposomal antifungals. Theother companies, however, are using formulation of amphotericin B.
The Liposome Co., of Princeton, N.J., got approval last November ofAbelcet to treat refractory aspergillosis. Sequus Pharmaceuticals Inc.,of Menlo Park, Calif., filed a new drug application for its Amphotecin November. And NeXstar Pharmaceuticals Inc., of Boulder, Colo.,is developing a liposomal antifungal in the U.S. and selling it inEurope, where its product sells better than Amphotec or Abelcet.Aronex doesn't compete in Europe.
Nystatin (LF) was studied in a Phase I trial in HIV patients, anindication which currently isn't being pursued.
Aronex is developing Tretinoin, a liposomal formulation of all-transretinoic acid, with Genzyme Corp., of Cambridge, Mass. The drug isin Phase II/III studies in Kaposi's sarcoma and refractory acutepromyelocytic leukemia.
A liposomal form of anthracycline, called Annamycin, recently wastaken into Phase I studies for multidrug-resistant breast cancer. Thatstudy is being conducted under a physician's investigational newdrug application at M.D. Anderson.
Those three drug candidates represent the pipeline of the formerArgus Pharmaceuticals Inc., which completed a triple merger lastSeptember with Oncologix Inc. and Triplex Pharmaceuticals Corp.(See BioWorld Today, Sept. 7, 1995, p. 1.)
From Triplex came AR177, a guanine-thymine oligonucleotide, that'sin Phase I studies for HIV.
Aronex's stock gained 63 cents on Tuesday's announcement of themove into Phase III and was unchanged Wednesday at $5. n
-- Jim Shrine
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