By Lisa Seachrist

Washington Editor

Less than a month after an FDA advisory panel unanimously supported NeXstar Inc. and Fujisawa USA Inc.'s bid for approval of AmBisome — their liposomal formulation of amphotericin B — the agency has granted them the broadest label to date for such a preparation.

The agency approved AmBisome as an empiric therapy for suspected fungal infections in patients with fever of unknown origin, as a treatment for patients with confirmed fungal infections who have failed treatment with amphotericin B, and as a therapy for visceral leishmaniasis (a parasitic infection). The company plans to launch the product at the end of September.

"The speed with which this drug was approved reflects the quality of the work done by all parties," said Patrick Mahaffy, president and CEO of NeXstar, in Boulder, Colo. "This application was really well handled by everyone involved and Fujisawa conducted a convincing pivotal trial."

Fujisawa, of Deerfield, Ill., licenses the U.S. and Canadian rights to AmBisome. The companies, which will copromote AmBisome in the U.S. and Canada, have yet to release the price of the injected drug, but it will have to contend with competition from two other lipid preparations of amphotericin B: The Liposome Co.'s Abelcet and Sequus Pharmaceutical's Amphotec. AmBisome, however, is the only product indicated for empiric therapy.

"The intrinsic qualities of AmBisome combined with the strength of this labeling indication should allow us to have a substantial share of the market," Mahaffy said. "We dominate the market in Europe, where we are in competition with the other products; and, ultimately, we intend to play a dominant role in the U.S. as well as overseas."

NeXstar's stock (NASDAQ: NXTR) closed at $14.38, up $0.87.

Invasive fungal infections are particularly common among patients who suffer from neutropenia — low white blood cell counts — as the result of AIDS, chemotherapy or other immune suppression. Typically, a physician presumes such a patient has an invasive fungal infection when he or she has a fever that fails to resolve after standard antibiotic treatment. Doctors usually treat patients on the basis of this presumption because it could be too late for effective therapy if they wait for positive cultures to come back from the lab.

For nearly 30 years, the treatment of choice has been the antifungal agent amphotericin B, which cures approximately 50 percent of all invasive fungal infections. However, the drug can cause irreversible kidney damage.

Lipid formulations of amphotericin B are designed to lower the toxicities of the drug by delivering the drug directly to fungal cells. NeXstar and Fujisawa showed that AmBisome worked as well as amphotericin B but has significantly less kidney toxicity in febrile neutropenic patients. And, as a result of AmBisome's liposomal formulation, doctors can deliver much higher doses of amphotericin B with less toxic effects.

In the U.S. market, AmBisome joins DaunoXome — a treatment for Kaposi's sarcoma — as NeXstar's approved products. The company also is developing a liposomal formulation of the powerful but highly toxic antibiotic amikacin.

"We are at a very exciting time," Mahaffy said. "We expect to file for two investigational new drug applications in the next year and are working to develop a deep pipeline of products." *