By Mary Welch
Phase III data showed Nyotran, a liposomal formation of nystatin developed by Aronex Pharmaceuticals Inc., was equivalent to amphotericin B but had less renal toxicity in treating patients with systemic fungal infections.
"The results from the study showed that there was statistically significant data concerning equivalency as defined by the protocol," said Tony Williams, vice president of medical affairs of Aronex. "The data show that the two are equivalent. It shows that Nyotran consistently displayed a very broad spectrum of activity, especially toward refractory organisms."
The Phase III trial involved 538 neutropenic patients who had failed previous antibacterial therapy. They were treated at more than 200 sites in the U.S., Europe, South Africa and Australia. In the modified intent-to-treat population, 36 percent - or 65 of the Nyotran patients - were deemed successfully treated in comparison to 66 amphotericin B patients, or 39 percent.
The results were scheduled to be presented Monday at the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy in San Francisco.
While successful treatment differed by only 3 percentage points, Williams said the toxicity data were more divergent.
"Patients taking amphotericin B experience significantly more renal adverse events and hypokalemia," he said. "They also had a significantly greater frequency of metabolic and nutritional disorders compared with Nyotran patients. When I would go to the center the nurses would tell me about having to give potassium supplements to amphotericin B patients. Now when you're trying to treat a leukemia patient, you don't want to be worrying about giving oral potassium supplements. You want to avoid that at all costs. It's not a medical emergency but it can put the patient at risk. You don't have that potassium problem with Nyotran."
Nyotran belongs to a class of drugs known as polyene derivatives, which include amphotericin B, the standard treatment for systemic fungal infections. Traditionally, nystatin has been used as a topical treatment because it was too toxic to be taken systemically, said Geoffrey Cox, Aronex's chairman and CEO. "With the liposomal formulation, Nyotran has indicated it has a low toxicity profile and has shown activity against several resistant organisms. We believe the data show that Nyotran could be a new front-line treatment for systemic infections. It can treat a variety of infections and has a good safety profile," he said.
Nyotran was partnered with Abbott Laboratories, of Abbott Park, Ill., last year in a deal worth up to $40 million. (See BioWorld Today, Nov. 17, 1998, p. 1.)
Aronex, of The Woodlands, Texas, plans on filing a new drug application (NDA) by year's end. However, Cox said, there is more work to be done before the filing can be made.
In addition to this Phase III for presumed fungal infections, the company has finished enrolling patients in a Phase III trial for Cryptococcal meningitis. That trial still is blinded but results should be coming out soon, Cox said.
A Phase II trial using Nyotran in patients with life-threatening Candida (yeast-based) infections was completed, and the drug is in another Phase II trial for an Aspergillus salvage indication, which is a mold-based infection.
"We want to be able to get the complete results and analyze the results," Cox said. "We want no hiccups here so we're being very persnickety about it. Our goal is an NDA filing this year but we have a significant amount of work to do since we'll be including four different studies - two Phase IIIs and two Phase IIs."
Cox can perhaps be excused for being "persnickety" after an FDA committee's decision last month not to consider Atragen, Aronex's lead drug. The Oncologic Drugs Advisory Committee notified the company it would not review Atragen, an injectable liposomal formulation of all-trans retinoic acid, due to deficiencies it uncovered. The drug was for the treatment of patients with acute promyelocytic leukemia. (See BioWorld Today, Aug. 16, 1999, p. 1.)
"It's still the status quo," Cox said. "We've had no further information about what the nature of those deficiencies are. We're in constructive discussions but we have had nothing clarified."