Washington Editor

Shares in Polydex Pharmaceuticals Ltd. lost more than half their value on news that two Phase III trials of its HIV prevention product have been halted.

The product, called Ushercell, is a cellulose sulfate-based vaginal microbicide being developed to prevent the virus from infecting women. But a reproductive health research organization called the Program for Contraceptive Research and Development (CONRAD), which is conducting one of the studies, halted it because preliminary results at some trial sites indicated that cellulose sulfate instead could lead to potential increased risk of HIV infection in women who use the topical gel.

Specifically, there was a higher seroconversion rate in those who received the investigational product than in placebo patients, although numbers weren't disclosed.

Despite the discrepancy between findings at various sites, it remains too early to speculate whether any environmental or other factors contributed to the higher risk, said Linda Hughes, who heads investor relations for Toronto-based Polydex.

"CONRAD has to be left to do its evaluation of the data," she told BioWorld Today, "and determine what the biological cause of that unexpected increase. At this time, the patients appear to be without irritation, so there's nothing immediately evident."

That trial was being conducted in South Africa, Benin, Uganda and India, and as a precautionary measure, a second study being conducted by Family Health International was halted in Nigeria, even though it did not detect an increased HIV risk associated with cellulose sulfate.

An independent data monitoring committee will conduct a detailed review of the data to better understand the findings, and help determine any implications for other microbicide studies. Cellulose sulfate, a cotton derivative, is one of four microbicides that's been in effectiveness testing to prevent HIV and other sexually transmitted infections. The others are based on different compounds.

"We really had high hopes for this," Hughes said. She added that despite the setback, the data are "helpful to the rest of the microbicide pipeline" because such information will provide researchers "more tools to better develop future models on how to design" such trials.

The double-blind study of Ushercell, which began a year and a half ago, randomized women to receive either cellulose sulfate or a placebo gel. All participants received HIV prevention counseling at each monthly visit and received free condoms, as well as regular testing and treatment for sexually transmitted infections. Pregnant women were not included.

In the aggregate, nearly 5,000 women were to be recruited to the CONRAD and Family Health International studies. Hughes said it's not yet known exactly how far enrollment had progressed, but they were expected to last about four years, a period that includes recruitment, testing, follow-up and analysis.

Both trials were being funded through $24 million in grants, with half from the Bill & Melinda Gates Foundation and the remainder from by the U.S. Agency for International Development (USAID). It was hoped that the studies would demonstrate a decrease of at least 50 percent in HIV incidence among Ushercell users compared to placebo. (See BioWorld Today, May 9, 2005.)

The product's safety profile hasn't been flagged in the past, Hughes said, with more than 500 participants receiving it in 11 previous clinical trials before the HIV prevention studies. Animal testing also has shown a good safety profile for Ushercell.

The earlier human testing evaluated its use as a contraceptive, with Phase II data to date demonstrating its effectiveness in preventing pregnancy. Specifically, Ushercell proved more than 85 percent effective against pregnancy, Hughes said.

Phase III plans for the product's contraceptive use remain in the works, with that testing to be conducted by CONRAD, a program administered through the Department of Obstetrics and Gynecology at Eastern Virginia Medical School in Norfolk, Va., with its main office in Arlington, Va.

Other clinical studies have evaluated Ushercell's use for preventing and treating bacterial vaginosis, but data aren't yet available. Preclinical trials have demonstrated its potential against gonorrhea, chlamydia and herpes I and II.

Polydex said halting the HIV trials wouldn't affect its financial situation. Wednesday, its stock (NASDAQ:POLXF) fell $3.66, or 55 percent, to $3.