Washington Editor

Cellegy Pharmaceuticals Inc. stopped a Phase III study of its microbicide gel for HIV prevention because of a lower-than-expected seroconversion rate.

"The rate of HIV infections in the trial were so low," explained Anne-Marie Corner, the company's senior vice president for women's preventive health, during a conference call, "we would be unable to determine if Savvy was having an effect on HIV transmission."

The decision followed a recommendation by the trial's data monitoring committee, which determined that continuing it would not elucidate the C31G vaginal gel's effect after reviewing interim findings from the Ghanaian study. The estimated annual rate of HIV seroconversion in the study population was 3.7 percent when the trial began last March, but the observed annual rate fell to 1.2 percent after 18 months, possibly due to procedures designed to ensure ethical trial design such as counseling on HIV prevention and distribution of condoms.

"These procedures were essential," Corner said, "and as a result, we can conclude that while perhaps this can be viewed as a public health success, such a low incidence of HIV means the study can no longer answer the question about product effectiveness."

Though she added that it's "too early to tell" whether the stoppage could impact timing of an eventual new drug application for HIV prevention, a similarly structured Phase III study in Nigeria continues to move forward. The NDA had been forecast in 2007, though that timeline could change depending on final analysis of the Ghanaian data and eventual findings from Nigeria.

Nevertheless, the Huntingdon Valley, Pa.-based company stressed that the committee found no evidence of safety concerns related to Savvy, which is applied intravaginally via a pre-filled applicator prior to each act of intercourse, based on its review of the comparative numbers of HIV seroconversions in the Savvy and placebo groups and other interim data. Therefore, Corner concluded that the trial could be considered a successful safety study.

It was halted after Cellegy collectively agreed with Family Health International and the U.S. Agency for International Development, which is funding the trial, though the parties agreed that Savvy should continue to be studied for its effect on preventing HIV transmission. If they had continued the Ghanaian study, it would have required many more participants "to observe the specified number of infections," Corner said, noting that 900 had completed the study in Ghana and another 1,242 will be removed from the trial as it winds down. "In this case," she added, "because the rate of HIV infection was so low, this would have had major logistical and financial repercussions." So instead, they are considering expansion of the ongoing Nigerian trial, and/or opening new sites in areas with higher HIV incidence, all of which could influence NDA timelines down the road.

"Given that we have such good safety data in such a large population, we feel comfortable about expanding our trials into higher-risk populations," Corner said, later adding that efficacy could be better teased out in other people who largely disregard condoms regardless of counseling.

Additionally, the Ghanaian data will be analyzed for effects on other endpoints such as pregnancy, and if warranted, the results will be submitted as a supplemental data package for a contraception NDA still scheduled for 2007. Since the analysis of the HIV data did not indicate any safety concerns, a U.S.-based Phase III trial in that indication is continuing as planned, with enrollment still ongoing. Planning is under way for a second contraception study at other sites in the U.S., and additional studies are planned to examine its effectiveness against other sexually transmitted diseases, such as herpes, in the near future.

Savvy, a clear, odorless gel, is believed to disrupt sperm cell activity as well as that of pathogens that cause sexually transmitted disease.

Beyond that product, the specialty biopharmaceutical company's portfolio includes Cellegesic (nitroglycerin ointment), a product for pain associated with chronic anal fissures that remains under FDA review, following a not-approvable letter a year ago. Branded Rectogesic abroad, it already is marketed in the UK and clearance is being sought in the other member states of the European Union through the mutual recognition procedure. That's also the case for Fortigel (testosterone gel), known as Tostrex overseas, which is marketed in Sweden for male hypogonadism as Cellegy awaits full EU approval.

On Tuesday, the company's shares (NASDAQ:CLGY) fell 7 cents to close at 95 cents.