By Karen Pihl-Carey

Cellegy Pharmaceuticals Inc. decided to go forward with a second Phase III trial of Anogesic to treat anal fissures, despite the drug¿s failure to meet its primary endpoint in the first study.

This time the endpoint will be pain relief, the first trial¿s secondary endpoint.

¿We¿re hopeful to begin the trial in the first quarter of next year,¿ said K. Michael Forrest, president and CEO of South San Francisco-based Cellegy. ¿The trial would be roughly half the size of the first trial. We can use the data in the first trial in the NDA [new drug application] filing, and this will be a confirmatory Phase III study.¿

The primary endpoint in the first study, a double-blind, placebo-controlled study of 304 patients, was complete healing. Data showed Anogesic (nitroglycerin ointment) cured patients at a rate similar to placebo, despite earlier clinical studies, in which a cure rate of between 60 percent and 85 percent was observed, compared with a placebo cure rate of between 10 and 20 percent. (See BioWorld Today, Nov. 24, 1999, p. 1.)

While the drug failed to meet the primary endpoint, it showed positive results in reducing pain. Cellegy officials met with an expert group of surgeons concerning the drug. ¿They told us that probably the most important factor in the treatment of a patient with fissures is the control of pain,¿ Forrest told BioWorld Today. ¿Because it¿s most often the pain factor that causes the patient to request a sphincterotomy.¿ The surgical procedure will reduce the pain, but also will result in anal incontinence in up to 35 percent of the cases.

¿We went to the FDA and showed them the data, and they also agreed that pain was an important component in the overall management of the condition,¿ Forrest said, ¿and that they would be willing to accept an NDA that had pain relief as the primary endpoint.¿

Forrest said the company has about two years of cash, a sufficient amount of funds to conduct the Phase III study, as well as other studies expected in 2000. The company expects to begin a pilot study of Anogesic to treat hemorrhoids, a condition that afflicts as many as 10 million people in the U.S. alone, within the next few months. A pilot study to treat pain following hemorrhoid surgery already is under way. The hemorrhoid indication is potentially much larger than the fissure indication.

The Phase III trial in anal fissures will be a multi-center study, but Forrest did not want to comment on the precise sizing of the trial until the FDA responds to a submitted protocol. Cellegy expected to file an NDA for Anogesic in this indication in early 2000, but the failure set the company back six months or more, Forrest said in November.

Aside from the Anogesic ointment, the company is developing a transdermal testosterone gel to treat male hypogonadism and hopes to enter into Phase III trials within the next few months. Cellegy¿s stock (NASDAQ:CLGY) closed Thursday at $3.375, up 3.12 cents.