Washington Editor

Cellegy Pharmaceuticals Inc. said Wednesday it filed a new drug application for Cellegesic, a proposed treatment for pain associated with chronic anal fissures.

The firm is requesting priority review, meaning FDA action could come within six to 10 months, David Karlin, Cellegy's vice president of clinical research, told BioWorld Today.

Cellegesic, a nitroglycerin ointment, also is being studied in hemorrhoids and dyspareunia, a condition that prevents or inhibits sexual intercourse in more than 5 million women in the U.S., the company said.

But for now, it's pain associated with anal fissures. Company officials said the NDA is based on favorable data from three Phase III trials.

The third Phase III - initiated in August as a means of confirming data from two earlier trials - was a double-blind, placebo-controlled study run according to a special protocol assessment, a procedure in which the FDA agrees that achievement of a pre-specified endpoint would be viewed as supporting approval. (See BioWorld Today, Jan. 28, 2004.)

Indeed, the 187-patient study hit its primary endpoint of reduction in pain (p<0.05). Participants were randomized to either the placebo ointment or nitroglycerin ointment, and daily records of 24-hour average pain intensity from the 89 Cellegesic-treated and 98 placebo-treated patients were analyzed for statistical evidence of efficacy during the first 21 days of treatment as the primary efficacy endpoint.

Meanwhile, the secondary endpoint was time to 50 percent pain reduction. On average, the time produced by Cellegesic was sooner than the time produced by the placebo, although the difference was not statistically significant, the company said.

As for healing, Jack Chandler, vice president of corporate development for South San Francisco-based Cellegy, said in the eight-week trial, about 70 percent of patients did heal, but the figure was not statistically significant.

Data from the trial are being packaged with two earlier trials that were the subject of an NDA filed more than two years ago. Cellegy withdrew the NDA in April 2002 when the FDA said the company had failed to pre-specify the statistical method used to analyze the trial results. (See BioWorld Today, April 29, 2002.)

Karlin said the new NDA includes a re-analysis of the first two trials using the same methods and criteria used in the third trial.

Statistical analyses of combined data from all three trials (704 patients) in patients who used either Cellegesic or placebo roughly every 12 hours showed that 24-hour average pain intensity was significantly reduced through the first 21 days and continued for the balance of the eight-week treatment period, the company said.

Also in the combined data, time to 50 percent improvement in 24-hour average pain intensity was significantly shortened, and pain intensity during defecation was significantly reduced through 21 and 56 days.

Headache was the most common side effect in the studies; however, its incidence was similar to that described for nitroglycerin products used to treat angina. Relatively few patients discontinued treatment due to headache, the company said.

An anal fissure is a tear in the lining of the anal canal and is associated with increased pressure in the anal canal and a decrease in blood supply. Chronic fissures often are treated with a surgical procedure, which may leave up to 35 percent of patients with fecal incontinence.

Cellegy believes Cellegesic could help avoid the risk of surgery by relaxing the sphincter muscle. Fecal incontinence has not been associated with Cellegesic.

Cellegy anticipates regulatory action in Europe by the end of the year, and Chandler said the company expects to seek a marketing partner in Europe, but not in the U.S.

Cellegy's stock (NASDAQ:CLGY) fell 12 cents Wednesday to close at $3.90.