By Karen Pihl-Carey

Cellegy Pharmaceuticals Inc. said pivotal trial data show Anogesic (nitroglycerin ointment) to treat chronic anal fissures cured patients at a rate similar to placebo, failing to reach its primary endpoint.

Investors responded negatively to the news Tuesday, with the company¿s stock (NASDAQ:CLGY) dropping 62 percent to close at $4.093, down $6.78.

The company originally expected to file a new drug application for Anogesic in the U.S. by early next year. The disappointing data set them back about six months or more, said K. Michael Forrest, president and CEO of South San Francisco-based Cellegy.

¿Our intent at this point in time and our expectation is that we will continue to move forward with some revised approach,¿ Forrest told BioWorld Today. ¿If that means doing another trial, then we¿ll do another trial. We would plan on meeting with the FDA as soon as possible.¿

The Phase III double-blind, placebo-controlled study involved 304 patients and was designed to determine the optimum dose and frequency required. Preliminary results showed the primary endpoint of complete healing was not met, while the secondary endpoint of pain reduction was positive. The data are not fully in line with what Cellegy found in previous clinical trials, Forrest said.

¿The reason why we had set the cure as being the primary endpoint was because in earlier clinical studies we observed a cure rate of between 60 [percent] and 85 percent,¿ Forrest said. ¿And the level of placebo response in earlier studies was between 10 [percent] and 20 percent.¿

The earlier trials, which involved more than 400 patients, indicated Anogesic reduced pain and cured many patients over an eight-week course of therapy. In a study published in The Lancet, about 68 percent of patients who would have required surgery were cured, while only 8 percent of those on placebo experienced the same reaction.

But in the Phase III trial, about 44 percent of patients treated with the most effective dose of Anogesic experienced a complete cure of their condition, while a ¿similar, inexplicably high percentage¿ of patients treated with a vehicle ointment containing no active drug also were cured, the company said.

¿What went wrong? We¿re analyzing the data to try to understand better what might have happened, but we don¿t know yet exactly what went wrong,¿ Forrest said. ¿We¿re convening an expert group to meet with us here [next week] to review all the data and our analysis, which will be more thorough then, in an attempt to decide what the next steps might be in terms of a redesign of the study or of how we might submit the data to the FDA.¿

The only significant difference between Anogesic and the placebo in the Phase III trial seemed to be the level of pain felt by the patients. Those taking Anogesic reported a significantly greater decrease in pain, compared with those taking placebo.

¿There was a very statistically strong outcome in terms of reducing pain,¿ Forrest said. ¿Since pain is a major component of fissures and of hemorrhoids, we still are very confident that one way or another we will have a product.¿

The company expects to begin a pilot study of Anogesic to treat hemorrhoids within the next few months. A pilot study to treat pain following hemorrhoid surgery already is under way. The Phase III data of Anogesic will not affect the hemorrhoid studies, Forrest said, adding the hemorrhoid indication is potentially much larger than the fissure indication, with about 10 million people affected in the U.S.

¿There is no drug that has proven effective [and is FDA- approved] in the treatment of hemorrhoids,¿ he said. ¿So as such, this would be the first product approved by the FDA should we be able to prove efficacy.¿

Forrest said the company will know within three to four weeks whether it will conduct another pivotal trial in anal fissures and how the design might be different.

Taking Anogesic into a second Phase III trial would not be a financial problem for the company, said Richard Juelis, vice president of finance and chief financial officer at Cellegy.

¿Our financing position is pretty strong,¿ he told BioWorld Today. ¿We¿re well positioned at least to redo and continue the program.¿

Cellegy raised $10.1 million in the summer through a private placement to help fund the completion of the Phase III trial of Anogesic, as well as trials of its other products. (See BioWorld Today, Aug. 3, 1999, p. 1.)

As of the company¿s third quarter ended Sept. 30, Cellegy had cash and investments of $18.6 million. The company posted a net loss for the quarter of $1.9 million, or 17 cents a share, and revenues of $25,000.

In addition to Anogesic ointment, Cellegy is developing a transdermal testosterone gel to treat male hypogonadism, which can result in decreased energy and libido in men. Upon FDA approval, the company plans to enter into Phase III trials with the gel within the next few months.

Glylorin (monolaurin), the company¿s product to treat congenital ichthyosis, a skin disorder, is on the back burner right now, while Cellegy seeks a partner to develop it in Europe, Forrest said. Glylorin was given FDA approval last year to enter Phase III trials, but partner Glaxo Wellcome Inc., of London, returned its rights to the product in order to concentrate its resources elsewhere. Cellegy intends to retain rights to the product in the U.S.