It's been a long road, but Cellegy Pharmaceuticals Inc. finally found the data it needs for its lead drug, Cellegesic.
The product, a nitroglycerin ointment designed to treat anal fissure pain, demonstrated statistical significance in its primary endpoint in a confirmatory Phase III trial. The company expects to file a new drug application by the end of June. FDA approval could come as early as the end of the year.
"This is obviously a very important day for Cellegy," CEO Michael Forrest said in a conference call. "It's something that we've been working very hard at."
However, he admitted the company has had "some ups and downs."
The company withdrew an NDA for Cellegesic in April 2002 when the FDA said the company did not prespecify the statistical method used to analyze trial results. (See BioWorld Today, April 29, 2002.)
But, Forrest said, the company "always thought this would be an approvable product."
In August, Cellegy began enrolling patients in another Phase III trial to confirm two earlier studies, but conducted the double-blind, placebo-controlled trial according to a Special Protocol Assessment (SPA), meaning the FDA agreed that the achievement of the primary endpoint would be viewed as supporting approval.
The trial included a total of 187 patients during the first 21 days of treatment. They were randomized to receive either placebo ointment or Cellegesic (0.4 percent nitroglycerin ointment). Of the 89 Cellegesic-treated patients and the 98 placebo-treated patients, the primary endpoint of reduction in pain was achieved (p<0.05). The most common side effect, as seen in earlier trials, was mild to moderate headache, which caused five people to drop out of the trial.
At the time of withdrawing the NDA for Cellegesic, the FDA had raised concerns related to the headaches experienced by 50 percent of patients in the previous Phase III trial. Despite the headaches, only 5 percent of patients dropped out of that trial. (See BioWorld Today, April 29, 2002, and Sept. 10, 2002.)
The SPA specified how the dropouts would be treated in evaluating the confirmatory trial's data. For three people who dropped out due to nitroglycerin-induced headache before day 21, their last daily pain intensity score was carried forward to day 21. For two people who dropped out for headaches not due to nitroglycerin, all of their pain data were used to estimate their pain score through day 21. The company, which consulted FDA advisers, believes it has complied with the SPA and that approval for the product is forthcoming. The FDA, of course, will conduct its own analysis of the data.
"Nitroglycerin headaches are very typical," Forest said, explaining how the company deciphered the difference in the five dropouts. "Typically, they will be experienced within the first 30 minutes following the administration of the drug. If it happens after 30 minutes, usually it's not associated with nitroglycerin."
While the SPA mainly is concerned with the primary endpoint, the company also gathered data for a secondary endpoint - time to 50 percent pain reduction - which did not reach statistical significance with Cellegesic. On average, Cellegesic patients reached a 50 percent reduction in pain about a week sooner than placebo patients, Forrest said. Tertiary endpoints included reduction of average pain over the eight-week treatment period, reduction of pain upon defecation through three weeks and eight weeks of treatment, and healing. Cellegesic reached significance with average pain reduction over eight weeks and with defecation pain reduction over eight weeks, but it lost that significance after applying adjustment to the "p" values for the analysis of multiple endpoints.
"It's only being dropped out of significance by virtue of a penalty factor," Forrest said.
With the tertiary endpoint of healing, Cellegesic showed no significant difference from placebo.
The company will seek a priority review from the FDA, meaning approval could come as early as six months from filing. If the company does not receive priority review, it expects to receive approval by early in the second quarter of 2005.
Cellegesic helps to relax the sphincter muscle, reducing the need for surgery in anal fissure patients. Cellegy plans to market the product itself in the U.S. and find a partner for Europe. Forrest would not comment on the company's financial outlook for the drug.
"We do expect good things from Cellegesic and we expect it to become a cash-positive product in a relatively short period of time after launch," he said.
Aside from Cellegesic, the company is studying Tostrelle in a Phase II trial for female sexual dysfunction. In an interim analysis, 71 percent of patients showed positive improvement in sexual activity vs. 13 percent of patients on placebo. Cellegy expects to soon begin a trial of Tostrelle in dyspareunia, a painful condition that makes it difficult for more than 5 million U.S. women to have sexual intercourse.
The company received a non-approvable letter from the FDA in July for its testosterone gel, Fortigel, to treat hypogonadism. The FDA questioned safety of the drug due to high supraphysiological testosterone levels. (See BioWorld Today, July 8, 2003.)
Cellegy submitted a proposal recently to the FDA in order to reach an agreement on any remaining work that might be required for approval.
The company's stock (NASDAQ:CLGY) jumped $1.10 Tuesday, or 20.1 percent, to close at $6.39.