Washington Editor

The virtual firm Trine Pharmaceuticals Inc. is beginning a gender-specific study of a compound called crofelemer in women with diarrhea-predominant irritable bowel syndrome, but the female-only focus isn't so unusual in that indication.

Women typically respond to treatments better than men, said Chairman, President and CEO Mark Skaletsky, though he admitted that researchers are "not exactly sure why." In addition, he noted that the prevalence of the disease is much greater in women than in men - up to 70 percent, by some estimates.

The Waltham, Mass.-based company, which was formerly known as Essential Therapeutics Inc., is considering diarrhea-predominant IBS in women as crofelemer's initial indication.

The Phase IIb study is designed to randomize 240 women in a double-blind fashion to receive either the drug or placebo. The multicenter trial, which will take place in the U.S., is evaluating crofelemer's ability to improve abdominal pain associated with the disease as its primary endpoint.

The product works by blocking the chloride ion secretion via the CFTR channel to normalize water flow in the gut while preventing dehydration.

The study, Skaletsky said, will inform Trine whether or not to proceed further with the compound. "It's been powered to give us the answer," he said. At present, crofelemer represents the only research being undertaken by the privately held firm.

Backed by three venture capital firms, Trine primarily comprises the former management team of GelTex Pharmaceuticals Inc. That business was bought six years ago for $1.3 billion by Genzyme Corp., a deal which brought Renagel (sevelamer) to Cambridge, Mass.-based Genzyme. (See BioWorld Today, Sept. 12, 2000.)

For now, Skaletsky is tight-lipped about crofelemer. "We'll be saying more about it in a couple of months," he said, after Phase IIa results are released at the Digestive Disease Week meeting in April.

The study's initiation triggers a $1 million milestone payment to Napo Pharmaceuticals Inc., which licensed the drug to Trine about a year ago. The deal, which provided worldwide development and commercialization rights in the indication, included an undisclosed up-front payment and also calls for further milestone payments and royalties on sales, should crofelemer eventually receive FDA approval.

The agency has granted it fast-track status in diarrhea-predominant IBS, a disease estimated to affect between 15 percent and 20 percent of the U.S. population.

Crofelemer is extracted from Croton lechleri, a medicinal plant harvested from the rain forests of several South American countries. Napo, of South San Francisco, is testing its use in AIDS diarrhea, acute infectious diarrhea, including cholera, and pediatric diarrhea. All are clinical-stage programs, and the AIDS diarrhea indication also has fast-track status from the FDA. Crofelemer could be on the market by 2008 in that use.

The company went public earlier this year, raising £11.9 million (US$22 million) through an initial public offering on the London Stock Exchange's main market.

On Monday, its shares (LSE:NAPL) fell 5 pence to close at 93 pence. (See BioWorld Today, Aug. 1, 2006.)