Glenmark Pharmaceuticals' crofelemer, a potential first-in-class innovative drug for multiple indications including HIV-associated diarrhoea, has successfully completed the dose selection stage (Stage I) of the phase III (Advent) trial for the treatment of chronic diarrhoea in people living with HIV/AIDS on antiretroviral therapies. The phase III trials in the United States have conducted by Glenmark's partners Napo Pharmaceuticals and Salix Pharmaceuticals. The final stage of the phase III adaptive study will begin in the treatment of chronic diarrhoea in patients living with HIV/AIDS. Glenmark anticipates the launch of crofelemer in India during 2010

Crofelemer is a first-in-class anti-secretory agent that acts locally in the gastrointestinal tract. Glenmark has crofelemer rights in over 140 countries in the world and expects peak sales opportunity of US$ 80 million in ROW markets in HIV-related diarrhoea indication alone in addition to potential sales in adult acute infectious diarrhoea. Glenmark and Salix have also entered into a commercial supply agreement for the crofelemer API. In addition to customary margins on global supplies, Glenmark would be entitled to receive royalty on sales in the western markets from Napo.

Commenting on this development, Glenn Saldanha, MD & CEO, Glenmark said "With crofelemer progressing to the final stage of phase III trials, we will accelerate the manufacturing scale-up and planning for its anticipated commercial launch. Based on the current progress, we anticipate the launch of crofelemer in India in 2010"

The phase III (Advent) trial is a randomized, double-blind, parallel-group, placebo-controlled, two-stage, adaptive design study. Stage I consisted of 28 days of treatment for three dose groups (125 mg, 250 mg, and 500 mg orally twice daily), and a placebo group, totalling 206 patients, with approximately 50 patients in each group. To select a dose for Stage II, an independent review board conducted an interim analysis of the safety and efficacy of each dose per preset protocol guidelines. This was not a futility analysis, and does not provide the opportunity for the trial to be halted based on efficacy parameters.

The trial will now progress with the addition of 150 patients, 75 of whom will be randomized to the Stage II dose of crofelemer, and the other 75 to placebo. These 150 Stage II patients will be combined, respectively, with the 50 subjects from Stage I who were on the dose selected for Stage II and the 50 who were on the placebo, for a final Stage II patient population of 250 (125 in each group). All patients in the trial will be treated in a five-month extension phase after their 28 day treatment.

Salix Pharmaceuticals, Inc. has licensed the rights to crofelemer from Napo Pharmaceuticals for all indications in North America, Europe (excluding certain smaller countries), and Japan, and, for certain other indications including irritable bowel syndrome, worldwide.