Dextofisopam, a non-serotonergic agent currently being evaluated for the treatment of irritable bowel syndrome (IBS), is the R-enantiomer of racemic tofisopam, a molecule marketed and used safely outside the United States for over three decades for multiple indications including IBS. Dextofisopam represents a novel, first-in-class opportunity with a positive proof-of-concept study in an arena where there are few compounds with unique approaches or positive efficacy results. By structure, dextofisopam is a member of the homophthalazine class; dextofisopam binds to specific receptors in areas of the brain affecting autonomic function, including gastrointestinal (GI) function. Unlike 5-HT3 or 5-HT4 IBS therapies currently available, both with significant safety concerns, dextofisopam's novel non-serotonergic, 'brain-gut' mechanism offers a unique and innovative approach to IBS treatment.
A double-blind, placebo-controlled diarrhea-predominant or alternating
IBS Phase 2a study has been completed with positive effect on primary
efficacy endpoint (n=141, p=0.033). In this study, dextofisopam was
well-tolerated and demonstrated significant improvement over placebo
suggesting that dextofisopam has the potential to become a novel
first-line treatment for IBS. As the announced in March, 2009, the Company has determined that a 300 patient trial
should be of sufficient size to achieve its objectives. Consequently, the current
Dextofisopam trial targeting 480 patients will be reduced to 300 patients. This trial will
continue to have four cohorts of female patients. Each cohort will have approximately 75
patients. There are three drug cohorts at 100 mg BID, 200 mg BID, and 300mg BID and
placebo.
An extensive patent estate is in place with dextofisopam and owned by Pharmos. This consists of an issued composition-of-matter patent, an issued method-of-use patent, and numerous additional pending patent applications in both the United States (including use of dextofisopam for inflammatory disorders and immunomodulation) and foreign counterparts.
IBS
IBS is a chronic, recurring condition with symptoms that affect more than 10% of Americans, more often women than men. IBS is characterized by multiple symptoms that include bowel dysmotility - diarrhea, constipation, or alternating diarrhea and constipation - and abdominal discomfort. Diarrhea-predominant IBS appears to be the most common subtype. For patients with diarrhea-predominant and alternating-type IBS, there are no recently approved treatments for any but the most severely affected women, and none for men.
The Dextofisopam phase 2a results produced a P = 0.037 (N = 141). These results were
published in the British Journal, Alimentary Pharmacology & Therapeutics in January
2008.
