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Raptor Pharmaceuticals Corp. has announced positive results in its Phase IIa study of oral 4-methylpyrazole (”4-MP”) in subjects with ALDH2 deficiency, or ethanol intolerance, as the initial development stage of its Convivia program.

Convivia is Raptor’s proprietary oral formulation of 4-MP designed to reduce systemic acetaldehyde exposure and related symptoms in ALDH2 deficient persons following alcohol consumption. 4-MP, the active ingredient in Convivia and used in this Phase IIa study, is marketed in an injectible formulation for other indications, but is investigational for treatment of acetaldehyde toxicity associated with ethanol exposure in ALDH2 deficient subjects.

Conducted in Hawaii, the blinded, intra-subject controlled, single dose, dose escalation study enrolled 32 subjects of Japanese descent with a history of symptoms of inborn altered ethanol metabolism with concomitant ethanol exposure. At the time of enrollment, study subjects also submitted to alcohol dehydrogenase (”ADH”) and aldehyde dehydrogenase (”ALDH2″) genotyping. The objectives of the study were to investigate the safety and efficacy of 4-MP as a potential treatment of symptoms resulting from acetaldehyde toxicity in ALDH2 deficient subjects who drink alcohol. The trial also sought to provide information leading to the most efficacious dose and dosage timing range.

The study results demonstrated that the active ingredient in Convivia significantly reduced heart palpitations (tachycardia), which are commonly experienced by ALDH2 deficient people who drink, at all dose levels tested. The study also found that the 4-MP significantly reduced peak acetaldehyde levels and total acetaldehyde exposure in a subset of the study participants who possess specific genetic variants of the liver ADH and ALDH2 enzymes. This subset represents approximately one-third of the ALDH2 deficient adult population.

Ted Daley, President of Raptor’s Clinical Division, stated, “We are encouraged by these results from our Phase IIa study for Convivia. Currently there are no approved treatments for ALDH2 deficiency, and people with this disorder could potentially benefit by lessening their exposure to acetaldehyde, a known carcinogen, and mitigating the unpleasant reactions to drinking. We plan to seek partners with clinical and commercial operations in Asian countries, to continue the development of this product candidate.”

ALDH2 deficiency, sometimes referred to as “Asian flushing syndrome,” is an inherited metabolic disorder affecting 40% to 50% of East Asian populations, impairing the activity of the liver enzyme aldehyde dehydrogenase (”ALDH2″). When people with ALDH2 deficiency drink alcoholic beverages, there is an accumulation of acetaldehyde, a carcinogenic intermediate in the metabolism of ethanol, in blood and tissues. Published retrospective studies have observed a significant correlation between recurrent drinkers with ALDH2 deficiency and an increase in risk for digestive tract cancers, liver diseases, late-onset Alzheimer’s disease and other serious health disorders. In addition to the long-term health risks, elevated acetaldehyde levels produce acute symptoms, including facial flushing, tachycardia (rapid heart rate), headache, nausea and dizziness. Although ALDH2 deficient people suffer from unpleasant reactions and face long-term health risks, a substantial proportion of them are recurring drinkers of alcoholic beverages.

http://www.raptorpharma.com

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