Convivia™ for ALDH2 Deficiency

Raptor is developing Convivia™, an oral formulation of 4-methylpyrazole (4-MP) for the potential treatment of acetaldehyde toxicity resulting from ALDH2 deficiency. Sometimes referred to as ethanol intolerance or "Asian flush," ALDH2 deficiency is an inherited metabolic disorder affecting 40-50% of East Asian populations.

ALDH2 deficiency impairs the activity of the liver enzyme ALDH2, the second enzyme of the primary metabolic pathway for ethanol and other alcohols. The result is an accumulation of acetaldehyde, a carcinogenic intermediate in the metabolism of ethanol, in blood and tissues of affected persons who drink alcoholic beverages.

In recurrent drinkers, this disorder has been associated with increased risks of digestive tract cancers and other serious health problems.1, 2

In addition to these long-term serious health risks, elevated acetaldehyde levels lead to immediate and unpleasant symptoms including facial flushing, tachycardia (rapid heart rate), headache, nausea and dizziness.

Currently, 4-MP is the active pharmaceutical ingredient in an existing intravenous product for unrelated indications. Raptor designed Convivia™ to potentially lower systemic acetaldehyde levels and reduce symptoms associated with alcohol intake by ALDH2-deficient individuals.

Development Status for Convivia™ for ALDH2 Deficiency

In 2008, Raptor completed a Phase 2a dose escalation clinical trial of Convivia™ taken concomitantly with alcohol, at a clinical research center in Honolulu, Hawaii. This study 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 active ingredient in Convivia™ 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 estimated to occur in about 15-20% of East Asians.

Raptor is seeking partnerships with pharmaceutical companies in selected Asian countries to continue clinical development of Convivia™ in those countries.


Learn more about Raptor’s other clinical programs:

References:

  1. Seitz HK, Hoffman N. The role of acetaldehyde in alcohol-associated cancer of the gastrointestinal tract. Novartis Foundation Symposium 285 - Acetaldehyde-Related Pathology: Bridging the Trans-Disciplinary Divide. John Wiley & Sons; 2007:110-124.
  2. Blushing from alcohol signals cancer risk for East Asians, USA Today, March 23, 2009.