Martin Pharmaceuticals’ LIVANTRA® is a repurposed, reformulated liquid version of the drug trimetazidine.
Trimetazidine dihydrocholoride (1-(2,3,4-trimethoxybenzyl) piperazine dihydrochloride) was first authorized for use and sale in France in 1978 and is currently marketed in several countries around the world, but not in the USA. An anti-ischemic compound, trimetazidine has principally been used in the treatment of angina pectoris. Trimetazidine has an excellent safety and tolerability profile.
ELIGIBLE FOR MARKET EXCLUSIVITY
Trimetazidine has never been approved by the U.S. FDA for any indication, qualifying it as a new chemical entity (NCE). NCEs are eligible for 5 years of exclusivity from the U.S. FDA. This exclusivity runs in parallel to the 7-year exclusivity granted under the FDA’s orphan drug program.
TRIMETAZIDINE’S MECHANISM OF ACTION
Trimetazidine inhibits beta-oxidation of fatty acids, which enhances glucose oxidation, preventing a decrease in intracellular ATP levels, thereby restoring cellular homeostasis.
At the molecular level, Trimetazidine inhibits ß-oxidation of free fatty acids (FFA) by selectively inhibiting the long-chain 3-ketoacyl coenzyme A thiolase, which is the final enzyme in the FFA ß-oxidation pathway. This interferes with the Randle cycle, resulting in a shift in the utilization of substrate for energy production, inhibiting fatty acid oxidation (FAO) and promoting glucose oxidation (GO) instead.