Patrick Horn, MD, PhD, Chief Medical Officer at HemoShear Therapeutics, discusses the phase 2 HERO trial evaluating HST5040 in patients with methylmalonic acidemia (MMA) and propionic acidemia (PA).
MMA and PA are rare inherited metabolic disorders in which the body is unable to process certain proteins and lipids properly. MMA is characterized by deficiency of methylmalonyl-CoA mutase, while PA is characterized by deficiency of propionyl-CoA carboxylase. These enzymes are directly involved in the breakdown of amino acids as well as cholesterol, certain fatty acids, and other substances necessary for metabolic processes. The deficiency of these enzymes leads to accumulation of these chemicals and metabolites which harms the mitochondria. Symptoms of these disorders are usually apparent during the first weeks of life and may include hypotonia, poor feeding, vomiting, failure to thrive, lethargy, dehydration and seizures. Without appropriate treatment, coma and death may result. MMA and PA patients have to follow a specific diet including a low protein intake and specific food formulas. Liver transplant to decrease the frequency of acute metabolic episodes is also an option.
As Dr. Horn explains, HST5040 is an orphan drug in development that works in both MMA and PA by diverting coenzyme A from methylmalonyl-CoA and propionyl-CoA, resulting in a decrease in methylmalonyl-CoA and propionyl-CoA levels.
Dr. Horn goes on to explain that the HERO study (NCT04732429) is a 3-part phase 2 clinical trial that is currently recruiting patients. Part A is an open-label, within-subject, dose escalation study in PA and MMA subjects ≥ 2 years old to identify an optimal dose of HST5040 for use in Part B. Part B is a 6-month, randomized, double-blind, placebo-controlled, 2-period crossover in the same subjects from Part A to evaluate safety and efficacy of the optimal dose of HST5040 in addition to standard of care. Finally, Part C is an open-label long-term extension study to evaluate the long-term safety and efficacy of the optimal dose of HST5040.
To learn more about MMA, PA, and other metabolic disorders, visit https://checkrare.com/diseases/metabolic-disorders/