Effects of Triheptanoin (UX007) in Patients with Long-chain Fatty Acid Oxidation Disorders (LC-FAOD): Results from an Open-Label, Long-Term Extension Study

Background: Long-chain fatty acid oxidation disorders (LC-FAOD) are autosomal recessive conditions that impair conversion of long-chain fatty acids into energy, leading to significant clinical symptoms. Triheptanoin is a highly purified, 7-carbon chain triglyceride approved in the US as a source of calories and fatty acids for treatment of pediatric and adult patients with molecularly confirmed LC-FAOD.

Methods: CL202 is an open-label, long-term extension study evaluating triheptanoin (UX007) safety and efficacy in patients with LC-FAOD. Patients rolled over from the CL201 triheptanoin clinical trial (rollover); were triheptanoin-naïve (naïve); or had participated in investigator-sponsored trials/expanded access programs (IST/other). Results focus on rollover and naïve groups, as pre-treatment data allow comparison. Primary outcomes were annual rate and duration of major clinical events (MCEs; rhabdomyolysis, hypoglycemia, and cardiomyopathy events).

Results: Seventy-five patients were enrolled (24 rollover, 20 naïve, 31 IST/other). Mean study duration was 23.0 months for rollover, 15.7 months for naïve, and 34.7 months for IST/other. In the rollover group, mean annualized MCE rate decreased from 1.76 events/year pre-triheptanoin to 0.96 events/year with triheptanoin (P = 0.0319). Median MCE duration was reduced by 66%. In the naïve group, median annualized MCE rate decreased from 2.33 events/year pre-triheptanoin to 0.71 events/year with triheptanoin (P = 0.1072). Median MCE duration was reduced by 80%. The most common related adverse events (AEs) were diarrhea, abdominal pain/discomfort, and vomiting, most mild to moderate. Three patients had serious AEs (diverticulitis, ileus, rhabdomyolysis) possibly related to drug; all resolved. Two patients had AEs leading to death; neither drug related.

Discussion: Triheptanoin reduced rate and duration of MCEs. Safety was consistent with previous observations. This article is protected by copyright. All rights reserved.