Triheptanoin for the treatment of long‐chain fatty acid oxidation disorders: Final results of an open‐label, long‐term extension study

• DOI: 10.1002/jimd.12640
• Publication Date: 2023-06-07T06:51:10Z
• Authors: Jerry Vockley; Barbara K. Burton; Gerard Berry; Nicola Longo; John Phillips; Amarilis Sanchez‐...; Kimberly A. Chapman; Pranoot Tanpaiboon; Stephanie Grunewald; Elaine Murphy; Xiaoxiao Lu; Syeda Rahman; Kathryn Ray; Bridget Reineking; Laura Pisani; Antonio Nino Ramirez
• Keywords: Interquartile range; Clinical endpoint

Long-chain fatty acid oxidation disorders (LC-FAODs) result in life-threatening energy metabolism deficiencies/energy source depletion. Triheptanoin is an odd-carbon, medium chain triglyceride (that anaplerotic substrate of calories and acids) for treating pediatric adult patients with LC-FAODs. Study CL202 (NCT02214160), open-label extension study CL201 (NCT01886378), evaluated the long-term safety/efficacy triheptanoin LC-FAODs (N = 94), including cohorts who were naïve (n 33) or had received 24) investigator-sponsored trials/expanded access programs (IST/EAPs; n 37). Primary endpoint was annualized rate LC-FAOD major clinical events (MCEs; rhabdomyolysis, hypoglycemia, cardiomyopathy). Mean ± standard deviation (SD) treatment durations 27.4 19.9, 46.9 13.6, 49.6 21.4 months triheptanoin-naïve, rollover, IST/EAP cohorts, respectively. In triheptanoin-naïve cohort, median (interquartile range [IQR]) MCE significantly decreased from 2.00 (0.67-3.33) events/patient/year pre-triheptanoin to 0.28 (0.00-1.43) (p 0.0343), a reduction 86%. rollover mean SD 1.76 1.64 1.00 0.0347), 43%. 1.40 2.37 (median [IQR] 0.57 [0.00-1.67]) triheptanoin. Safety data consistent previous observations. Treatment-related treatment-emergent adverse (TEAEs) occurred 68.1% mostly mild/moderate severity. Five seven serious treatment-related TEAEs; all resolved. Our results confirm efficacy LC-FAOD.