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

Abstract

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