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

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 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.