A New Drug Application (NDA) has been submitted to the Food and Drug Administration (FDA) for triheptanoin (Ultragenyx) for the treatment of long-chain fatty acid oxidation disorders.

Triheptanoin is a medium-chain triglyceride that bypasses the genetic block in long-chain fatty acid metabolism. According to the Company, one of the Krebs cycle intermediates generated by triheptanoin, can also be converted to glucose, potentially providing an additional therapeutic effect. Patients with long-chain fatty acid oxidation disorders are unable to convert long-chain fatty acids into energy which can lead to severe glucose depletion. 

The NDA was supported by data from an open label phase 2 study assessing the safety and clinical effects of triheptanoin in 29 patients with a confirmed diagnosis of carnitine palmitoyltransferase (CPT II) deficiency, very long chain acyl-CoA dehydrogenase (VLCAD) deficiency, long-chain 3-hydroxy-acyl-CoA dehydrogenase (LCHAD) deficiency, and trifunctional protein (TFP) deficiency.

Results showed that treatment with triheptanoin led to a 48% reduction in the mean annualized rate of major clinical events (aggregate of events related to hypoglycemia, cardiomyopathy, and rhabdomyolysis). In addition, there was a 50% reduction in the mean annualized duration of all major clinical events after 78 weeks of treatment, compared with the mean annualized number and duration of events in the 18 to 24 months prior to triheptanoin treatment. With regard to safety, the most common treatment-related adverse events were diarrhea, abdominal/gastrointestinal pain, and vomiting.


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Additional data from a long-term safety and efficacy extension study (N=75), a retrospective medical record review, and a randomized controlled investigator-sponsored study (N=32) were also included in the submission. Sixty-seven patients were also treated with triheptanoin through an expanded access program.

“Many patients with long-chain fatty acid oxidation disorders have difficult lives with frequent hospitalizations despite the best current care, and we believe our data suggest that treatment with [triheptanoin] can reduce these major medical events over a sustained period of time,” said Camille L. Bedrosian, MD, Chief Medical Officer of Ultragenyx. “The submission of this NDA is an important step toward providing a new treatment option and we look forward to working with the FDA on this review.”

For more information visit ultragenyx.com.