OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Triheptanoin – Dojolvi®

DRUG CLASS

Nutritional Supplements

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

View in own window

DRUG	CAS REGISTRY NUMBER	MOLECULAR FORMULA	STRUCTURE
Triheptanoin	620-67-7	C24-H44-O6

ANNOTATED BIBLIOGRAPHY

References updated: 10 June 2024

Abbreviations: LC-FAOD, long-chain fatty acid oxidation disorders; MCT, medium-chain triglycerides; ULN, upper limit of normal range.

• FDA. Integrated Review. 2020.
• https://www​.accessdata​.fda.gov/drugsatfda_docs​/nda/2020/213687Orig1s000IntegratedR.pdf

  (FDA website with integrated review of data on triheptanoin safety and efficacy submitted in support of the application for approval as therapy of long-chain fatty acid oxidation disorders (LC-FAOD), mentions laboratory abnormalities found during therapy include elevations in CPK [71%], ALT [72%], and AST [67%] which are greater than 5 times the ULN in 47%, 24%, and 15%, the elevations however, were attributed to the underlying disease not to triheptanoin).
• Vockley J, Marsden D, McCracken E, DeWard S, Barone A, Hsu K, Kakkis E. Long-term major clinical outcomes in patients with long chain fatty acid oxidation disorders before and after transition to triheptanoin treatment--A retrospective chart review. Mol Genet Metab. 2015;116(1-2):53-60. [PMC free article: PMC4561603] [PubMed: 26116311]

  (In a retrospective analysis of 29 patients with LC-FAOD treated with triheptanoin [providing 28% of daily caloric intake] for 78 weeks, the annualized rate of major clinical events [rhabdomyolysis, hypoglycemia, myocardiopathy] decreased by 48% compared to previous therapy with standard MCT [providing 17% of daily caloric intake]; no mention of adverse events).
• Gillingham MB, Heitner SB, Martin J, Rose S, Goldstein A, El-Gharbawy AH, Deward S, et al. Triheptanoin versus trioctanoin for long-chain fatty acid oxidation disorders: a double blinded, randomized controlled trial. J Inherit Metab Dis. 2017;40:831-843. [PMC free article: PMC6545116] [PubMed: 28871440]

  (Among 32 patients with LC-FAOD treated with either triheptanoin or trioctanoin for 4 months, slight improvements in cardiac function was found with the 7 carbon but not the 8 carbon triglyceride, while adverse events were similar with the two products; no mention of ALT elevations or hepatotoxicity).
• Hainque E, Caillet S, Leroy S, Flamand-Roze C, Adanyeguh I, Charbonnier-Beaupel F, Retail M, et al. A randomized, controlled, double-blind, crossover trial of triheptanoin in alternating hemiplegia of childhood. Orphanet J Rare Dis. 2017;12:160. [PMC free article: PMC5625655] [PubMed: 28969699]

  (Among 10 patients with alternating hemiplegia of childhood treated with triheptanoin or placebo in a cross-over design, there were no differences in paroxysmal events between the treatment and placebo periods and adverse event rates were similar [50% vs 70%] and triheptanoin was considered “well tolerated”; no mention of ALT elevations or hepatotoxicity).
• Vockley J, Burton B, Berry GT, Longo N, Phillips J, Sanchez-Valle A, Tanpaiboon P, et al. UX007 for the treatment of long chain-fatty acid oxidation disorders: Safety and efficacy in children and adults following 24 weeks of treatment. Mol Genet Metab. 2017;120:370-377. [PubMed: 28189603]

  (Among 29 patients with LC-FAOD treated with triheptanoin for 24 weeks, improvements in exercise tests occurred in most patients tested and adverse events were frequent, most commonly diarrhea, nausea, vomiting and abdominal pain; no mention of ALT elevations or hepatotoxicity).
• Schiffmann R, Wallace ME, Rinaldi D, Ledoux I, Luton MP, Coleman S, Akman HO, et al. A double-blind, placebo-controlled trial of triheptanoin in adult polyglucosan body disease and open-label, long-term outcome. J Inherit Metab Dis. 2018;41:877-883. [PubMed: 29110179]

  (Among 19 patients with adult polyglucosan body disease treated with triheptanoin or vegetable oil for one year, there were no differences in changes in 6-minute walk test or in adverse event rates, most of which were considered unrelated to the therapy; no mention of ALT elevations or hepatotoxicity).
• Merritt JL 2nd, Norris M, Kanungo S. Fatty acid oxidation disorders. Ann Transl Med. 2018;6:473. [PMC free article: PMC6331364] [PubMed: 30740404]

  (Review of fatty acid oxidation disorders, a series of rare [1:5000-1:10,000 births] severe autosomal recessive conditions due to inability to metabolize fatty acids to enter the citric acid cycle for energy production; having variable presentations, neonatally typically with cardiomyopathy, in childhood with hypoglycemia and liver dysfunction [Reyes-like syndrome of acute fatty liver], in adolescence with episodic rhabdomyolysis; treated with avoidance of fasting, a fat-restricted diet, aggressive treatment of intercurrent illnesses, and for LC-FAOD, supplementation with MCT; no discussion of adverse events with therapies).
• Borges K, Kaul N, Germaine J, Kwan P, O'Brien TJ. Randomized trial of add-on triheptanoin vs medium chain triglycerides in adults with refractory epilepsy. Epilepsia Open. 2019;4:153-163. [PMC free article: PMC6398112] [PubMed: 30868125]

  (Among 34 adults with refractory epilepsy treated with titrated triheptanoin or conventional medium-chain triglycerides for 15 weeks, there were no differences in rates or changes in seizure frequency or in rates of adverse events and all blood tests showed no clinically significant changes).
• Shirley M. Triheptanoin: First Approval. Drugs. 2020;80:1595-1600. [PMC free article: PMC7575481] [PubMed: 32897506]

  (Review of the structure, mechanism of action, history of development, clinical efficacy, and safety of triheptanoin shortly after its approval for use in the US, mentions that it is “generally well tolerated” and that most adverse events are mild-to-moderate [diarrhea, abdominal pain, nausea and vomiting], or are due to the underlying condition [fatigue, rhabdomyolysis, myalgia]; no mention of ALT elevations or hepatotoxicity).
• Vockley J, Burton B, Berry G, Longo N, Phillips J, Sanchez-Valle A, Chapman K, et al. Effects of triheptanoin (UX007) in patients with long-chain fatty acid oxidation disorders: Results from an open-label, long-term extension study. J Inherit Metab Dis. 2021;44:253-263. [PMC free article: PMC7891391] [PubMed: 32885845]

  (Among 75 patients with LC-FAOD enrolled in a 24-week controlled trial of triheptanoin vs MCT and then into a long term, open label study, the annualized rate of major clinical events [rhabdomyolysis, hypoglycemia, cardiomyopathy] decreased by 45% in those continued on triheptanoin and by 70% of those started de novo on the supplement, and while adverse event rates were high [99%], they were usually unrelated to therapy, and there were “no noteworthy changes in ...chemistry… laboratory values”).
• Striano P, Auvin S, Collins A, Horvath R, Scheffer IE, Tzadok M, Miller I, et al. A randomized, double-blind trial of triheptanoin for drug-resistant epilepsy in glucose transporter 1 deficiency syndrome. Epilepsia. 2022;63:1748-1760. [PMC free article: PMC9546029] [PubMed: 35441706]

  (Among 36 children, adolescents and adults with drug resistant seizures associated with glucose transporter 1 deficiency treated with triheptanoin or placebo for 8 weeks followed by open label triheptanoin for up to one year, there was a 13% reduction in seizures in triheptanoin treated subjects related to baseline and placebo, but adverse events were more frequent including diarrhea, abdominal pain, nausea and vomiting, while there were no treatment related serious adverse events and routine laboratory testing showed no “clinically significant changes”).
• Lasio MLD, Leshinski AC, Ducich NH, Flore LA, Lehman A, Shur N, Jayakar PB, et al. Clinical, biochemical and molecular characterization of 12 patients with pyruvate carboxylase deficiency treated with triheptanoin. Mol Genet Metab. 2023;139:107605. [PMC free article: PMC10330474] [PubMed: 37207470]

  (Among 12 subjects with pyruvate carboxylase deficiency treated with triheptanoin for variable periods [6 days to 7 years], there was considerable variability in clinical responses [lactate and amino acid levels, quality of life scores] but it was “found to be safe and with no serious adverse events”, although dose adjustments were sometimes needed for gastrointestinal intolerance).
• Vockley J, Burton BK, Berry G, Longo N, Phillips J, Sanchez-Valle A, Chapman KA, et al. Triheptanoin for the treatment of long-chain fatty acid oxidation disorders: Final results of an open-label, long-term extension study. J Inherit Metab Dis. 2023;46:943-955. [PubMed: 37276053]

  (In a final report of long term [3-4 years], open label therapy with triheptanoin for LC-FAODs, the overall adverse event rate was 97% and serious adverse event rate 75%, but most adverse events were related to the underlying disease and there were no liver related serious adverse events and no mention of ALT elevations).
• De Giorgis V, Bhatia KP, Boespflug-Tanguy O, Gras D, Marina AD, Desurkar A, Toledo M, et al. Triheptanoin did not show benefit versus placebo for the treatment of paroxysmal movement disorders in glut1 deficiency syndrome: results of a randomized phase 3 study. Mov Disord. 2024 May 9. Epub ahead of print. [PubMed: 38725190]

  (Among 43 patients with paroxysmal movement disorders due to Glut1 deficiency syndrome treated with triheptanoin or placebo for 10 weeks, there were no differences in rates of disabling movement events or in adverse event rates [93% vs 81%], which were mostly diarrhea, nausea and vomiting and abdominal pain while serious adverse events were uncommon and unrelated; no mention of ALT elevations or hepatotoxicity).