The Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD) Disease Monitoring Program: An Evaluation of Initial Findings
Biochemical/Metabolic and Therapeutics
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Primary Categories:
- Clinical- Pediatric
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Secondary Categories:
- Clinical- Pediatric
Introduction:
Introduction: The long-chain fatty acid oxidation disorders (LC-FAOD) disease monitoring program (DMP) is a multinational, observational, long-term, retrospective and prospective study of pediatric and adult patients with LC-FAOD. LC-FAOD are a group of rare, autosomal-recessive disorders of fatty acid metabolism in the mitochondria. These disorders may manifest in infants, but also commonly present in older children or adults following periods of increased metabolic demand, including physiologic stress, fasting, and prolonged exercise. Disease presentation can be heterogeneous, unpredictable, and serious, including life-threatening episodes of rhabdomyolysis, hypoglycemia, and cardiomyopathy. Triheptanoin is an odd-carbon, medium-chain triglyceride approved for the treatment of LC-FAOD in the United States, Canada, Brazil, and Mexico.
Methods:
Methods: The LC-FAOD DMP is planned to collect safety and effectiveness data for triheptanoin and/or LC-FAOD natural history data for up to 10 years. Participants (N≈150 planned) are managed at the discretion of their treating providers. The primary objective is to assess the long-term safety, including pregnancy, infant, and lactation outcomes, of participants with LC-FAOD enrolled in the DMP. Secondary objectives are to 1) assess the long-term effectiveness of triheptanoin treatment on key LC-FAOD manifestations, including major clinical events (MCEs) of rhabdomyolysis, cardiomyopathy, and hypoglycemia, 2) investigate the dose-response relationship of triheptanoin and even-carbon medium-chain triglyceride oil on MCEs and at-home clinical events, and 3) assess the impact of triheptanoin on patient- and clinician-reported measures of disease severity and burden. Patients treated with triheptanoin receive the medication through commercial use or expanded access programs (EAP). Enrollment is ongoing. Major clinical events (MCEs) are defined as hospitalizations and emergency interventions for LC-FAOD, and deaths related to LC-FAOD.
Results:
Results: The first patient was enrolled on 30 November 2021. As of 28 February 2024, 56 pediatric (<18 years of age) and 27 adult (≥18 years of age) participants with LC-FAOD were enrolled. The median (min, max) age at enrollment was 12.0 (0.6, 71.0), with 44/83 (53%) male. Median (min, max) years of age at LC-FAOD diagnosis was 0.1 (0.1, 52.0) years. Fifty-three (64%) participants had ever received triheptanoin; of these, 33 participants completed the Year 1 visit. In 22 participants with baseline prescribed triheptanoin dose available, the percentage of daily caloric intake from triheptanion ranged from 5% to 35%, with a mean of 24.6%. In patients never treated with triheptanoin (n=30), the mean (SD) baseline total number of MCEs was 0.6 (0.9), comparable to the total triheptanoin group (n=53) with a mean (SD) baseline total number of MCEs of 0.7 (1.5).
Conclusion:
Conclusions: As of the data cutoff date for this analysis, baseline prescribed triheptanoin dose as a percentage of daily caloric intake ranged from 5% to 35%. MCE data are limited beyond the baseline visit for participants in all cohorts. Follow-up and enrollment are ongoing and additional timepoints and endpoints will be presented.
Introduction: The long-chain fatty acid oxidation disorders (LC-FAOD) disease monitoring program (DMP) is a multinational, observational, long-term, retrospective and prospective study of pediatric and adult patients with LC-FAOD. LC-FAOD are a group of rare, autosomal-recessive disorders of fatty acid metabolism in the mitochondria. These disorders may manifest in infants, but also commonly present in older children or adults following periods of increased metabolic demand, including physiologic stress, fasting, and prolonged exercise. Disease presentation can be heterogeneous, unpredictable, and serious, including life-threatening episodes of rhabdomyolysis, hypoglycemia, and cardiomyopathy. Triheptanoin is an odd-carbon, medium-chain triglyceride approved for the treatment of LC-FAOD in the United States, Canada, Brazil, and Mexico.
Methods:
Methods: The LC-FAOD DMP is planned to collect safety and effectiveness data for triheptanoin and/or LC-FAOD natural history data for up to 10 years. Participants (N≈150 planned) are managed at the discretion of their treating providers. The primary objective is to assess the long-term safety, including pregnancy, infant, and lactation outcomes, of participants with LC-FAOD enrolled in the DMP. Secondary objectives are to 1) assess the long-term effectiveness of triheptanoin treatment on key LC-FAOD manifestations, including major clinical events (MCEs) of rhabdomyolysis, cardiomyopathy, and hypoglycemia, 2) investigate the dose-response relationship of triheptanoin and even-carbon medium-chain triglyceride oil on MCEs and at-home clinical events, and 3) assess the impact of triheptanoin on patient- and clinician-reported measures of disease severity and burden. Patients treated with triheptanoin receive the medication through commercial use or expanded access programs (EAP). Enrollment is ongoing. Major clinical events (MCEs) are defined as hospitalizations and emergency interventions for LC-FAOD, and deaths related to LC-FAOD.
Results:
Results: The first patient was enrolled on 30 November 2021. As of 28 February 2024, 56 pediatric (<18 years of age) and 27 adult (≥18 years of age) participants with LC-FAOD were enrolled. The median (min, max) age at enrollment was 12.0 (0.6, 71.0), with 44/83 (53%) male. Median (min, max) years of age at LC-FAOD diagnosis was 0.1 (0.1, 52.0) years. Fifty-three (64%) participants had ever received triheptanoin; of these, 33 participants completed the Year 1 visit. In 22 participants with baseline prescribed triheptanoin dose available, the percentage of daily caloric intake from triheptanion ranged from 5% to 35%, with a mean of 24.6%. In patients never treated with triheptanoin (n=30), the mean (SD) baseline total number of MCEs was 0.6 (0.9), comparable to the total triheptanoin group (n=53) with a mean (SD) baseline total number of MCEs of 0.7 (1.5).
Conclusion:
Conclusions: As of the data cutoff date for this analysis, baseline prescribed triheptanoin dose as a percentage of daily caloric intake ranged from 5% to 35%. MCE data are limited beyond the baseline visit for participants in all cohorts. Follow-up and enrollment are ongoing and additional timepoints and endpoints will be presented.