Abstract
Long-chain fatty acid oxidation disorders (LC-FAOD) are rare disorders characterized by acute crises of energy metabolism and severe energy deficiency that may present with cardiomyopathy, hypoglycemia, and/or rhabdomyolysis, which can lead to frequent hospitalizations and early death. An open-label Phase 2 study evaluated the efficacy of UX007, an investigational odd-carbon medium-chain triglyceride, in 29 subjects with severe LC-FAOD. UX007 was administered over 78 weeks at a target dose of 25–35% total daily caloric intake (mean 27.5%). The frequency and duration of major clinical events (hospitalizations, emergency room visits, and emergency home interventions due to rhabdomyolysis, hypoglycemia, and cardiomyopathy) occurring during 78 weeks of UX007 treatment was compared with the frequency and duration of events captured retrospectively from medical records for 78 weeks before UX007 initiation. The mean annualized event rates decreased from 1.69 to 0.88 events/year following UX007 initiation (p = 0.021; 48.1% reduction). The mean annualized duration rate decreased from 5.96 to 2.96 days/year (p = 0.028; 50.3% reduction). Hospitalizations due to rhabdomyolysis, the most common event, decreased from 1.03 to 0.63 events/year (p = 0.104; 38.7% reduction). Initiation of UX007 eliminated hypoglycemia events leading to hospitalization (from 11 pre-UX007 hospitalizations, 0.30 events/year vs. 0; p = 0.067) and intensive care unit (ICU) care (from 2 pre-UX007 ICU admissions, 0.05 events/year vs. 0; p = 0.161) and reduced cardiomyopathy events (3 events vs. 1 event; 0.07 to 0.02 events/year; 69.7% decrease). The majority of treatment-related adverse events (AEs) were mild to moderate gastrointestinal symptoms, including diarrhea, vomiting, and abdominal or gastrointestinal pain, which can be managed with smaller, frequent doses mixed with food.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 169-177 |
| Number of pages | 9 |
| Journal | Journal of inherited metabolic disease |
| Volume | 42 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2019 |
Funding
The Phase 2 study (UX007-CL201) was sponsored by Ultra-genyx Pharmaceutical Inc. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. JV is supported in part by NIH grant R01 DK78755. The authors thank Elizabeth Little, PhD, of Ultragenyx Pharmaceutical Inc. for providing writing assistance. The authors thank the clinical research coordinators and dietitians at the UX007-CL201 research centers: Clare Edano, Charlotte Dodsworth, Rachel Katz, Amanda Kasper, Dylan Fogel, Heather Bausell, Maryam Naziri, Leslie Stiles (Ann & Robert H. Lurie Children's Hospital of Chicago); Vera Anastasoaie, Kyla Almeida, Sophia Kon, Kalin Charette, Fran Rohr, Ann Wessel (Boston Children's Hospital); Elizabeth McCracken, Jennifer Baker, Maggie Hufton, Angela Leshinski, Danielle Black, Nancy Perrott (Children's Hospital of Pittsburgh); Carrie Bailey, Jenny Billy, Sarah Couchon, Mary Jane Dunkley, Kyle Berg, Sharon Ernst, Krista Viau, Chelsey Clegg, Maria Ralph (University of Utah); Natalie Nicole Owen, Leeanna Melton, Amanda Bawcom, Morgan Mills, Gina Wey, Ellen Strickler (Vanderbilt University Medical Center); Denise Casey, Donna O'Steen (University of South Florida Health); Katie Crosby, Lindsay Kehoe, Matthew Rasberry, Erin MacLeod (Children's National Medical Center); Laura Lee, Helen Ashton, Stephanie Tingley, Alice Roberts, Danielle Miller, Marjorie Dixon, James Twigg (Great Ormond Street Hospital); Rachel Carruthers, Kit Kaalund-Hansen, Daniela Velinova (Charles Dent Metabolic Unit). The authors would also like to acknowledge the efforts of Devon Jackson, Joyce Nussbaum, and Elisa Yoritomi (Ultragenyx Pharmaceutical Inc.). The Phase 2 study (UX007-CL201) was sponsored by Ultragenyx Pharmaceutical Inc. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. JV is supported in part by NIH grant R01 DK78755. The authors thank Elizabeth Little, PhD, of Ultragenyx Pharmaceutical Inc. for providing writing assistance. The authors thank the clinical research coordinators and dietitians at the UX007-CL201 research centers: Clare Edano, Charlotte Dodsworth, Rachel Katz, Amanda Kasper, Dylan Fogel, Heather Bausell, Maryam Naziri, Leslie Stiles (Ann & Robert H. Lurie Children's Hospital of Chicago); Vera Anastasoaie, Kyla Almeida, Sophia Kon, Kalin Charette, Fran Rohr, Ann Wessel (Boston Children's Hospital); Elizabeth McCracken, Jennifer Baker, Maggie Hufton, Angela Leshinski, Danielle Black, Nancy Perrott (Children's Hospital of Pittsburgh); Carrie Bailey, Jenny Billy, Sarah Couchon, Mary Jane Dunkley, Kyle Berg, Sharon Ernst, Krista Viau, Chelsey Clegg, Maria Ralph (University of Utah); Natalie Nicole Owen, Leeanna Melton, Amanda Bawcom, Morgan Mills, Gina Wey, Ellen Strickler (Vanderbilt University Medical Center); Denise Casey, Donna O'Steen (University of South Florida Health); Katie Crosby, Lindsay Kehoe, Matthew Rasberry, Erin MacLeod (Children's National Medical Center); Laura Lee, Helen Ashton, Stephanie Tingley, Alice Roberts, Danielle Miller, Marjorie Dixon, James Twigg (Great Ormond Street Hospital); Rachel Carruthers, Kit Kaalund-Hansen, Daniela Velinova (Charles Dent Metabolic Unit). The authors would also like to acknowledge the efforts of Devon Jackson, Joyce Nussbaum, and Elisa Yoritomi (Ultragenyx Pharmaceutical Inc.).
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)