Impact of UX007 and Dietary Management on Major Clinical Events in a 78-Week Single-arm Open-label Phase 2 LC-FAOD Study

Authors: Jerry Vockley, MD, PhD1; Nicola Longo, MD2; Megan Madden, MS, RD3; Lauren Dwyer MPH, RD3; Yunming Mu, PhD3; Chao-Yin Chen, PhD3; Jason Cataldo, DO3

1 University of Pittsburgh, Pittsburgh, PA, USA; 2 University of Utah, Salt Lake City, UT, USA; 3 Ultragenyx Pharmaceutical Inc., Novato, CA, USA

Corresponding Author: Jerry Vockley, MD, PhD, University of Pittsburgh, Pittsburgh, PA, USA

Corresponding Author contact information:;  (412) 692-7746

Background: LC-FAOD are autosomal recessive disorders caused by defects in mitochondrial fatty acid oxidation enzymes. UX007, a pharmaceutical grade, purified seven-carbon medium-chain triglyceride (MCT), is being investigated for treatment of LC-FAOD. A single-arm, Phase 2 study was conducted to prospectively evaluate safety and efficacy of 78 weeks of UX007 treatment in 29 pediatric and adult subjects with severe LC-FAOD, compared with a retrospective pre-UX007 period  during which subjects were optimally managed under current dietary guidelines by metabolic clinics.

Methods: Dietary reports were collected to examine the relationship between diet, UX007, and their impact on major clinical events (ie, rhabdomyolysis, hypoglycemia, and cardiomyopathy).

Results: Subjects followed standard FAOD diet recommendations during pre-UX007 period, usually including a source of MCT. For treatment period, subjects switched from MCT to UX007 with a targeted dose of 25-35% of daily caloric intake. Subjects received mean 17.4% daily caloric intake from MCT prior to entering the study and per protocol, received and overall tolerated mean 27.5% daily caloric intake from UX007 during the study, while protein, long-chain fat, and carbohydrates remained relatively consistent. Total daily caloric intake modestly increased from ~62 to 72 kcals/kg driven by energy requirements for growth and activity level. Following 78 weeks of UX007 treatment, the mean annualized major clinical events rate decreased from 1.69 to 0.88 events/year (48.1% reduction, p=0.021), and a 50% reduction in median event rate from 1.33 to 0.66. The mean annualized major clinical events duration rate decreased from 5.96 to 2.96 days/year (50.3% reduction, p=0.028), and there was a 77% reduction in median hospital days from 5.33 to 1.24.

Discussion: Dosed at 25-35% daily caloric intake, UX007 demonstrated significant reduction in major clinical events compared with subjects’ prior treatment regimens. It is important to consider that the transition from MCT to UX007 and UX007’s anaplerotic effect may have also contributed to the improvement.

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