Interim results from an open-label, long-term extension study to evaluate the safety and efficacy of triheptanoin (UX007) in LC-FAOD

Presented By:

Jerry Vockley, MD, PhD1; Barbara Burton, MD2; Gerard Berry, MD3; Nicola Longo, MD, PhD4; John A. Phillips, MD5; Amarilis Sanchez-Valle, MD6; Kimberly Chapman, MD7; Pranoot Tanpaiboon, MD7; Stephanie Grunewald, MD, PhD8; Elaine Murphy, MD9; Alexandra Bowden, PhD10; Yunming Mu, PhD10; Jason Cataldo, DO10

1University of Pittsburgh, Pittsburgh, PA, USA; 2Ann & Robert H. Lurie Children’s Hospital, Chicago, Illinois, USA; 3Boston Children’s Hospital, Boston, MA, USA; 4University of Utah, Salt Lake City, UT, USA; 5Vanderbilt University Medical Center, Nashville, TN, USA; 6USF Health, Morsani College of Medicine, Tampa, FL, USA; 7Children’s National Health System, Washington DC, USA; 8Great Ormond St, UCL Institute of Child Health, London, UK; 9National Hosp for Neurology & Neurosurgery, London, UK; 10Ultragenyx Pharmaceutical Inc., Novato, CA, USA

Background: Long-chain fatty acid oxidation disorders (LC-FAOD) are autosomal recessive conditions that impair conversion of long-chain fatty acids into energy, resulting in major clinical events (MCEs). Triheptanoin (trihep) is a highly purified, 7-carbon chain triglyceride being investigated for LC-FAOD treatment.

Methods: An open-label, long-term extension study (NCT02214160) is evaluating safety and efficacy of trihep in patients (pts) with LC-FAOD who participated in prior clinical trials or investigator-sponsored trials (ISTs) or expanded access; pts not previously treated with trihep also are enrolled.

Results: In total, 75 pts enrolled as of June 1, 2018; 24 rolled over from the Phase 2 study. Prior to trihep, these 24 pts had a median annualized event rate (AER) of 1.5 events/yr. Following an additional 78 wks of trihep (≥3 yrs of total treatment), pts had a 67% reduction in median AER (0.5 events/yr, overall; 0.7 events/yr, Phase 2; 0 events/yr, extension). Twenty pts not previously treated with trihep had a pre-treatment median AER of 2.3 events/yr. In these pts, a median of 63 wks of trihep treatment resulted in a 70% reduction in median AER (0.7 events/yr), consistent with results seen in the 24 rollover pts. In 31 pts from ISTs or expanded access, pre-treatment data were not available for comparison. The most common related adverse events (AEs) among all 75 pts were diarrhea, abdominal pain/discomfort, and vomiting, with most mild to moderate in severity. Three pts had AEs classified as serious due to hospitalization (diverticulitis, ileus, rhabdomyolysis) considered possibly related to drug by the investigator; all resolved. Two pts had AEs leading to death; neither was deemed related to drug. Most pts (87%) are continuing treatment.

Discussion: Trihep showed sustained clinical benefit in reducing the rate and duration of MCEs in 2 distinct patient cohorts. Additionally, safety was consistent with previous observations during this long-term treatment.

Disclosures:

JV, BB, GB, NL, JP, ASV, KC, PT, SG, and EM are clinical investigators for this study sponsored by Ultragenyx Pharmaceutical Inc. YM and JC are employees of Ultragenyx Pharmaceutical Inc. AB is a former employee of Ultragenyx Pharmaceutical Inc.

Corresponding author contact information:

Jerry Vockley, M.D., Ph.D.

Office: (412) 692-7746

Cell: (412) 973-5971

e-mail: gerard.vockley@chp.edu