ESPE2024 Free Communications Fat, Metabolism and Obesity 1 (6 abstracts)
Relaxation of Food Control Parameters Based on Improvements in the Food Safe Zone Questionnaire Occurs with Reduction of Hyperphagia in Clinical Trials of Diazoxide Choline Extended Release (DCCR) in Participants with Prader-Willi Syndrome
Nicola Bridges 1 , Evelien Gevers 2,3 , Jack Yanovski 4 , Parisa Salehi 5 , Ashley Hall Shoemaker 6 , Jennifer Abuzzahab 7 , Kathryn Obrynba 8 , Amy Fleischman 9 , David Stevenson 10 , John Wilding 11 , Verghese Mathew 12 , David Viskochil 13 , Eric Felner 14 , Shawn E. McCandless 15 , Lynne Bird 16,17 , Melissa Lah 18 , Elizabeth Littlejohn 19 , Heidi Shea 20 , Anthony Holland 21 , Anthony Goldstone 22 , Timothy Barrett 23 , Laura Konczal 24 , Poonam Dharmaraj 25 , Urmi Das 25 , Moris Angulo 26 , Virginia Kimonis 27 , Mohomad Guftar Shaikh 28 , Jorge Mejia-Corletto 29 , Kristen Yen 30 , Raj Gandhi 30 , Shaila Ballal 30 , Patricia Hirano 30 , Neil Cowen 30 , Anish Bhatnagar 30 , Michael Huang 30 , Merlin Butler 31 & Jennifer Miller 32
1Chelsea and Westminster Hospital NHS Trust, London, United Kingdom. 2Queen Mary University of London, Barts and The London Medical School, Wiliam Harvey Research Institute, Centre for Endocrinology, London, United Kingdom. 3Barts Health NHS Trust, Royal London Hospital, London, United Kingdom. 4National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. 5Seattle Children's, Seattle, WA, USA. 6Vanderbilt University Medical Center, Nashville, TN, USA. 7Children's Minnesota, St. Paul, MN, USA. 8Nationwide Children’s Hospital, Columbus, OH, USA. 9Boston Children's Hospital, Boston, MA, USA. 10Stanford University, Stanford, CA, USA. 11Aintree University Hospital, Liverpool, United Kingdom. 12Hull University Teaching Hospitals NHS Trust, Hull, United Kingdom. 13University of Utah, Salt Lake City, UT, USA. 14Emory University School of Medicine, Atlanta, GA, USA. 15University of Colorado, Children’s Hospital Colorado, Aurora, CO, USA. 16University of California San Diego, San Diego, CA, USA. 17Rady Children’s Hospital, San Diego, CA, USA. 18Indiana University School of Medicine, Indianapolis, IN, USA. 19University of Michigan Health-Sparrow, Lansing, MI, USA. 20Endocrine Associates of Dallas, Plano, TX, USA. 21University of Cambridge, Cambridge, United Kingdom. 22Imperial College London Healthcare NHS Trust, London, United Kingdom. 23University of Birmingham, Birmingham Women’s and Children’s Hospital NHS Trust, Birmingham, United Kingdom. 24University Hospitals of Cleveland, Cleveland, OH, USA. 25Alder Hey Children’s NHS Foundation Trust, Liverpool, United Kingdom. 26Good Samaritan Hospital Pediatrics, Babylon, NY, USA. 27University of California, Irvine Medical Center, Irvine, CA, USA. 28Royal Hospital for Children, Glasgow, United Kingdom. 29New York University Langone Hospital, Garden City, NY, USA. 30Soleno Therapeutics, Inc., Redwood City, CA, USA. 31Kansas University Medical Center, Kansas City, KS, USA. 32University of Florida, Gainesville, FL, USA
Background: Prader-Willi syndrome (PWS) is a rare genetic neurobehavioral-metabolic disorder characterized by hyperphagia and behavioral/psychological complications. With no approved therapies to treat hyperphagia, disease management requires strict dietary and environmental controls to restrict access to food. DCCR is an oral, once-daily medication currently under development for the treatment of PWS.
Objective: The objective was to analyze food controls via the Food Safe Zone (FSZ) Questionnaire across several Phase 3 PWS studies in relation to changes in the Hyperphagia Questionnaire for Clinical Trials (HQ-CT) Total Scores.
Methods: Data were included from: Study C601, a 13-week double-blind, placebo-controlled study; Study C602-OLE, a long-term open-label extension period following Study C601 (which included data from DCCR-treated participants in Study C601); Study C602-RWP, a 16-week double-blind, placebo-controlled randomized withdrawal period following Study C602-OLE; and Study C610, an externally-controlled study comparing Study C602-OLE to the PATH for PWS registry (PATH). HQ-CT Total Scores and FSZ domains were analyzed across each study.
Results: 125 participants ≥4 years of age with genetically confirmed PWS received DCCR in the Phase 3 program. In Study C610, significant reductions (P <0.05) were observed for DCCR versus Placebo for the FSZ domains “Restrict food access” and “Food supervision at home” at 26 and 52 weeks, and “Food supervision with others” at Week 26. In Study C602-OLE, significant reductions (P <0.05) in 4 of 5 domains (“Restrict food access”, “Check for food”, “Food supervision with others”, and “Food supervision at home”) relative to Baseline were observed at all timepoints from Weeks 26 through 156. In Study C601, a significant decrease in HQ-CT Total Scores was observed in DCCR versus Placebo prior to the onset of COVID-19 (P = 0.0369). In Study C602-OLE, HQ-CT Total Score changes from Baseline were significant (P <0.0001) and meaningful (-8.8 to -11.6 points) from Weeks 26 through 156. Comparison to the PATH cohort (Study C610) also demonstrated significance (P <0.001) at Weeks 26 and 52. Following randomized withdrawal (Study C602-RWP) of study drug after 2-4 years of exposure, the HQ-CT Total Score worsened significantly in Placebo as compared to DCCR (P = 0.0022). Overall, across several Phase 3 studies, hyperphagia was significantly improved despite reductions in food control parameters.
Conclusions: DCCR administration to participants with PWS resulted in durable, meaningful, and statistically significant reductions in hyperphagia in the Phase 3 studies even as food controls were relaxed, easing the burden of caring for patients with PWS.
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