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Adipose Tissue_Appetite_and Obesity

SUN-689 - Efficacy and Safety of Resuming Diazoxide Choline Extended-Release (DCCR) after 16-week Randomized Withdrawal in Prader-Willi Syndrome (PWS) (Study C614)

Sunday, June 14, 2026
9:00 AM - 4:00 PM CT
Disclosure(s):
Ashley H. Shoemaker, MD, MSCI: .NovoNordisk: Clinical Trial Investigator (); Aardvark Therapeutics: Clinical Trial Investigator (); Eli Lilly & Company: Contracted Research (Principal Investigators must provide information, even if received by the institution) (); Rhythm Pharmaceuticals: Advisory Board (), Clinical Trial Investigator (), Consultant (), Employee (any industry) (); Soleno Therapeutics: Clinical Trial Investigator (), Consultant ()


Background: Prader-Willi Syndrome (PWS) is a rare genetic neurobehavioral-metabolic disorder characterized by pediatric-onset hyperphagia, a chronic, life-threatening condition that leads to reduced life expectancy with a median age of death at 23 years. Diazoxide choline extended-release (DCCR) is approved in the United States as VYKAT™ XR an oral, once-daily treatment for adults and children 4 years and older with PWS who have hyperphagia. The objective of this study was to evaluate the efficacy and safety of resuming DCCR after randomized withdrawal in PWS.

Methods: We assessed if resuming DCCR improved hyperphagia by the Hyperphagia for Clinical Trials questionnaire (HQ-CT) and PWS behaviors by the PWS Profile questionnaire (PWSP) over 2 years in 76 participants who previously completed 16 weeks of randomized withdrawal and 1 participant who had discontinued DCCR for 16 weeks. Changes in body mass index (BMI) were also assessed, as was long-term safety and tolerability.

Results: At C614 Baseline, mean (SD) age was 15.3 (4.63) years, 55.8% were female. HQ-CT Total Score was 15.4 (7.8) and 11.9 (7.9), mean (SD) for participants who restarted DCCR after placebo or remained on DCCR, respectively. Participants who restarted DCCR showed marked improvements in HQ-CT Total Score by 13 weeks (mean [SD], -4.5 [6.3]) that further improved by 26 weeks and 2 years (-5.5 [7.1] and -6.3 [8.4], respectively). Participants remaining on DCCR showed smaller but continued improvements after 13 weeks (-2.7 [6.9]) that were sustained at 26 weeks and 2 years (-3.3 [5.7] and -3.1 [8.0], respectively). Nonsignificant improvements in PWSP domain scores were seen at 13 and 26 weeks, with improvements in all 6 domains at 2 years in participants who restarted DCCR (mean [SD], aggression,-1.6 [3.8]; compulsivity, -2.2 [3.9]; rigidity/irritability, -1.1 [4.4]; anxiety, -2.2 [3.9]; disordered thinking, -0.6 [1.8]; and depression, -0.6 [2.1]). Mean Baseline BMI was 26.0 and 28.9 kg/m2 for participants restarting and remaining on DCCR, respectively, and remained relatively stable at 2 years, (27.2 and 29.1 kg/m2, respectively). Adverse events (AEs) were reported in 92.2% of participants. No deaths occurred and only 2/77 participants withdrew due to an AE. Treatment-related AEs occurring in ≥5% of participants included peripheral edema, hyperglycemia, increased blood glucose, increased glycosylated hemoglobin, and hypertrichosis. Serious AEs and Grade 3 AEs occurred in 8/77 participants and 9/77 participants, respectively.

Conclusion: In study C614, resuming DCCR for 2 years after 16-week randomized withdrawal was associated with improvements in both hyperphagia and behavioral symptoms characteristic of PWS. BMI remained relatively stable. Long-term DCCR treatment was generally well-tolerated with an AE profile consistent with that observed in previous clinical trials of DCCR in PWS.

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