ECE2022 Eposter Presentations Diabetes, Obesity, Metabolism and Nutrition (318 abstracts)
Long-term safety of diazoxide choline extended-release (DCCR) tablets in patients with prader-willi syndrome
Evelien Gevers 1 , Jennifer Miller 2 , Merlin Butler 3 , Nicola Bridges 4 , Tony Goldstone 5 , Kathryn Obrynba 6 , Parisa Salehi 7 , Eric Felner 8 , Lynne Bird 9 , Ashley Shoemaker 10 , Laura Konczal 11 , Melissa Lah 12 , Jack Yanovski 13 , Moris Angulo 14 , Jorge Mejia-Corletto 15 , David Stevenson 16 , John Wilding 17 , Jennifer Abuzzahab 18 , Guftar Shaikh 19 , David Viskochil 20 , Verghese Mathew 21 , Kristen Yen 22 , Michael Woloschak 22 & Anish Bhatnagar 22
1Queen Mary University of London Barts Health NHS Trust, London, United Kingdom; 2University of Florida Gainesville, Gainesville, United States;3Kansas University Medical Center, Kansas City, KS, United States; 4Chelsea and Westminster Hospital, London, United Kingdom; 5Hammersmith Hospital, London, United Kingdom; 6The Research Institute at Nationwide Children’s Hospital, Columbus, United States; 7Seattle Children’s, Seattle, United States; 8Emory Children’s Center, Atlanta, United States; 9Rady Children’s Hospital of San Diego, San Diego, United States;10Vanderbilt University, Nashville, United States; 11UH Cleveland Medical Center, Cleveland, United States; 12Indiana University School of Medicine, Indianapolis, United States; 13National Institutes of Health, Bethesda, United States; 14NYU Winthrop Hospital, Mineola, United States; 15NYU Langone Hospital-Long Island, Pediatrics, Division of Pediatric Endocrinology, Mineola,; 16Stanford University, Palo Alto, United States; 17Aintree University Hospital NHS Foundation Trust, Liverpool, United Kingdom; 18Children’s Minnesota, Saint Paul, United States; 19Royal Hospital for Children, Glasgow, Paediatric Endocrinology, Glasgow, United Kingdom;20The University of Utah, Salt Lake City, United States; 21Hull and East Yorkshire Hospitals NHS Trust, Hull, United Kingdom; 22Soleno Therapeutics, Inc., Redwood City, United States
Background: Prader-Willi syndrome (PWS), a rare genetic neurobehavioral-metabolic condition, is characterized by hyperphagia, accumulation of excess fat, hypotonia, and behavioral/psychological complications. There are no currently approved medications to treat hyperphagia in patients with PWS; DCCR is under development as a treatment for PWS.
Objectives and Methods: The objective was to evaluate long-term safety of DCCR in individuals with PWS. 125 participants with genetically-confirmed PWS ≥4 years old with hyperphagia were treated with oral daily DCCR in multi-center studies conducted at 29 sites in the US and the UK: a 13-week, Phase 3, double-blind, placebo-controlled study (DESTINY PWS) and its long-term, open-label extension study (to 52 weeks and beyond). The target DCCR dose was ≥3.3 mg/kg (optimal dose 4.2 - 5.8 mg/kg). 103 patients received DCCR for 52 weeks and 54 patients received DCCR for at least 78 weeks.
Results: Overall, DCCR was well tolerated with the majority of adverse events (AEs), (77.6%) having grade 1 or 2 severity. Treatment-emergent adverse events (TEAEs) occurred in 98.4% of participants. Drug related TEAEs occurred in 80.0% of participants. Twenty participants experienced serious adverse events (SAEs), for which only two participants were considered drug-related (one patient with peripheral/pulmonary edema and another with fluid retention). There were no SAEs leading to death. The most common TEAEs were hypertrichosis (61.6%), peripheral edema (34.4%), and hyperglycemia (22.4%). TEAEs infrequently resulted in discontinuation of study drug (7.2% of participants). These results are consistent with the observed safety profile of DCCR from prior studies. Consistent with the expected AE of hyperglycemia, fasting glucose rose through Week 26 (mean change from baseline ± SD mmol/l = 0.35±0.81) and returned nearly to baseline by 15 months of treatment (0.11±0.61). HbA1c followed a similar pattern, increasing at 26 weeks and returning nearly to baseline by 15 months. In participants experiencing hyperglycemia, the AE resolved with continued treatment in about half of cases. About 90% of peripheral edema cases resolved while treatment continued, requiring infrequent dose adjustment (7%) or the need for diuretic treatment (3%). Most cases of hypertrichosis (>80%) were mild and only in one instance led to discontinuation. About 35% of cases of hypertrichosis were resolved/resolving at Week 52.
Conclusions: DCCR was ell tolerated beyond 52 weeks of administration. The most common treatment-emergent adverse events were expected based on prior studies of DCCR. These included hypertrichosis, peripheral edema and hyperglycemia, which were typically mild and resolved without treatment in most cases.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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