Diazoxide choline data show durable hyperphagia gains in Prader-Willi syndrome

New late-breaking data presented at ENDO 2026 suggest that patients with Prader-Willi syndrome (PWS) who restarted diazoxide choline extended-release tablets (VYKAT XR) after a randomized withdrawal period regained improvements in hyperphagia, with effects reported through 2 years of follow-up, according to Neurocrine Biosciences and Soleno Therapeutics.¹

“These compelling data further reinforce our confidence in VYKAT XR as a safe and effective long-term treatment for hyperphagia in individuals four years of age and older living with Prader-Willi syndrome,” Sanjay Keswani, MD, chief medical officer of Neurocrine Biosciences, said in the company announcement.¹ The findings are clinically relevant because hyperphagia is a central and difficult-to-manage feature of PWS, often requiring continuous environmental controls, caregiver supervision, and multidisciplinary care.

The data come from Study C614, an open-label long-term extension study that followed a sequential phase 3 development program. That program included a 13-week randomized, double-blind, parallel-arm trial, known as C601, comparing VYKAT XR with placebo in patients aged 4 years or older with genetically confirmed PWS and hyperphagia; an open-label extension study, C602 OLE; a 16-week double-blind, placebo-controlled randomized withdrawal period; and the C614 extension.

C614 enrolled 77 participants with a mean age of 15.3 years; 55.8% were female. Investigators assessed whether participants assigned to placebo during the randomized withdrawal period could recover prior benefit after restarting VYKAT XR and whether those who remained on continuous therapy maintained treatment effect. Hyperphagia was measured with the Hyperphagia Questionnaire for Clinical Trials (HQ-CT), and PWS-related behavioral symptoms were measured with the PWS Profile questionnaire. Body mass index and long-term safety were also assessed.

Among participants who restarted VYKAT XR after placebo withdrawal, the mean HQ-CT Total Score improved by week 13, with a mean (SD) change of –4.5 (6.3). Additional improvement was reported at week 26 and 2 years, with changes of –5.5 (7.1) and –6.3 (8.4), respectively. Participants who remained on continuous VYKAT XR had smaller mean improvements at week 13, –2.7 (6.9), which were sustained at week 26 and 2 years, –3.3 (5.7) and –3.1 (8.0), respectively. The company also reported improvements across all 6 PWS Profile behavioral domains at 2 years among those who restarted therapy, while BMI remained relatively stable.

Separate ENDO 2026 analyses compared treated participants from the VYKAT XR program with participants in the PATH for PWS Natural History Study. In an HQ-CT analysis, 125 VYKAT XR–treated participants from C601 and C602-OLE were compared with 229 natural history controls. Reported adjusted treatment differences favoring VYKAT XR were 6.2 points at year 1, 6.5 points at year 2, and 6.2 points at year 3, with P < .0001 at all evaluated time points. A behavioral analysis comparing 105 treated participants with 182 PATH controls found statistically significant differences across all 6 behavioral domains through 3 years, favoring VYKAT XR.

PWS is a rare genetic neurodevelopmental disorder caused by a lack of expression of paternally inherited genes in the chromosome 15q11-q13 region. Clinical manifestations can include neonatal hypotonia, developmental delay, endocrine abnormalities, behavioral dysregulation, obesity risk, and hyperphagia, which typically emerges in childhood and can create substantial safety concerns for families and caregivers.³

VYKAT XR was approved by the US Food and Drug Administration on March 26, 2025, for treatment of hyperphagia in adults and pediatric patients aged 4 years or older with PWS.^1,2 Diazoxide choline is an extended-release formulation of diazoxide. The precise mechanism by which it reduces hyperphagia in PWS is not fully established, but diazoxide is associated with activation of ATP-sensitive potassium channels and effects on insulin secretion.²

For clinicians, the new data provide additional follow-up after withdrawal and retreatment, but interpretation should remain cautious. C614 was open-label, and the long-term comparisons with PATH used external natural history controls rather than random assignment. These designs can help characterize durability and safety but cannot fully control for selection bias, differences in baseline characteristics, or changes in supportive care.

Safety considerations remain central in pediatric and adolescent use. VYKAT XR is contraindicated in patients with known hypersensitivity to diazoxide, components of the product, or thiazides. The prescribing information warns about hyperglycemia, including diabetic ketoacidosis, and recommends baseline and ongoing monitoring of fasting plasma glucose or fasting blood glucose and hemoglobin A1c. Edema and fluid overload have also been reported, and the drug has not been studied in patients with compromised cardiac reserve. The most common adverse reactions reported at an incidence of at least 10% and at least 2% greater than placebo were hypertrichosis, edema, hyperglycemia, and rash.²

References

1. Neurocrine Biosciences, Inc. Soleno Therapeutics presents new VYKAT XR (diazoxide choline) data at ENDO 2026 demonstrating meaningful and durable improvements in hyperphagia and behavioral symptoms in Prader-Willi syndrome following randomized withdrawal period. PR Newswire. June 15, 2026. Accessed June 16, 2026. https://www.prnewswire.com/news-releases/soleno-therapeutics-presents-new-vykat-xr-diazoxide-choline-data-at-endo-2026-demonstrating-meaningful-and-durable-improvements-in-hyperphagia-and-behavioral-symptoms-in-prader-willi-syndrome-following-randomized-withdrawal-per-302799792.html

2. VYKAT XR (diazoxide choline) extended-release tablets. Prescribing information. Soleno Therapeutics, Inc. Accessed June 16, 2026. https://www.vykatxr.com/prescribing-information.pdf

3. Cassidy SB, Schwartz S, Miller JL, Driscoll DJ. Prader-Willi syndrome. Genet Med. 2012;14(1):10-26. doi:10.1038/gim.0b013e31822bead0