Diazoxide choline
Diazoxide choline controlled-release (DCCR) is currently under review by the US Food and Drug Administration (FDA) for management of hyperphagia. DCCR is a K-ATP channel agonist, which may reduce hyperphagia in PWS by down-regulating insulin secretion from pancreatic beta cells and secretion of neuropeptide Y, and activating K-ATP channels in adipose tissue. A double blind, placebo-controlled study that compared DCCR to placebo did not meet its primary endpoint of change from baseline in hyperphagia over a 13 week period, measured by hyperphagia questionnaire scores.[61]Miller JL, Gevers E, Bridges N, et al. Diazoxide choline extended-release tablet in people with Prader-Willi syndrome: a double-blind, placebo-controlled trial. J Clin Endocrinol Metab. 2023 Jan 14;dgad014.
https://academic.oup.com/jcem/advance-article/doi/10.1210/clinem/dgad014/6987298
http://www.ncbi.nlm.nih.gov/pubmed/36639249?tool=bestpractice.com
However, it did show significant improvement in hyperphagia for patients with severe hyperphagia. There was also significant improvement in physician-assessed Clinical Global Impression of Improvement score and reduction of body fat mass.[61]Miller JL, Gevers E, Bridges N, et al. Diazoxide choline extended-release tablet in people with Prader-Willi syndrome: a double-blind, placebo-controlled trial. J Clin Endocrinol Metab. 2023 Jan 14;dgad014.
https://academic.oup.com/jcem/advance-article/doi/10.1210/clinem/dgad014/6987298
http://www.ncbi.nlm.nih.gov/pubmed/36639249?tool=bestpractice.com
Data from an ongoing trial where patients receive DCCR for 6 months have shown continued improvement in hyperphagia scores after the initial 13 weeks of treatment, as well as improvements in body composition (i.e., improved lean body mass and lean/fat mass ratio) and many of the characteristic behavioural issues in PWS (e.g., repetitive questioning, anxiety, compulsive behaviours, skin picking).[61]Miller JL, Gevers E, Bridges N, et al. Diazoxide choline extended-release tablet in people with Prader-Willi syndrome: a double-blind, placebo-controlled trial. J Clin Endocrinol Metab. 2023 Jan 14;dgad014.
https://academic.oup.com/jcem/advance-article/doi/10.1210/clinem/dgad014/6987298
http://www.ncbi.nlm.nih.gov/pubmed/36639249?tool=bestpractice.com
Other drugs
Other drugs being investigated for use in patients with PWS include the synthetic oxytocin analogue carbetocin for management of hyperphagia and pitolisant (a H3 antagonist/inverse agonist) for treatment of excessive daytime somnolence, narcolepsy, and cataplexy.[62]Dykens EM, Miller J, Angulo M, et al. Intranasal carbetocin reduces hyperphagia in individuals with Prader-Willi syndrome. JCI Insight. 2018 Jun 21;3(12):e98333.
https://insight.jci.org/articles/view/98333
http://www.ncbi.nlm.nih.gov/pubmed/29925684?tool=bestpractice.com
[63]Ryman D, Deal CL. Topline results of the CARE-PWS phase 3 study: intranasal carbetocin improves hyperphagia and anxiety and distress symptoms in Prader-Willi syndrome (PWS) J Endocr Soc. 2021 Apr-May; 5(suppl 1):A689.
https://academic.oup.com/jes/article/5/Supplement_1/A689/6241772
[64]ClinicalTrials.gov. A phase 2 study to evaluate the safety and efficacy of pitolisant in patients with Prader-Willi syndrome, followed by an open label extension. ClinicalTrials.gov Identifier: NCT04257929. May 2023 [internet publication].
https://clinicaltrials.gov/ct2/show/NCT04257929