By Marcin Miszkowski
2023 has been a significant year in the development of treatments to help manage some of the symptoms of Prader-Willi Syndrome.
In December 2022, findings from a Phase 3 trial for treatment showed that along with an exercise program, treatment with Liraglutide eased excessive hunger in children and adolescents with Prader-Willi Syndrome. Researchers wanted to measure the effectiveness of Liraglutide in children and adolescents with PWS, considering its reported benefits in regulating the appetite in adults. The study which was conducted across 20 clinical sites in a number of countries Show that lyra glue tied had no significant impact on body mass index or other body weight related parameters. However, hyperphagia drive scores significantly reduced in adolescents after 52 weeks receiving Liraglutide compared to those given a placebo. Some side effects were observed – most notably diarrhea and abdominal pain. There were no reports of suicidal thoughts and no participants scored 15 or higher in the Patient Health Questionnaire-9, a measure of depression. Liraglutide also appeared to have no impact on puberty development or growth rate. Moving forward, researchers are keen to investigate the apparent improvement in hyperphagia drive.
In June of this year, CSTI-500 showed positive outcomes from a Phase 1 clinical trial in dealing with symptoms of Prader-Willi Syndrome, paving the way for Phase 2 clinical testing. CSTI-500 has the potential to deal with two of the most significant symptoms of PWS – excessive appetite and temper outbursts, reported Shuang Liu of ConSyance. CSTI-500 is designed to ease hunger and trouble regulating emotional responses by blocking the reuptake of serotonin, dopamine and norepinephrine, the neurotransmitters involved in regulating mood, behaviour and sleep. No reports of severe side effects were observed and the therapy was deemed generally safe and well tolerated. CSTI-500, with its robust pharmacokinetic and safety data, has a strong foundation on which to proceed to a Phase 2 study.
Neuren Pharmaceuticals opened its first US-based site for the Phase 2 clinical trial of the investigational therapy and NNZ-2591. NNZ-2591 is a lab made version of a naturally occurring protein which regulates the signals involved in metabolism, growth and brain development that’s deficient in Prader-Willi Syndrome. In preclinical studies, NNZ-2591 normalized behavioral problems in a mouse model of PWS. During a previous Phase 1 clinical trial of 28 volunteers, NNZ-2591 was found to be safe and tolerated well and showed good blood absorption and brain access.
Harmony Biosciences plans to launch a Phase 3 clinical trial by the end of the year to investigate whether pitolisant can safely and effectively reduce excessive daytime sleepiness in children, adolescents and adults with Prader–Willi Syndrome. The Phase 2 trial indicated that pitolisant led to a meaningful drop of sleepiness on the Epworth Sleepiness Scale for Children and Adolescents (ESS_CHAD). After completing the 11th week treatment period, many participants entered a multi-year extension phase which will mean they will continue to receive pitolisant at the maximum ag- related dose until the end of the trial, expected by 2028.
Finally, Arcadia Pharmaceuticals has launched a Phase 3 clinical trial testing the safety and efficacy of ACP–101, an experimental carbetocin nasal spray for the treatment of hyperphagia in people with Prader-Willi Syndrome. ACP-101 contains carbetocin, a lab-form of oxytocin – a hormone involved in behaviours related to appetite and emotions, and was originally developed under the name LV-101 by Levo therapeutics then bought by Acadia in June 2022. Levo previously submitted a regulatory application to the US Food and Drug Administration seeking approval. The application was rejected in January 2022. The FDA’s response stated that further testing was required, despite the treatment appearing safe and well tolerated. The new trial will focus on a 3.2mg dose administered three times a day to help curb the insatiable appetite felt by people with PWS. The nasal spray has been granted special designations by the FDA which will hopefully speed its development and review.
