Breakthrough Clinical Results
Soleno Therapeutics announced multiple presentations at the 2025 United in Hope: International Prader-Willi Syndrome Conference. The presentations will cover long-term efficacy, swallowability, dosing compliance, impact on hyperphagia, safety in patients with pre-diabetes or diabetes, and comparisons to a natural history study of Diazoxide Choline Extended-Release (DCCR) tablets in treating hyperphagia in Prader-Willi Syndrome (PWS). The conference, a joint effort of several PWS organizations, is expected to be the largest ever focused on PWS. Soleno highlights its commitment to advancing research and working with advocacy groups to improve the lives of those affected by PWS.
Key Highlights
- Multiple presentations on Diazoxide Choline Extended-Release (DCCR) tablets at the 2025 International Prader-Willi Syndrome Conference.
- Data presented includes long-term efficacy, swallowability, dosing compliance, and impact on hyperphagia.
- Conference represents a unique collaboration between leading PWS organizations.
- Soleno emphasizes its commitment to research and collaboration with advocacy groups.
Incidence and Prevalence
Global Epidemiology of Prader-Willi Syndrome
Prevalence and Incidence
Prader-Willi syndrome is the most common genetic cause of life-threatening obesity in humans. It is characterized as a complex neuroendocrine disorder that affects populations worldwide.
The incidence of Prader-Willi syndrome is reported to be 1 in 10,000 to 25,000 individuals. Another source indicates a prevalence of 1 in 10,000 to 15,000 live births. A different study described Prader-Willi syndrome as affecting approximately 1/15,000-1/30,000 people.
According to a consensus guideline, PWS affects between 1:10,000 and 1:30,000 individuals.
Regional Variations
The prevalence of Prader-Willi syndrome varies across different regions:
- In Australia, birth prevalence of DNA proven Prader-Willi syndrome was estimated at 4 per 100,000 live births or approximately 1/25,000 live births per annum based on a study of 30 infants reported to the Australian Paediatric Surveillance Unit between 1998 and 2000
- In the Australian state of Victoria, the birth prevalence for individuals with a molecular diagnosis of PWS was estimated to be 1:15,830 for the period 2003-2012
- In the Swedish population, prevalence is reported as 1 in 8,000
- In the United Kingdom, prevalence is reported as 1 in 54,000
Recent Findings
A diagnostic study screening 16,579 infants found prevalence estimates of 1 in 8,290 for PWS, which is higher than previously reported rates. The same study confirmed 2 PWS cases among the 16,579 screened infants.
Global Estimates
It is estimated that there are 350,000-400,000 people with this syndrome worldwide.
In the United States, the Prader-Willi Syndrome Association USA knows of more than 3,400 persons with Prader-Willi syndrome out of an approximate 17,000-22,000 estimated to have the condition in the country.
In the general population, PWS occurs in 1 in 10,000-16,000 live-born infants, with approximately 60 people in every 1,000,000 being affected.
Historical Context
Prader-Willi syndrome was first medically described by Prader, Labhart and Willi in 1956. It was one of the first examples in humans of genetic imprinting, along with Angelman syndrome.
Challenges in Research
The low prevalence of this syndrome makes group-based physical activity interventions difficult in children, which may impact research efforts and therapeutic approaches.
Risk Factors and Comorbidities
Risk Factors and Comorbidities of Prader-Willi Syndrome
Risk Factors for Prader-Willi Syndrome
It's important to note that Prader-Willi syndrome (PWS) is a genetic disorder with specific causes rather than risk factors for occurrence. The genetic basis includes:
- Deletion of paternal genes in the PWS critical region on 15q11-q13 (approximately 70% of cases)
- Maternal uniparental disomy (UPD) of chromosome 15 (approximately 28% of cases)
- Mutation, deletion, or defect in the imprinting center (<2% of cases)
Major Comorbidities of Prader-Willi Syndrome
PWS is associated with numerous comorbidities that significantly impact patients' health and quality of life:
Primary Comorbidities:
- Childhood-onset obesity - PWS is described as "the most common genetic cause of obesity"
- Intellectual disabilities and behavioral problems
- Hyperphagia (excessive eating)
Additional Significant Comorbidities:
- Neonatal hypotonia and poor suck (present in >97% of patients)
- Developmental delay (present in 98% of patients)
- Hypogonadism and abnormal sexual maturation
- Short stature with small hands and feet
- Characteristic facial features (including almond-shaped eyes, narrow bifrontal diameter, thin upper lip)
- Speech and language impairments
- Hypothalamic dysfunction leading to various hormone deficiencies, including growth hormone deficiency
Health Complications:
PWS patients also face numerous health complications, including:
- Cardiovascular disease risk (elevated C-reactive protein levels >3.0 mg/L)
- Diabetes mellitus
- Sleep disturbances
- Dental problems (marked dental caries and enamel hypoplasia)
- Abnormal body composition with increased body fat and deficit of lean body mass
- Orofacial dysfunction, poor oral hygiene, severe tooth wear, and thick sticky saliva
- Psychotic illness (particularly in those with maternal uniparental disomy subtype, where rates exceed 60% by early adult life)
The management of PWS requires a multidisciplinary approach to address these various comorbidities and improve patient outcomes.
Drug used in other indications
Diazoxide Choline Extended-Release (DCCR) Clinical Indications
Based on the available information, there is no data regarding clinical indications beyond Prader-Willi syndrome that are currently under investigation for Diazoxide Choline Extended-Release (DCCR) tablets. The reviewed information exclusively focuses on DCCR's application in treating Prader-Willi syndrome, with no mention of other conditions or therapeutic uses.
Similarly, there is no information available about intervention models, study designs, or treatment protocols for DCCR trials in indications other than Prader-Willi syndrome, as all the provided information relates solely to DCCR's use in Prader-Willi syndrome.
Regarding the mechanism of action of DCCR that might support its investigation for multiple therapeutic indications, the available information does not provide any details on this aspect.