Soleno Therapeutics reported top-line results from the phase 3 study DESTINY PWS (C601), evaluating once-daily Diazoxide Choline Controlled Release (DCCR) tablets for patients with Prader-Willi Syndrome (PWS). The study did not meet statistical significance for the primary endpoint but did show significant improvements in a prespecified subgroup of patients with severe hyperphagia.
DESTINY PWS (C601) is a multi-center, randomized, double-blind, placebo-controlled study of once-daily oral administration DCCR in 127 PWS patients at 29 sites in the U.S. and UK. The objective of the study was to assess the safety and efficacy of DCCR in subjects ages four years and older, with genetically-confirmed PWS. Patients who completed the double-blind study were eligible to enroll in study C602, an ongoing open-label, safety extension study.
The study did not meet its primary endpoint of change from baseline in hyperphagia. Significant changes were observed in two of three key secondary endpoints from baseline to week 13 in subjects receiving DCCR as compared to placebo: Improvement in Clinical Global Impression of Improvement (CGI-I) score as assessed by the investigator and reduction of body fat mass measured by DXA scan. In a prespecified subgroup of subjects (n=61) with more severe hyperphagia, the mean change from baseline for DCCR was significant. In addition to the reduction in total body fat mass, other body composition changes in DCCR compared to placebo included significant decreases in trunk fat mass and improvement in lean body mass to fat mass ratio. Fat mass changes were most pronounced in subjects in the highest weight band (n=18, 100-135 kg).
Interim analysis of the ongoing extension study (C602) showed further reductions in hyperphagia of 48% after six months of DCCR treatment.
Soleno Therapeutics will continue to treat patients in study C602. Once the data from C601 and C602 are fully evaluated. The company plans to meet with regulatory authorities to determine next steps.
Diazoxide choline has received Orphan Drug Designation for the treatment of PWS in the U.S. and EU, and Fast Track Designation in the U.S.
Prader-Willi syndrome is caused by genetic changes on an “unstable” region of chromosome 15 that affects the regulation of gene expression. The hallmark symptom of this disorder is hyperphagia, a chronic feeling of insatiable hunger that severely diminishes the quality of life for PWS patients and their families. Additional characteristics of PWS include behavioral problems, cognitive disabilities, low muscle tone, short stature (when not treated with growth hormone), the accumulation of excess body fat, developmental delays, and incomplete sexual development. Hyperphagia can lead to significant morbidities (e.g., stomach rupture, obesity, diabetes, cardiovascular disease) and mortality (e.g., choking, accidental death due to food seeking behavior). The Prader-Willi Syndrome Association USA estimates that one in 12,000 to 15,000 people in the U.S. have PWS.
About Diazoxide Choline Controlled-Release (DCCR) Tablet
Diazoxide Choline Controlled-Release tablet is a novel, proprietary extended-release, crystalline salt formulation of diazoxide, which is administered once-daily. The parent molecule, diazoxide, has been used for decades in thousands of patients in a few rare diseases in neonates, infants, children and adults, but has not been approved for use in PWS. Soleno conceived of and established extensive patent protection on the therapeutic use of diazoxide and DCCR in patients with PWS.