Soleno Reports Positive Top-line Results from Prader-Willi Study

Rare Daily Staff

Soleno Therapeutics reported positive top-line results from the randomized withdrawal period of Study C602, a long-term treatment study of DCCR Extended-Release tablets for the treatment of Prader-Willi syndrome.

The multi-center, randomized, double-blind, placebo-controlled randomized withdrawal period enrolled 77 patients previously enrolled in Study C602 who had been on open-label treatment with DCCR for between two and four years. Participants were randomized 1:1 to receive either DCCR or placebo for a period of four months.

The primary endpoint was the change from baseline in hyperphagia-related behaviors as assessed by the hyperphagia questionnaire for clinical trials (HQ-CT), a caregiver-completed nine item validated questionnaire for assessing hyperphagia in PWS. Secondary endpoints included investigator assessments of participants’ overall severity of illness and change in condition, as measured by Clinical Global Impression of Severity (CGI-S) and Clinical Global Impression of Improvement (CGI-I) ratings, respectively.

Hyperphagia-related behaviors markedly worsened in the placebo group compared to DCCR, represented by a highly statistically significant, clinically meaningful difference in mean change from baseline in the HQ-CT total score of 5.0 at week 16. Secondary endpoints of CGI-S and CGI-I both showed strong trends towards worsening in the placebo group compared to DCCR over the course of the randomized withdrawal period, respectively. DCCR continued to be generally well-tolerated in the randomized withdrawal period with no new or unexpected safety signals, including no serious adverse events or discontinuations due to adverse events occurring in any participants in the DCCR group.

Prader-Willi syndrome (PWS) occurs in an estimated one in every 15,000 live births. The hallmark symptom of this disorder is hyperphagia, a chronic and life-threatening feeling of intense, persistent hunger, food pre-occupation, extreme drive to food seek and consume food that severely diminish the quality of life for patients with PWS 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., obesity, diabetes, cardiovascular disease) and mortality (e.g., stomach rupture, choking, accidental death due to food seeking behavior). There are currently no approved therapies to treat the hyperphagia/appetite, metabolic, cognitive function, or behavioral aspects of the disorder.

DCCR is a novel, proprietary extended-release dosage form containing the crystalline salt of diazoxide and 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.

The DCCR development program is supported by data from five completed phase 1 clinical studies in healthy volunteers and three completed phase 2 clinical studies, one of which was in patients with PWS. In the PWS phase 3 clinical development program, DCCR showed promise in addressing hyperphagia, the hallmark symptom of PWS, as well as several other symptoms such as aggressive/destructive behaviors, fat mass and other metabolic parameters. Diazoxide choline has received Orphan Drug designation for the treatment of PWS in the United States and European Union, and Fast Track designation in the United States.

“These results will support our planned submission of a New Drug Application to the U.S. Food and Drug Administration mid-year of next year,” said Anish Bhatnagar, CEO of Soleno.

Photo: Anish Bhatnagar, CEO of Soleno