FDA Tells Soleno It Will Need to Conduct Additional Study for Prader-Willi Therapy

Rare Daily Staff

The U.S. Food and Drug Administration told Soleno Therapeutics that existing data on extended release DCCR tablets for the treatment of Prader-Willi Syndrome is inadequate to support an approval and that it would need to conduct an additional phase 3 clinical trial.

Prader-Willi syndrome is characterized by 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., 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. DCCR (Diazoxide Choline) has received Orphan Drug designation for the treatment of PWS in the U.S. and EU, and Fast Track designation in the United States.

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 PWS patients. In the PWS phase 3 study, 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.

Following a meeting with the FDA in November about existing data from studies with DCCR to support a New Drug Application for the treatment of Prader-Willi syndrome, Soleno submitted additional analyses to the agency from the company’s phase 3 trial, DESTINY PWS.

These data were from study visits that were completed prior to the significant disruptions caused by the COVID-19 pandemic. The data analyses showed statistically significant changes for DCCR compared to placebo in the primary and key secondary endpoints.

Nevertheless, after revieing the data the FDA informed Soleno that an additional controlled clinical trial will be necessary to support an NDA submission for DCCR in Prader-Willi.

“We intend to continue the dialogue with the FDA to ensure that DCCR is approved for individuals with PWS as expeditiously as possible,” said Anish Bhatnagar, CEO of Soleno Therapeutics. “Based on the totality of data generated to date, we remain confident in DCCR’s potential to address the unmet need for a safe and effective treatment option for PWS patients. We are currently evaluating the appropriate next steps for our DCCR program.”

Photo: Anish Bhatnagar, CEO of Soleno Therapeutics