Soleno Meets with FDA After Phase 2 Trial Evaluating DCCR in Prader-Willi Syndrome

Soleno Therapeutics and the U.S. Food and Drug Administration recently held a meeting to mark the end of a successful Phase 2 clinical trial evaluating diazoxide choline controlled-release (DCCR) for the treatment of Prader-Willi syndrome (PWS).

DCCR is an extended-release, crystalline salt formulation of diazoxide designed to be administered once-daily in the form of a tablet. Diazoxide has been used for decades in a few rare diseases in newborns, infants, children, and adults, but never in PWS.

In the PWS Phase 2 study (PC025), DCCR reportedly showed promise in addressing the hallmark symptoms of PWS, especially hyperphagia (abnormally increased appetite). The trial was a randomized withdrawal study that enrolled 13 obese subjects with confirmed PWS between the ages of 11 and 21.

A first phase of the study was open-label, during which participants were given a DCCR dose that escalated every 14 days. The 10-week treatment phase was followed by a randomized, placebo-controlled, withdrawal phase.

Responders — or those who showed an increase in resting energy expenditure and/or a reduction in hyperphagia from baseline at certain study visits — were randomized in a 1:1 ratio either to continue on active treatment at the same dose they were already receiving or to the placebo equivalent of that dose for four extra weeks.

Of the 13 subjects who enrolled, 11 were designated as responders; the remaining two subjects discontinued prematurely.

Key efficacy results included a statistically significant reduction in hyperphagia from baseline to the end of the open-label treatment phase. In addition, greater improvement in hyperphagia was observed in patients who received DCCR doses of 4.2 mg/kg.

During the open-label phase, researchers also observed a mean decrease in body fat mass and an increase in lean body mass, a statistically significant reduction in waist circumference, and significant reductions in LDL cholesterol and non-HDL cholesterol. The change in triglycerides, while marked, did not reach statistical significance.

Based on the promising results of this Phase 2 study, the company is planning to continue advancing DCCR as a once-daily oral tablet for the treatment of Prader-Willi syndrome into a Phase 3 clinical trial in 2018.

“Alignment with the FDA on our Phase 3 clinical trial design of DCCR in PWS allows us to confidently initiate this study,” Anish Bhatnagar, MD, the CEO of Soleno, said in a press release. “If approved, we believe DCCR has the potential to be a safe and effective treatment for PWS, a rare and life-threatening disease with significant unmet needs.”

In May 2014, diazoxide choline received orphan drug status in the United States for the treatment of PWS. In October 2017, the European Medicines Agency granted the drug the same designation.

Soleno develops new therapies for the treatment of rare diseases like PWS, a complex genetic neurobehavioral/metabolic disorder. There are currently no approved therapies to treat the symptoms of PWS.