The Data Safety Monitoring Board recommended the continuation of Soleno Therapeutics’ Phase 3 clinical trial evaluating the effects of diazoxide choline controlled release (DCCR) treatment in children and adults with Prader-Willi syndrome (PWS), the company announced.
Hyperphagia (excessive eating) is a classic PWS symptom caused by hormonal or cell-signaling disturbances, leading to obesity. Specifically, two neuropeptides — neuropeptide Y (NPY) and agouti-related protein (AgRP) — that some nerve cells release are believed to trigger the excessive appetite experienced by these patients.
DCCR can inhibit the release of NPY and AgRP by opening (activating) potassium channels. As a result, the activated potassium channels promote fat metabolism, and decrease the appetite by lowering appetite-stimulating signaling.
The randomized, placebo-controlled Phase 3 study, DESTINY PWS (NCT03440814), was designed to evaluate the effects of once-daily administration of DCCR (75–450 mg) on about 100 patients diagnosed with PWS. The trial includes both children (age 4 and up) and adults, and compares questionnaire-based hyperphagia scores — measuring hyperphagia-related behavior — between baseline and 13 weeks of treatment.
Secondary endpoints include comparisons of patients’ body fat mass, and the clinical progress estimated by clinicians and caregivers.
The Data Safety Monitoring Board (DSMB) — an independent group of clinical experts including physicians, statisticians, and patient advocates — based the recommendations on safety information reviews. The board can recommend continuation of studies without modifications, with modifications, or termination of studies, based on these reviews.
“We are delighted with the DSMB’s positive recommendation to continue the Phase 3 trial as planned as it further supports DCCR’s safety profile,” Anish Bhatnagar, PhD, chief executive officer of Soleno, said in a press release. “We are continuing to enroll patients with 14 sites activated in DESTINY PWS.”
Also, patients who complete the DESTINY trial can choose to take part in the continuing C602, which is a 9-month, open-label safety extension study.
An earlier Phase 2 trial on 13 PWS patients showed an appetite-reducing and fat-lowering effect upon treatment with increasing doses of DCCR (1.5 mg/kg up to 4.2 mg/kg). According to the results, patients receiving the higher dose lost more fat.
Diazoxide choline was granted orphan drug designation for the treatment of PWS in the U.S. and EU. In addition, in 2018, the U.S. Food and Drug Administration issued DCCR a Fast Track designation to help development of the therapy.