Soleno Therapeutics, Inc. announced publication of one-year results from the Phase 3 DESTINY PWS study and the open-label extension period of Study C602 evaluating investigational, once-daily DCCR (Diazoxide Choline) Extended-Release tablets for patients with Prader-Willi syndrome (PWS). The paper, entitled "Diazoxide Choline Extended-Release Tablet in People with Prader-Willi Syndrome: Results from Long-Term Open-Label Study," was published in the peer-reviewed journal Obesity. The publication features results from 52-week administration of DCCR in participants with PWS enrolled in DESTINY PWS and/or Study C602, the long-term open-label extension study of participants who completed DESTINY PWS.

The primary efficacy endpoint was change in hyperphagia total score from baseline, as measured using the Hyperphagia Questionnaire for Clinical Trials (HQ-CT). Other endpoints included behavioral assessments using the PWS Profile Questionnaire (PWSP), body composition, hormonal and metabolic measures, disease severity and safety. Key Highlights from the Publication: Primary Endpoint: Hyperphagia: Statistically significant, clinically meaningful decreases in HQ-CT total score (mean [SE]) from baseline in overall population after receiving DCCR for 52 weeks (-9.9 [0.77]; p<0.0001).

Highly significant, clinically meaningful decreases in HQ-CT total score from baseline were also observed after receiving DCCR for 13, 26, and 39 weeks (all p<0.0001). In participants with severe hyperphagia at baseline, 52-week DCCR treatment resulted in significantly greater reduction in HQ-CT score compared to the overall population (-15.2 [1.39]; p<0.0001). Other Endpoints: PWS related behaviors: Statistically significant improvements in all behavioral domains of the PWSP, which consist of aggressive behaviors, anxiety, compulsivity, depression, disordered thinking, and rigidity/irritability (all p<0.0001).

Body composition: Significant improvements in lean body mass:fat mass ratio were seen (p=0.0005), consistent with increases in lean body mass (p<0.0001) and no significant changes in body fat mass. Hormonal and metabolic measures: Significant reductions in serum leptin (p<0.0001) and insulin (p=0.0004) and improvement in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (p=0.0033), consistent with the proposed mechanism of action of DCCR in PWS. In addition, a significant increase in adiponectin was observed (p<0.0001).

Disease severity: Significant reduction in disease severity as assessed by both clinicians and caregivers using Clinical Global Impression of Severity and Caregiver Global Impression of Severity scores, respectively (both p<0.0001). Safety: DCCR was well-tolerated overall. Safety results are consistent with the safety profile of DCCR, with the most common drug-related treatment-emergent adverse events of hypertrichosis, peripheral edema, and hyperglycemia, the majority of which were grade 1 and infrequently resulting in study drug discontinuation.

DCCR has orphan designation for the treatment of PWS in the U.S. and EU and Fast Track designation from the U.S. FDA. Soleno recently announced positive topline results from its randomized withdrawal phase of Study C602. The U.S. Food and Drug Administration (FDA) previously acknowledged that data from this study has the potential to support an NDA submission for DCCR.

Soleno anticipates submission of an NDA to the FDA in mid-2024.