Soleno Therapeutics announces top-line results from phase III trial of DCCR for treatment of Prader-Willi syndrome.

Soleno Therapeutics, Inc. announced top-line results from the Company’s Phase III trial, DESTINY PWS (C601), evaluating once-daily Diazoxide Choline Controlled Release (DCCR) tablets for patients with Prader-Willi Syndrome (PWS)

: DESTINY PWS/C601 :The study did not meet its primary endpoint of change from baseline in hyperphagia. The change was measured by the total score of a Hyperphagia Questionnaire for Clinical Trials (HQ-CT, 0?36). An improvement in HQ-CT is represented by a decrease in the score. The mean (SE) change from baseline for DCCR was -5.94 (0.879) and for placebo was -4.27 (1.145). The least squares mean difference in HQ-CT score of DCCR compared with placebo was -1.67 (1.294); 95% confidence interval (-4.24, 0.89); p=0.1983. Significant changes were observed in two of three key secondary endpoints from baseline to week 13 in subjects receiving DCCR as compared to placebo: 1. Improvement in Clinical Global Impression of Improvement (CGI-I) score as assessed by the investigator (p=0.029). 2. Reduction of body fat mass measured by DXA scan (p=0.025).

In a prespecified subgroup of subjects (n=61) with more severe hyperphagia, as identified by a dichotomized median baseline HQ-CT score of >22, the mean (SE) change from baseline for DCCR (n=42) was -9.67 (1.429) and for placebo (n=19) was -4.26 (1.896). The least squares mean difference in HQ-CT score of DCCR compared with placebo was -5.41 (2.093); 95% confidence interval (-9.60, -1.22); p=0.0124. In addition to the reduction in total body fat mass, other body composition changes in DCCR compared to placebo included significant decreases in trunk fat mass (p = 0.047), and improvement in lean body mass to fat mass ratio (p=0.001). Fat mass changes were most pronounced in subjects in the highest weight band (n=18, 100-135 kg); p=0.024.

DESTINY PWS is a multi-center, randomized, double-blind, placebo-controlled study of once-daily oral administration DCCR in 127 PWS patients at 29 sites in the U.S. and UK. The objective of the study was to assess the safety and efficacy of DCCR in subjects ages four years and older, with genetically-confirmed PWS. Patients who completed the double-blind study were eligible to enroll in study C602.

Study C602 – Long-term Safety Extension Study – Interim Data ; A total of 115 subjects were enrolled into C602, an ongoing open-label, safety extension study of DCCR in PWS patients completing C601, and greater than 90% of them are continuing to be treated at this time. An interim analysis of subjects (n=63) who have completed three months of treatment on C602 shows continuing improvements in hyperphagia. DCCR subjects from C601 (n= 38) at six months of treatment demonstrated a reduction in hyperphagia score of -11.7 (-48%) and placebo subjects from C601 who switched to DCCR showed a similar change following three months of treatment in C602. Behaviors related to PWS are measured using a PWS Profile Questionnaire (PWS-P), which consists of caregiver responses to questions in six domains: aggressive behaviors, anxiety, rigidity-irritability, compulsivity, depression and disordered thinking. Improvements in most domains were seen in C601 with DCCR treatment. In subjects from C601 treated with DCCR, each domain showed further improvement in C602. Placebo subjects from C601 who switched to DCCR showed a similar change following three months of treatment in C602.

PWS Outcomes Study – Interim Data : An interim analysis of a subset of subjects in the PWS outcomes study was conducted consisting of data from interviews at the end of C601 for caregivers of 27 patients (17 DCCR and 10 placebo). The interviews evaluated individual patient experiences with DCCR and placebo using three domains: food-related improvements, non-food-related improvements and daily life improvements. In each of these domains, approximately 48% participants on DCCR reported at least some positive improvement, with 18-24% reporting a major improvement in the PWS patient. In the placebo group, a single participant (10%) reported a minor improvement in their PWS patient, and none reported a major difference.

“While we are disappointed to have not achieved statistical significance on the study’s primary endpoint, we are excited by the results observed in those subjects with severe hyperphagia, as well as the changes in body composition and behavioral endpoints,” said Anish Bhatnagar, M.D., Chief Executive Officer of Soleno Therapeutics. “Based on these data, we will continue treatment of patients on C602. We are continuing to evaluate the data from C601 and C602 and plan to meet with regulatory authorities to determine next steps. On behalf of the Soleno team, I would like to thank the patients, families and investigators involved in this study, as well as the Foundation for Prader-Willi Research and Prader-Willi Syndrome Association USA and UK, for their support of the DCCR Phase III development program.”

DCCR Safety :The safety profile of DCCR in C601 was generally consistent with the known profile of diazoxide and prior experience with DCCR. Treatment emergent adverse events (TEAEs) were reported in 70 (83.3%) DCCR subjects and 31 (73.8%) placebo subjects. TEAEs that were reported more frequently in the DCCR group vs. placebo and occurred in at least 5% of DCCR subjects were hypertrichosis (35.7% vs. 14.3%), peripheral edema (20.2% vs 9.5%), blood glucose increase (6% vs. 4.8%), hyperglycemia (11.9% vs. 0%) and pyrexia (6% vs. 0%). Most events were Grade 1 in severity, including all events of hypertrichosis (other than one Grade 2 in the placebo group). No Grade 4 or higher events were reported in this study. Five subjects discontinued from the study early due to adverse events, four in the DCCR group and one in the placebo group. Six subjects had serious TEAEs in the DCCR group and none in the placebo group. There were no serious unexpected adverse events (SUSARs) related to DCCR.

Study visits in C601 and C602 conducted after approximately mid-March were impacted by COVID-19. Certain evaluations could have been conducted in a different manner and evaluations, such as DXA, were not conducted in most cases during this period. Additional analyses will evaluate the impact of these changes.