DCCR Trials’ New Data Show Sustained Easing of Hunger, Disruptive Behaviors

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by Lindsey Shapiro, PhD |

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A year of treatment with DCCR (diazoxide choline controlled release) tablets, Soleno Therapeutics’ investigational therapy for people with Prader-Willi syndrome (PWS), safely led to sustained reductions in excessive hunger and disease-related behaviors, according to two presentations of data from a Phase 3 trial and its open-label extension.

Soleno announced positive findings from the trials last year, and the company has since been in ongoing talks with the U.S. Food and Drug Administration (FDA) regarding a need for further clinical testing of the potential treatment.

“We believe that these encouraging results show a long term, beneficial effect of DCCR on hyperphagia and other behaviors in patients with PWS when compared with the natural history of the disease,” Theresa Strong, PhD, director of research programs at the Foundation for Prader-Willi Research (FPWR), said in a press release.

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“These results demonstrate that DCCR may be an effective treatment option for individuals with PWS, where behavioral abnormalities are very difficult to treat. FPWR continues to be encouraged by DCCR’s potential to provide meaningful improvement to patients living with PWS and we look forward to continuing to support Soleno through the regulatory process,” Strong added.

DCCR is a once-daily oral therapy that acts by blocking the release of two appetite-stimulating proteins in the brain — neuropeptide Y and agouti-related protein — which are thought to drive hyperphagia or excessive hunger, a hallmark symptom of PWS.

The Phase 3 DESTINY PWS trial (NCT03440814) evaluated the effects of DCCR on hyperphagia against a placebo over a period of 13 weeks. Data showed that DCCR overall failed to meet its primary goal of lowering hyperphagia, prompting the FDA to request further clinical testing prior to considering DCCR for regulatory approval.

However, additional analyses suggested that the COVID-19 pandemic may have significantly disrupted the trial, and the FDA agreed to review additional data from DESTINY and its open-label extension, called C602 (NCT03714373), to determine if they would be sufficient to support DCCR’s regulatory approval.

Strong presented some of these data in the poster “Comparison of hyperphagia and behavioral features in Prader-Willi Syndrome (PWS) patients receiving Diazoxide Choline Extended-Release (DCCR) with matched participants in PATH for PWS Study (PfPWS NHS),” at the Pediatric Academic Societies 2022 Virtual Annual Meeting.

Collective data from DESTINY/C602 included 114 children with a mean age of 13.1, all of whom received DCCR. They were compared with a matched group of 229 untreated patients enrolled in the PATH for PWS natural history study (NCT03718416) sponsored by the FPWR.

DCCR’s use led to significant reductions in hyperphagia at 26 weeks (about six months) compared with the natural history group, as measured with the Hyperphagia Questionnaire for Clinical Trials (HQ-CT), results showed. These changes were sustained up to 52 weeks (one year).

Caregiver questionnaires supported DCCR also leading to greater improvements in aggression, anxiety, irritability, compulsivity, depression, and disordered thinking than were observed in the untreated children, with these behavioral changes also sustained for one year.

Notably, improvements were seen regardless of a child’s age, level of hyperphagia at study start, use of growth therapy or PWS cause at the study’s start.

A second presentation, “An open-label, long-term safety and efficacy evaluation of diazoxide choline extended-release (DCCR) tablet in participants with Prader-Willi Syndrome,” was given by Jennifer Miller, MD, a University of Florida professor of pediatric endocrinology, at the Pediatric Endocrinology Society 2022 Virtual Annual Meeting.

Miller reported additional benefits of DCCR treatment over one year that included an increase in the ratio of lean body mass to fat mass, and improvements in some metabolic and hormonal markers including leptin — a protein the body produces to curb appetite — as well as adiponectin and insulin, which are both involved in blood sugar regulation.

Insulin resistance, or the body’s poor response to insulin that prevents it from using sugar in the blood for energy, was also eased after one year of treatment.

As has been previously observed, DCCR was generally well-tolerated and safe.

“These important data add to the growing body of evidence showing the long-term benefits of DCCR in patients with PWS, affirming our confidence in DCCR as a potential treatment for patients with PWS,” said Anish Bhatnagar, MD, CEO of Soleno.

These collective findings have been given to the FDA “as part of ongoing discussions regarding the clinical data needed to support a potential New Drug Application (NDA) for DCCR in PWS, and we look forward to continued discussions with the FDA,” Bhatnagar added.

Soleno announced in January that the regulatory agency, while still expecting DCCR to go through further clinical testing, had agreed that a new clinical trial could include DESTINY/C602 participants to save time and cost.