DCCR Leads to Continuous Reductions in Hyperphagia, Other Symptoms
Daily treatment with diazoxide choline controlled release (DCCR) leads to sustained reductions in excessive appetite and other symptoms of Prader-Willi syndrome (PWS), according to updated findings from a Phase 3 trial.
“The results from this program continue to demonstrate DCCR’s beneficial impact on hyperphagia [excessive appetite], the predominant symptom of PWS, other behaviors typical of PWS, as well as problems related to body composition, and a safety profile that is well understood,” Jennifer L. Miller, MD, a pediatric endocrinologist at the University of Florida and a principal investigator of the study, said in a press release. She presented these top-line results at the Foundation for Prader-Willi Research‘s recent annual Research Symposium.
“We expect to meet with the U.S. Food and Drug Administration [FDA] before year-end to determine next steps and a potential path forward to address the unmet need for a safe and effective treatment option for PWS patients,” said Anish Bhatnagar, MD, CEO of Soleno Therapeutics, which is developing DCCR.
DCCR is an extended-release formulation of diazoxide. It blocks the release of neuropeptide Y and agouti-related protein, two proteins found in the brain that are believed to stimulate hyperphagia.
The DESTINY PWS Phase 3 trial (NCT03440814), also called C601, investigated the efficacy and safety of once-daily DCCR among 127 participants, ages 4 and older, with genetically confirmed PWS. Participants who completed this study could then enroll in C602 (NCT03714373), an ongoing extension study monitoring treatment for up to three years.
Although the trial did not meet its primary goal of reducing hyperphagia, or insatiable appetite, Soleno did observe a significant relationship between higher DCCR concentration in patients’ blood and greater reductions (benefits) from baseline — the start of the study — in scores on the Hyperphagia Questionnaire for Clinical Trials (HQ-CT).
“An interim analysis of the subset of patients who completed 13 weeks of treatment on C602 showed a continued improvement in hyperphagia, as well as several other PWS related behaviors,” the company stated.
Soleno also reported significant changes in two secondary goals comparing DCCR with a placebo: the physician-assessed Clinical Global Impression of Improvement score and reduction of body fat mass.
Analyses revealed that DCCR treatment was associated with continued efficacy and other positive outcomes, as compared to the worsening seen among patients taking a placebo.
Although HQ-CT scores initially declined more in participants on placebo, they began to worsen from week four, while those taking DCCR continued to improve.
DCCR treatment lowered patients’ leptin levels and boosted adiponectin, reversing trends seen in obesity and cardiovascular disease.
Likewise, DCCR reduced fasting insulin levels and significantly eased insulin resistance, in which the body’s cells have difficulties absorbing glucose sugar from the blood. This can lead to increased hunger, high blood pressure, and weight gain.
HQ-CT score changes showed sustained improvements for patients treated with DCCR. A median score of 23 at the start of the C601 study fell to a median score of nine at week 13 of C602. Nearly all 63 participants on DCCR experienced improvements in the HQ-CT score, Soleno said.
Treatment was further linked to improvements in other PWS-related behaviors, such as anxiety, rigidity, compulsivity, and aggression.
No serious adverse events related to DCCR have been reported to date.
According to Soleno, more than 100 patients continue receiving DCCR in C602 and more than 20 have been treated for over a year.
“The sum total of data presented to date suggest that DCCR, if approved, may be a safe and effective treatment option that can address both the behavioral and metabolic components of PWS,” Miller said. “I look forward to continued progress in advancing DCCR as the first potentially approved treatment for key unmet needs associated with PWS.”
DCCR received fast track status from the FDA and orphan drug designations in the U.S. and the European Union for the treatment of PWS.