Results of DCCR Extension Study Support FDA Application, Soleno Says
One year of treatment with Soleno Therapeutics’ investigational oral therapy diazoxide choline controlled release, known as DCCR, significantly reduced excessive appetite and disease-related behaviors in Prader-Willi syndrome (PWS) patients, according to top-line data from an extension study of the DESTINY PWS Phase 3 trial.
These trajectories were significantly different from what happens in the natural course of the disease — which is being assessed in the ongoing observational PATH for PWS trial, or PfPWS (NCT03718416).
According to investigators, the findings further support DCCR’s therapeutic potential in the PWS patient population, for whom no specific treatment has been approved to date.
“We are extremely pleased with these results from our ongoing open-label extension study and their comparison to the PATH for PWS study,” Anish Bhatnagar, MD, Soleno’s CEO, said in a press release.
“We look forward to submitting the data from these studies to the U.S. Food and Drug Administration (“FDA”) in this quarter and remain firmly committed to the goal of obtaining approval for DCCR as a new treatment for people with PWS as expeditiously as possible,” Bhatnagar said.
In March, the FDA had told Soleno that an additional clinical trial would be needed to support any future application seeking DCCR’s approval for PWS. That requirement came after top-line results from the DESTINY PWS trial (NCT03440814) failed to show a significant reduction in hyperphagia or excessive hunger — the hallmark symptom of PWS and the study’s main goal.
However, an analysis showed that the COVID-19 pandemic greatly influenced the trial results, with pre-pandemic data demonstrating significant reductions in hyperphagia and behavioral symptoms with DCCR. The pre-COVID-19 data also showed significant improvements in communication and social interactions with the investigational therapy relative to a placebo, the analysis found.
Those results prompted PWS advocacy organizations to petition the FDA, asking it to reconsider its request for a new trial.
In July, the agency agreed to review additional data from DESTINY PWS and its extension study (NCT03714373, also called C602), as well as comparisons with natural history sources, such as the PfPWS study, to determine whether they prove sufficient to support a regulatory application.
Taken as a once-daily tablet, DCCR works by blocking the release of two appetite-stimulating proteins in the brain — neuropeptide Y and agouti-related protein — that are believed to drive hyperphagia.
In the DESTINY PWS study, also called C601, a total of 127 PWS patients, ages 4 and older, were randomly assigned to receive either DCCR or a placebo for 13 weeks (just over three months). Participants were recruited at 29 sites across the U.S. and the U.K.
Following the completion of the treatment period, 115 participants chose to enter the C602 extension study, in which all will receive the therapy for up to three years.
Now, Soleno shared top-line, one-year data from C602, in which 95 patients currently continue to receive DCCR.
The new results showed that one year of DCCR treatment significantly eased hyperphagia and behavior symptoms, while significantly improving body composition (with greater lean body mass) and the hormonal and metabolic profiles of PWS patients.
Notably, significant changes in hyperphagia and in all behavioral domains — aggressive behaviors, anxiety, compulsivity, depression, disordered thinking, and rigidity-irritability — were detected as early as 13 weeks (about three months).
DCCR’s safety profile was consistent with previous trials, with the most commonly reported adverse events including increases in blood sugar levels, excessive hair growth, and leg or hand swelling. No serious, unexpected, DCCR-related adverse events have been reported to date.
These data “further demonstrate that DCCR significantly reduced hyperphagia, as well as improved body composition, behaviors, and endocrine and metabolic measures over 52 weeks [one year],” said Evelien Gevers, MD, a pediatric endocrinologist at Barts Health NHS Trust and Queen Mary University of London, and the U.K. coordinating investigator of the DESTINY PWS and C602 studies.
The company also presented findings of a comparison between C602’s participants who received DCCR for six months and one year, and matched patients in the PfPWS study.
PfPWS, sponsored by the Foundation for Prader-Willi Research (FPWR), is following for up to four years 700 PWS patients living in the U.S., Canada, Australia, or New Zealand. It is expected to be completed by October 2022.
Patient matching and comparisons between studies were conducted by an external contract research organization, independent of Soleno, and considering the impact and timing of the COVID-19 pandemic.
Hyperphagia and behavioral symptoms, the evaluated outcomes in this analysis, were assessed with the same measures across studies.
The data showed that DCCR-treated patients had a significantly greater reduction in hyperphagia and all evaluated behavior symptoms after six and 12 months, compared with untreated, matched patients in the PfPWS study.
These findings “suggest that DCCR may provide a much needed and meaningful improvement to the lives of those living with PWS and their families,” said Theresa V. Strong, PhD, FPWR’s co-founder and director of research programs.
“We look forward to supporting the Soleno team as they advance DCCR through the regulatory process,” Strong added.
According to Gevers, this therapy could be a game-changer for patients who currently have no options.
“If approved, DCCR could offer people with PWS a meaningful option for long-term management of their symptoms,” she said.
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