New DCCR Trial May Include Current DESTINY Trial Patients, FDA Says
The U.S. Food and Drug Administration (FDA) continues to call for an additional clinical trial of Soleno Therapeutics’ diazoxide choline controlled release (DCCR) tablets before considering it for approval for Prader-Willi syndrome (PWS).
However, the agency agreed that such a trial, if appropriately designed, may involve patients currently receiving the therapy on the extension study (NCT03714373, also called C602) of the DESTINY PWS Phase 3 trial — an approach that “would significantly reduce the time and cost to obtain the necessary data,” Anish Bhatnagar, MD, Soleno’s CEO, said in a press release.
These were the conclusions of a December meeting between Soleno and the FDA’s Division of Psychiatry. Its goal was to discuss whether the data submitted to the agency in October was sufficient to support a request for DCCR’s approval, as well as possible ways to generate additional appropriately-controlled clinical results.
“We appreciate the constructive dialogue with the FDA and the potential to obtain additional controlled clinical data from participants already enrolled in C602,” Bhatnagar said.
Soleno expects to submit a study proposal to the agency in the near future and, if acceptable, plans to start the trial soon after. In the meantime, the company will continue to prepare DDCR’s regulatory submission, while the additional data are collected, Bhatnagar noted.
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, or insatiable hunger, the hallmark symptom of PWS.
In a previous open-label Phase 1/2 trial (NCT02034071), DCCR was shown to result in early and sustained drops in hyperphagia, body fat loss, and fewer aggressive and violent behaviors in PWS patients, compared with a placebo.
However, top-line data from DESTINY PWS (NCT03440814), which involved 127 PWS patients, 4 and older, showed that the therapy was not superior to a placebo at easing hyperphagia — failing the study’s main goal.
An analysis of pre-COVID-19 pandemic trial data revealed significant reductions in hyperphagia and behavioral symptoms, as well as improvements in communication and social interactions, with DDCR relative to a placebo.
This suggested that the pandemic greatly influenced the trial’s top-line results, which prompted PWS advocacy organizations to ask the FDA to reconsider its prior request for a new trial to support any future application seeking DCCR’s approval for PWS.
In July, the agency agreed to review additional data from DESTINY PWS and its extension study, as well as comparisons with natural history sources, to determine whether they proved sufficient to support a regulatory application.
C602, which enrolled 115 patients who completed DESTINY PWS, was designed to assess DDCR’s one-year safety and effectiveness. All participants are receiving the experimental therapy for up to three years.
Top-line, one-year data, showed that the therapy significantly lessened hyperphagia and behavioral symptoms, while significantly improving body composition (with greater lean body mass) and the hormonal and metabolic profiles of PWS patients. Such benefits were detected as early as 13 weeks (about three months).
In addition, DCCR-treated patients had a significantly greater reduction in hyperphagia and all evaluated behavioral symptoms after six and 12 months, compared with untreated, matched patients in the PATH for PWS, or PfPWS, natural history study (NCT03718416).
PfPWS, sponsored by the Foundation for Prader-Willi Research, is following 700 PWS patients for up to four years in the U.S., Canada, Australia, and New Zealand.
To date, DDCR has been generally safe and well-tolerated, with the most frequently reported adverse events being increases in blood sugar levels, excessive hair growth, and leg or hand swelling.