FDA delays approval decision until March on DCCR for excessive hunger in PWS
Agency needs more time to review new data submitted by developer
The U.S. Food and Drug Administration (FDA) has delayed by three months its decision on whether to approve Soleno Therapeutics’ extended-release formulation of diazoxide choline — known as DCCR — for curbing excessive hunger in people with Prader-Willi syndrome (PWS). The therapy candidate is designed for use in PWS patients ages 4 and older.
That decision had been due at the end of this month, but the FDA now says it needs more time to review additional information recently submitted by Soleno. Those data, submitted at the agency’s request, were deemed a major amendment to the application. As a result, a decision by the regulatory agency is now expected by March 27, 2025.
The update came in a press release from Soleno, in which the company also noted that “the FDA did not cite any safety, efficacy or manufacturing concerns in [its] correspondence.”
In October, the agency had announced that an advisory committee meeting was not needed for the review of Soleno’s regulatory application for DCCR, which was filed in July.
The therapy has been granted breakthrough and fast track designations in the U.S., and orphan drug status in both the U.S. and the European Union, for PWS. Each of these designations provides companies with incentives designed to speed a therapy’s clinical development.
DCCR application supported by findings of DESTINY PWS study
Prader-Willi syndrome is caused by the loss of specific genes that control a wide range of bodily processes, including metabolism, growth, intellectual ability, social behavior, and appetite. Among the symptoms of PWS, which emerge between the ages of 1 and 4, are weak muscle tone, developmental delays, cognitive impairment, and behavioral problems.
Children with PWS develop hyperphagia, or an overwhelming and constant hunger. This can lead to obesity and associated conditions such as heart and lung disease, diabetes, high blood pressure, and gastrointestinal complications.
DCCR is a once-daily oral treatment designed to block the release of two appetite-stimulating proteins in the brain that are thought to drive hyperphagia. The medication also suppresses the release of insulin, a hormone that helps blood sugar (glucose) move from the blood into cells. This insulin blockade keeps more sugar in the blood, which boosts feelings of fullness.
To ensure constant therapy levels in the bloodstream with once-daily dosing, Soleno developed DCCR as an extended-release formulation, which begins dissolving in the stomach and continues in the bowel.
The company’s approval application is supported by data from several trials, including the Phase 3 DESTINY PWS study (NCT03440814) and its open-label extension study, dubbed C602 (NCT03714373).
DESTINY PWS, conducted at sites in the U.S. and the U.K., evaluated DCCR’s safety and efficacy against a placebo in 127 PWS patients, ages 4 and older. Although the therapy failed to outperform the placebo in reducing hyperphagia, further analyses suggested the COVID-19 pandemic may have influenced the results.
About 90% of DESTINY PWS participants chose to enroll in its open-label extension study C602, in which all were to receive the therapy for up to three years. One-year data showed that DCCR treatment significantly lessened hyperphagia and behavioral problems while increasing lean body mass.
These trajectories were found to be significantly different from those seen among untreated, matched patients participating in the ongoing observational PATH for PWS trial (NCT03718416).
However, the FDA still asked for more clinical trial data, so Soleno started a withdrawal period in the extension study. Data showed that, during this period, patients who switched to a placebo experienced worsening hyperphagia and weight gain compared with those who continued on DCCR.
Up to five years of DCCR treatment is also available for eligible C602 study participants in a second open-label extension study called C614 (NCT05701774). That trial is slated to run through 2028.
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