FDA Will Require Additional Trial of DCCR for Approval, Soleno Says

The U.S. Food and Drug Administration (FDA) has told Soleno Therapeutics that an additional clinical trial “will be necessary” to support any future application seeking approval of diazoxide choline controlled release (DCCR) tablets for people with Prader-Willi syndrome (PWS), the company said.

Soleno had submitted an updated analysis from its DESTINY PWS Phase 3 clinical trial to the FDA in hopes that the data to date on its DCCR tablets would prove sufficient to support such an application.

That analysis, which showed that DCCR helped curb excessive hunger and ease behavioral symptoms in PWS patients, was conducted after the disappointing top-line results that followed the study’s completion in spring 2020 — at the height of the COVID-19 pandemic and its resulting lockdowns. Soleno had used pre-pandemic data from the study in the new analysis of the medication’s effectiveness in trial.

“We intend to continue the dialogue with the FDA to ensure that DCCR is approved for individuals with PWS as expeditiously as possible,” Anish Bhatnagar, MD, CEO of Soleno, said in a press release.

The FDA’s requirement for a new trial follows Soleno’s submission of that new analysis from the company-sponsored DESTINY PWS trial (NCT03440814). The updated findings showed that DCCR was significantly better than a placebo at easing excessive hunger — known as hyperphagia — and behavioral symptoms such as aggressiveness and anxiety in PWS patients.

Notably, the new data were acquired from pre-pandemic visits that occurred through March 1, 2020, when COVID-19 was declared a national emergency in the U.S.

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. The trial was completed last June.

Following treatment completion, 115 participants joined the C602 extension study (NCT03714373), in which all patients will receive the treatment for a maximum of three years.

The study’s main (primary) goal was to assess the changes in hyperphagia-related behavior, as assessed with a caregiver-filled questionnaire. Additional (secondary) goals included clinical improvements, based on a clinician-filled scale, and measurements of body fat.

While top-line data showed that the study failed to meet its main goal of significantly reducing hyperphagia, the analysis of pre-pandemic data showed that DCCR led to significant improvements in both primary and secondary goals. This suggests that the pandemic had a detrimental impact on the trial’s top-line results.

Compared with the placebo, DCCR led to a statistically significant easing of hyperphagia from Jan. 15 to the middle of March, after which significance was lost.

Significant reductions also were seen in behavioral problems, including aggressiveness, anxiety, rigidity, irritability, and compulsivity. Improvements in communication and social interactions also were found.

DCCR, an extended-release formulation tablet administered once daily, blocks the release of two appetite-stimulating proteins in the brain — neuropeptide Y and agouti-related protein — believed to play a role in hyperphagia.

“Based on the totality of data generated to date, we remain confident in DCCR’s potential to address the unmet need for a safe and effective treatment option for PWS patients,” Bhatnagar said.

“We are currently evaluating the appropriate next steps for our DCCR program,” he added.

Soleno recently partnered with Vanderbilt University to develop additional therapies for rare conditions with a similar working model to DCCR.