New Trial for DCCR Still Favored by FDA, But Fresh Evidence Welcome

An additional clinical trial into diazoxide choline controlled release (DCCR) tablets as a potential treatment for the insatiable hunger associated with Prader-Willi syndrome (PWS) continues to be seen as necessary by U.S. Food and Drug Administration (FDA) to support a request for DCCR’s approval.

But the agency also encouraged Soleno Therapeutics, the potential therapy’s developer, to submit available safety and efficacy data from the DESTINY PWS Phase 3 trial (NCT03440814) — and its open-label extension study (NCT03714373, also called C602) — for its decision.

“We are continuing our dialogue with the FDA and remain focused on our goal of achieving approval for DCCR for the treatment of PWS,” Anish Bhatnagar, MD, Soleno’s CEO, said in a press release.

According to the company, the global COVID-19 pandemic affected DESTINY PWS results, causing top-line data to show  the investigational therapy failing to significantly ease hyperphagia, the uncontrollable hunger that is the hallmark symptom of PWS and the trial’s main goal.

An analysis conducted after those results were released, however, suggested that DCCR had, in fact, eased hyperphagia and several other PWS symptoms, including aggressiveness, anxiety, and irritability.

Bhatnagar, in a recent interview with Prader-Willi Syndrome News, explained that although most (80%) trial participants had completed the 13-week treatment period before the pandemic was declared a national emergency in the U.S., what followed that declaration appeared “to have had enough of an impact” on the remaining patients to affect measures of treatment benefit.

“The trend for improvement continued,” he said. “It just so happened that the p-value [a common threshold for statistical significance in a trial goal] was not significant.”

These findings, added to the unmet medical needs of PWS patients, led disease advocacy groups to ask the FDA to reconsider its request, and the delays in an approval process that would mean.

Recruiting enough eligible patients for another trial is a further challenge, given the rarity of PWS. It is unclear whether those who participated in DESTINY PWS would be eligible to take part in a new trial.

Jennifer Miller, MD, a lead trial investigator, described the effect that DCCR had on patients under her care as “life-changing.”

In a separate interview, Miller spoke of witnessing compulsive behaviors in patients dissipate, adding “I was blown away that a single drug could have the efficacy that [DCCR] has.”

Soleno met with the FDA’s Division of Diabetes, Lipids and Obesity on June 11. Also in attendance were PWS advocacy organizations to provide a “patient voice,” as well as the family of one of the trial’s participants.

“We appreciate the opportunity to include the patient voice in our discussions with the Division,” Bhatnagar said. “We intend to submit additional data from DESTINY PWS and the C602 extension study to the Agency” before the end of September.

“The FDA has agreed to review these data to determine if the totality of data generated to date are sufficient to support a potential [New Drug Application] submission,” he added.