Proof-of-concept Study Shows DCCR Treatment Addresses Unmet Needs in PWS

Results of a Phase 2 clinical trial testing diazoxide chloride controlled release (DCCR) in people with Prader-Willi syndrome (PWS) showed the investigational therapy can address some unmet needs in this patient population — namely hyperphagia, or excessive appetite, and aggressive behavior.

The data were published in the journal PLOS One, in an article titled, “A randomized pilot efficacy and safety trial of diazoxide choline controlled-release in patients with Prader-Willi syndrome.”

DCCR, an investigational therapy being developed by Soleno Therapeutics, is an extended-release formulation of diazoxide, which is thought to help activate potassium channels on neurons that are underactive in people with PWS.

In the Phase 1/2 clinical trial (NCT02034071), 13 overweight or obese PWS patients — five female, eight male; average age of 15.5 years, ranging from 11 to 21 years old — received oral DCCR.

First, in a 10-week, open-label treatment period, participants were given increasing doses of DCCR — from 1.5 mg/kg to 5.1 mg/kg, or a maximum dose of 507.5 mg. This was followed by a 4-week double-blind, placebo-controlled treatment period.

During the open-label period, two participants dropped out of the study. One withdrew due to a treatment-related side effect (high blood sugar), and one due to an unrelated institutionalization due to a preexisting psychiatric condition.

Following the trial’s first stage, the remaining 11 participants were randomly assigned to continue treatment with either DCCR or a placebo for an additional four weeks.

Results showed that DCCR induced a significant decrease in hyperphagia, or excessive appetite — a hallmark of PWS — as early as two weeks into treatment. There was an average decrease of 3.31 on a Modified Dykens questionnaire, the results showed.

In participants who received lower doses of DCCR — 1.5 mg/kg or 2.4 mg/kg — these initial responses did not persist. However, in those who got higher doses of the medication — 3.3 mg/kg or 4.2 mg/kg — hyperphagia remained reduced throughout the open-label treatment period.

DCCR also reduced body fat in 75% of the participants who completed the open-label part of the trial. All participants — 100% — experienced an increase in lean body mass/fat mass ratio, meaning they had more muscle relative to the amount of fat they had.

The investigational therapy also affected behavior, the results showed. Instances of aggressive and violent behaviors, as well as self-harming behaviors, decreased significantly following the open-label treatment period.

“DCCR treatment appears to address various unmet needs associated with PWS, including hyperphagia and aggressive behaviors in this proof-of-concept study,” the researchers said.

“If the results were replicated in a larger scale study, DCCR may be a preferred therapeutic option for patients with PWS,” they added.

Overall, the results are in line with earlier data suggesting that DCCR treatments reduce body fat and hyperphagia in people with PWS.

“We are pleased that data from our Phase 2 trial of DCCR in PWS has been published in a prestigious peer-reviewed journal, PLOS One,” Anish Bhatnagar, MD, CEO of Soleno Therapeutics, said in a press release.

A Phase 3 trial testing DCCR in people with PWS, called DESTINY PWS (NCT03440814), is ongoing and is currently recruiting participants. For more information on enrollment, go here.

“Based on the results from this Phase 2 trial, we designed and initiated a Phase 3 clinical development program that includes DESTINY PWS. Importantly, enrollment remains on track for the availability of top-line data from DESTINY PWS in the first half of 2020,” Bhatnagar said.