Soleno files for US approval of DCCR for hyperphagia
Application follows positive data from open-label Phase 3 trial
Soleno Therapeutics is seeking approval of diazoxide choline controlled-release (DCCR) tablets in the U.S. for Prader-Willi syndrome (PWS) patients, 4 and older, with excessive hunger.
The filing of the new drug application with the U.S. Food and Drug Administration (FDA) follows positive data from an open-label extension Phase 3 clinical trial (NCT03714373) showing patients switching from DCCR to a placebo experienced worsening excessive hunger, or hyperphagia, compared with those who continued on DCCR treatment.
The trial’s four-month withdrawal period was introduced in 2022 to meet the FDA’s request for more clinical data to support that once-daily DCCR treatment may reduce hyperphagia and lead to changes in body composition that favor lean mass over fat.
The submission to the FDA “marks a significant milestone not only for Soleno, but for people living with PWS,” Anish Bhatnagar, MD, Soleno’s CEO, said in a company press release. “We look forward to working with the FDA throughout the review process.”
Soleno seeks 6-month priority review by FDA
If Soleno’s application is accepted and given priority by the FDA, as requested by the company, the agency has six months to decide, which is four months shorter than the standard 10-month review timeline.
For Bhatnagar, the submission is an “important step closer to our goal of bringing to market a new therapeutic for individuals with PWS that addresses the life-threatening hyperphagia and other key aspects of this serious and rare condition.”
DCCR has received orphan drug designation in the U.S. and the European Union, and fast track and breakthrough designations in the U.S. for PWS, all of which provide incentives to accelerate its clinical development and regulatory review.
Beginning in childhood, PWS manifests as constant hunger and an obsession with food that leads to a strong urge to eat and to being overweight or obese. This adds to a range of other symptoms such as learning difficulties, behavioral challenges, and problems with sleep.
DCCR prevents the release of neuropeptide Y and agouti-related protein — two brain molecules thought to drive hyperphagia — by activating, or keeping open, gate-like proteins called ATP-sensitive potassium (KATP) channels in the hypothalamus, a brain region.
When it acts on KATP channels in the pancreas, DCCR blocks the release of insulin, a hormone that helps sugar move from the blood into the body’s cells, which helps increase the amount of blood sugar and the feeling of satiety. It also reduces the buildup of fat.
Extended-release formulation allows once-daily dosing
Its extended-release formulation allows DCCR to be taken up into the bloodstream in a controlled way, beginning in the stomach and then continuing in the bowel. This helps maintain a steady amount of the medication in circulation with once-daily dosing.
A Phase 3 trial called DESTINY PWS or C601 (NCT03440814) tested the therapy against a placebo in 127 patients, 4 and older, who were recruited at sites in the U.S. and the U.K.
Top-line results showed the study failed to meet its main goal of showing that DCCR outperformed a placebo at easing hyperphagia. However, further analyses suggested the COVID-19 pandemic could have affected the outcomes.
Most (90.6%) of the patients who completed DESTINY PWS chose to enroll in the trial’s open-label extension trial, known as study C602, where all would receive DCCR for one year.
One year of treatment resulted in significantly less hyperphagia and behavioral challenges in these patients. Also, these reductions were significantly greater than those seen in untreated, matched patients participating in the PATH for PWS natural history study (NCT03718416).
Most caregivers report easing of behavioral symptoms
In addition, DCCR treatment was associated with caregiver-perceived improvements across several behavior domains, as well as in body composition, and metabolic and hormonal markers.
In response to the FDA’s call for more clinical data, the company started the withdrawal period in the C602 study, where patients were randomly assigned to either continue on DCCR or switch to a placebo. The switch was found to result in worsening hyperphagia and gains in weight and fat mass.
Eligible C602 study participants could choose to enter another open-label extension study, called C614 (NCT05701774), in which all will receive DCCR treatment for up to five years.
“We extend sincere gratitude to the team at Soleno, investigators, study site teams, advocacy organizations and most importantly, the individuals with PWS and their families who were instrumental in completing our DCCR development program,” Bhatnagar said.
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