Soleno’s DCCR under FDA priority review for hyperphagia in PWS
FDA decision expected by Dec. 27
The U.S. Food and Drug Administration (FDA) will review Soleno Therapeutics’ application seeking approval of its extended-release formulation of diazoxide choline (DCCR) for Prader-Willi syndrome (PWS) in patients, 4 and older, with excessive hunger.
The new drug application (NDA), filed in July, was granted priority review, shortening the review process to six months from the standard 10 months. The FDA plans to hold a meeting with an advisory committee that could help decide if DCCR should be approved, and a decision is expected by Dec. 27.
“PWS is a devastating, rare condition that significantly impacts the lives of patients and their families,” Anish Bhatnagar, MD, Soleno’s CEO, said in a company press release. “The FDA’s acceptance of our NDA is a significant milestone, and designating our application for priority review reaffirms that the FDA views PWS as a serious condition.”
PWS causes a constant feeling of hunger, or hyperphagia, leading to excessive eating and being overweight or obese during childhood. The disease is also characterized by a short stature and a range of other symptoms that include learning difficulties and behavioral challenges such as temper outbursts.
DCCR acts on gate-like proteins called ATP-sensitive potassium (KATP) channels. By keeping KATP channels open in certain nerve cells responsible for the production of appetite-driving molecules, DCCR was shown to reduce appetite in animal models of PWS.
DCCR suppresses release of insulin in pancreas
In the pancreas, DCCR suppresses the release of insulin, a hormone that helps glucose, or blood sugar, move from the blood into cells in the body. Blocking the release of insulin keeps more glucose in the blood, which increases the feeling of fullness and reduces the buildup of fat in tissues.
The extended-release formulation in oral tablets was developed such that it releases DCCR slowly, starting in the stomach and continuing in the bowel, ensuring steady levels in the blood with one daily dose.
DCCR has received fast track and breakthrough designations in the U.S. and orphan drug designation in the U.S. and the European Union for PWS. Such designations provide the company with incentives to accelerate DCCR’s clinical development.
The Phase 3 DESTINY PWS clinical trial (NCT03440814), enrolled 127 PWS patients, 4 and older, at sites in the U.S. and the U.K. The study failed to show that DCCR was better than a placebo for reducing hyperphagia, but COVID-19 may have influenced the results.
Most patients (90.6%) chose to continue taking DCCR in an open-label extension study, called study C602 (NCT03714373), where one year of treatment led to less hyperphagia and fewer behavioral challenges.
In response to the FDA’s request for more data, the company implemented a four-month withdrawal period in study C602, in which patients either switched to a placebo or continued their daily treatment with DCCR. Those who switched experienced worsening hyperphagia and weight gain, data that helps to support the NDA.
“We are immensely grateful to the entire PWS community, including patients, caregivers and advocacy groups, for their ongoing support,” Bhatnagar said. “We remain committed to continuing to work closely with the FDA through the NDA review process.”
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