DCCR now under review in EU as hyperphagia treatment in PWS
Soleno approval application for extended-release therapy validated by EMA
The extended-release formulation of diazoxide choline (DCCR) — approved in the U.S. earlier this year for use in Prader-Willi syndrome (PWS) — is now under review in the European Union as a treatment for hyperphagia, or insatiable hunger, in PWS patients ages 4 and older, according to its developer Soleno Therapeutics.
Soleno announced that the European Medicines Agency (EMA), which authorizes medications for use in the EU, has validated its application seeking approval of DCCR. The EMA’s validation process ensures that a request for approval — here, submitted as a marketing authorization application (MAA) — is complete and contains all the necessary information to begin an evaluation.
“The validation of our MAA represents the next significant milestone in our mission to deliver this important therapy to the broad PWS community, including those in the EU,” Anish Bhatnagar, MD, chairman and CEO of Soleno, said in a company press release. “We look forward to working closely with European regulators during the review process and intend to make DCCR available to patients in the EU as expeditiously as possible, if approved.”
The once-daily oral therapy was approved by the U.S. Food and Drug Administration for the same indication in March under the brand name Vykat XR. It became available in the U.S. less than a month later.
DCCR approved in US under brand name Vykat XR
A rare neurodevelopmental disorder, PWS is caused by missing or defective genes in a particular region of chromosome 15. Hyperphagia is a defining symptom of PWS, which typically emerges between the ages of 1 and 4.
Patients with hyperphagia always feel an intense hunger accompanied by preoccupations with food, an extreme desire to eat, food-related behavior problems, and an inability to feel full after eating. Excessive eating can lead to long-term health problems such as diabetes, obesity, and cardiovascular disease.
DCCR works by activating proteins that act like gates, called ATP-sensitive potassium channels, that open and close based on the amount of glucose, or blood sugar, in the bloodstream.
By keeping these channels open, the therapy is expected to ease hyperphagia by suppressing the release of appetite-stimulating molecules that are thought to drive the symptom.
The therapy also blocks the pancreatic release of insulin, a hormone that regulates the flow of glucose from the bloodstream into cells. Lower insulin levels mean more glucose stays in the bloodstream, boosting the feeling of satiety and preventing the buildup of excess fat.
With the extended-release formulation, DCCR levels in the bloodstream remain stable over a one-day period, allowing for a single, daily dose taken by mouth.
Based on the data generated, DCCR has the potential to help treat hyperphagia, which is the most life-limiting aspect of PWS.
Soleno’s application to the EMA contains data from the Phase 3 DESTINY PWS clinical trial (NCT03440814) and its open-label extension study (NCT03714373). DESTINY PWS tested the therapy in 127 patients, ages 4 and older.
While DCCR failed to outperform a placebo in easing hyperphagia in DESTINY PWS, the researchers found that hyperphagia and associated behavioral symptoms were significantly reduced after one year of treatment in the extension study.
Moreover, patients who switched from DCCR to a placebo in a following four-month withdrawal period had worse hyperphagia compared with those who remained on treatment. In a subsequent extension study, called C614 (NCT05701774), those restarting DCCR treatment experienced sustained hyperphagia reductions.
“Based on the data generated, DCCR has the potential to help treat hyperphagia, which is the most life-limiting aspect of PWS,” Bhatnagar said.
Per the release, about 9,500 people altogether in France, Germany, Italy, Spain, and the U.K. have PWS.
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