Soleno Therapeutics has announced that the U.S. Food and Drug Administration (FDA) has accepted for filing its New Drug Application (NDA) for DCCR (diazoxide choline) extended-release tablets for the treatment of Prader-Willi syndrome (PWS) in patients four years and older who experience hyperphagia. The FDA granted Priority Review for the NDA, setting a Prescription Drug User Fee Act (PDUFA) target action date of December 27, 2024. The FDA also plans to hold an advisory committee meeting to discuss the application.
Clinical Significance
Priority review is reserved for drugs that, if approved, would significantly improve the safety or effectiveness of the treatment, prevention, or diagnosis of a serious condition. Anish Bhatnagar, M.D., CEO of Soleno, stated that the FDA's acceptance of the NDA and the priority review designation reaffirm the view that PWS is a serious condition.
Prader-Willi Syndrome and Hyperphagia
Prader-Willi Syndrome is a rare genetic disorder affecting an estimated 1 in 15,000 live births. A hallmark symptom is hyperphagia, characterized by a persistent, intense hunger, preoccupation with food, and an extreme drive to seek and consume food. This can severely diminish the quality of life for individuals with PWS and their families. Additional characteristics include behavioral problems, cognitive disabilities, low muscle tone, short stature, excess body fat, developmental delays, and incomplete sexual development. Hyperphagia can lead to significant mortality and comorbidities such as diabetes, obesity, and cardiovascular disease. According to a global survey by the Foundation for Prader-Willi Research, 96.5% of caregivers rated hyperphagia as the most important symptom to be relieved by a new medicine.
DCCR: Mechanism of Action and Clinical Development
DCCR (diazoxide choline) is a novel, proprietary extended-release formulation administered once daily. Diazoxide choline acts on ATP-sensitive potassium (KATP) channels, keeping them open in nerve cells responsible for producing appetite-driving molecules, which has been shown to reduce appetite in animal models of PWS. In the pancreas, DCCR suppresses insulin release, maintaining higher blood glucose levels, which increases the feeling of fullness and reduces fat buildup. The extended-release formulation ensures steady blood levels with a once-daily dose.
DCCR has received Breakthrough and Fast Track Designations in the U.S., as well as Orphan Drug Designation for PWS in the U.S. and E.U.
The Phase 3 DESTINY PWS clinical trial (NCT03440814) enrolled 127 PWS patients aged four and older. While the study did not meet its primary endpoint of reducing hyperphagia compared to placebo, Soleno has stated that the COVID-19 pandemic may have influenced the results. A subsequent open-label extension study (NCT03714373) showed that one year of DCCR treatment led to less hyperphagia and fewer behavioral challenges. Data from a withdrawal period in the extension study, where patients switched to placebo, further supported the NDA, with those patients experiencing worsening hyperphagia and weight gain.
Looking Ahead
With the FDA's priority review and planned advisory committee meeting, Soleno Therapeutics is working towards potential approval of DCCR. If approved, DCCR could become the first therapy to treat the hyperphagia and related metabolic and behavioral aspects of Prader-Willi Syndrome, addressing a significant unmet medical need.
