Soleno Therapeutics has announced that the U.S. Food and Drug Administration (FDA) will proceed with its review of the company's New Drug Application (NDA) for diazoxide choline extended-release (DCCR) tablets without convening an advisory committee meeting at this stage. DCCR is under evaluation for the treatment of Prader-Willi syndrome (PWS). The FDA's decision streamlines the review process, keeping the final decision date on track for December 27.
Regulatory Pathway and Designations
The FDA's decision not to hold an advisory committee meeting suggests a level of confidence in the data package submitted by Soleno. However, the agency retains the option to convene a meeting later in the review cycle if deemed necessary. DCCR has already been granted priority review, which shortens the review timeline from ten to six months, as well as orphan drug, fast track, and breakthrough therapy designations in the U.S. and orphan drug status in the European Union. These designations are designed to expedite the development and review of treatments for rare diseases.
Prader-Willi Syndrome and Unmet Needs
PWS is a rare genetic disorder affecting approximately 1 in 15,000 live births. Key characteristics include hyperphagia, a persistent and insatiable appetite, leading to obesity and related complications. According to the Foundation for Prader-Willi Research, 96.5% of caregivers consider hyperphagia a critical symptom to address. Currently, no approved therapies specifically target hyperphagia in PWS, representing a significant unmet medical need.
DCCR: Mechanism of Action and Clinical Trials
DCCR is a once-daily, extended-release formulation of diazoxide choline designed to mitigate hyperphagia and other PWS symptoms. The drug is believed to work by modulating specific proteins in the brain and pancreas, potentially reducing appetite, increasing satiety, and decreasing fat accumulation. While diazoxide has been used to treat some rare diseases, DCCR is specifically formulated for PWS.
The DCCR development program includes multiple Phase 1, Phase 2, and Phase 3 clinical trials. The pivotal Phase 3 DESTINY PWS trial (NCT03440814) enrolled 127 patients aged 4 years and older. While the trial did not meet its primary endpoint of statistically significant reduction in hyperphagia compared to placebo, it suggested potential benefits in reducing aggressive behaviors and improving metabolic parameters. Notably, Soleno has suggested that the COVID-19 pandemic may have impacted trial results.
Open-Label Extension Study and Withdrawal Period
Following an FDA request for additional data, Soleno conducted a four-month withdrawal period within the DESTINY PWS open-label extension study C602 (NCT03714373). Patients were randomized to either switch to placebo or continue DCCR treatment. Results indicated that patients who switched to placebo experienced a worsening of hyperphagia and weight gain, providing further evidence supporting DCCR's potential efficacy.
