Optimizing Prader-Willi Syndrome Clinical Trials

By Joan Busner, PhD, Lew Fredane, MD, & Pascal Goetghebeur

Prader-Willi syndrome (PWS) is a rare genetic disorder affecting 1 in 20,000-30,000 individuals worldwide. Recombinant human growth hormone is the only FDA-approved treatment for PWS but does not address hyperphagia or other core symptoms. Currently, no approved therapies exist for hyperphagia, behavioral challenges, or sleep issues. Seventeen PWS clinical trials are underway, including one for diazoxide choline (DCCR), an investigational product (IP) from Soleno Therapeutics. DCCR has shown promise in managing hyperphagia and related symptoms, receiving Breakthrough and Orphan Drug Designations from the FDA and EU. Its regulatory review is ongoing following the FDA’s acceptance of the New Drug Application (NDA) in August 2024. Clinical trial success hinges on the safety and efficacy of the IP but is often challenged by placebo effects, biases, and data variability. Signant’s approach includes comprehensive rater training, use of electronic scales, data quality monitoring, and strategies to mitigate placebo responses. These measures aim to ensure high-quality data and improve the chances of success in PWS clinical trials.