Once Prader-Willi patients reach the stage where hyperphagia is a dominant characteristic of the disease, the progression to obesity, morbid obesity and diabetes and their complications reduces the quality of life of the patient and increases their risk of death from a number of causes. The constant food seeking and food obsession combined with the patients difficult to manage behavior contribute to reductions in the quality of life of the caregiver and family and to stress on the patient’s siblings.
Based on what we know about how diazoxide choline controlled-release tablet (DCCR) works to control appetite and to increase energy expenditure, treatment of Prader-Willi syndrome patients with DCCR should reduce their appetite, increase their energy expenditure and limit the progression to morbid obesity and diabetes. This treatment also has the potential to limit some of the more difficult to manage behaviors. Our insight into how the drug works comes from studies in cultured cells and tissues, from work in many animal models, from results of treatment of a limited number of PWS patients and from a number of other clinical studies.
Diazoxide, the parent molecule of DCCR, has been safely used to treat a number of orphan diseases for more than 30 years. This use is at much higher doses than required for PWS. This clinical study is designed to evaluate the safety of 5 dose levels of DCCR in PWS patients, and to provide evidence of the impact of DCCR on hyperphagia and other characteristics of the disease. Patients will be treated with DCCR for a minimum of 12 weeks and a maximum of 16 weeks. Once the results of this clinical study are available, Essentialis, the developer of DCCR, will be able negotiate with the FDA what other clinical studies are needed to support approval in PWS.
A randomized pilot efficacy and safety trial of diazoxide choline controlled-release in patients with Prader-Willi syndrome. Kimonis V, Surampalli A, Wencel M, Gold JA, Cowen NM. PLoS ONE. 2019. 14(9): e0221615.
Neil Cowen, PhD, MBA