Diazoxide choline controlled-release tablet is a novel, proprietary extended-release, crystalline salt formulation of diazoxide, which is administered once-daily. The parent molecule, diazoxide, has been used for decades in thousands of patients in a few rare diseases in neonates, infants, children and adults, but has not been approved for use in PWS. Soleno conceived of and established extensive patent protection on the therapeutic use of diazoxide and DCCR in patients with PWS. The DCCR development program is supported by data from five completed Phase I clinical studies in healthy volunteers and three completed Phase II clinical studies, one of which was in PWS patients. In the PWS Phase II study, DCCR showed promise in addressing hyperphagia, the hallmark symptom of PWS, as well as several other symptoms such as aggressive/destructive behaviors, fat mass and abnormal lipid profiles.
Soleno has assembled an extensive toxicological package on the product which shows a wide margin of safety for therapeutically relevant doses.
The safety profile of diazoxide is well known, with more than 100,000 patient years of use. DCCR has been tested in 8 clinical trials involving nearly 300 randomized patients including more than 210 treated with DCCR. There have been no new safety findings with DCCR that had not previously been observed with diazoxide.
DCCR is an investigational product and has not been approved for use except in clinical trials by any health authority.
Diazoxide choline has received an orphan drug designation from US FDA as well as the European Medicines Agency (EMA) for the treatment of Prader-Willi syndrome.
In July of 2018 the FDA the DCCR development program in PWS a Fast Track Designation. This Designation allows additional meetings with the FDA to discuss DCCR’s development plan to ensure the appropriate data are collected and encourages frequent written communication with the FDA regarding design of clinical trials and use of biomarkers. If certain criteria are met, DCCR will be eligible for Accelerated Approval and Priority Review and also Rolling Submission, which allows Soleno to submit to the FDA sections of its New Drug Application (NDA) as they are finished instead of waiting for all sections to be completed before submitting the marketing application.