RF24 | PSUN94 Long-Term Safety of Diazoxide Choline Extended-Release (DCCR) Tablets in Patients with Prader-Willi Syndrome

Abstract Background Prader-Willi syndrome (PWS), a rare genetic neurobehavioral-metabolic condition, is characterized by hyperphagia, accumulation of excess fat, hypotonia, and behavioral/psychological complications. There are no currently approved medications to treat hyperphagia in patients with PWS; DCCR is under development as a treatment for PWS. Objectives and methods The objective was to evaluate long-term safety of DCCR in individuals with PWS. 125 participants with genetically-confirmed PWS ≥4 years old with hyperphagia were treated with oral daily DCCR in multi-center studies conducted at 29 sites in the US and the UK: a 13-week, Phase 3, double-blind, placebo-controlled study (DESTINY PWS) and its long-term, open-label extension study (to 52 weeks and beyond). Enrolled participants had hyperphagia assessed by the Hyperphagia Questionnaire for Clinical Trials (HQ-CT). The target DCCR dose was ≥3.3 mg/kg (optimal dose 4.2 - 5.8 mg/kg). 103 patients received DCCR for 52 weeks and 54 patients received DCCR for at least 78 weeks. Results Overall, DCCR was well tolerated with the majority of adverse events (AEs), (77.6%) having grade 1 or 2 severity. Treatment-emergent adverse events (TEAEs) occurred in 98.4% of participants. Drug related TEAEs occurred in 80.0% of participants. Twenty participants experienced serious adverse events (SAEs), for which only two participants were considered drug related (one patient with peripheral/pulmonary edema and another with fluid retention). There were no Suspected Unexpected Serious Adverse Reactions (SUSARs) or SAEs leading to death. The most common TEAEs were hypertrichosis (61.6%), peripheral edema (34.4%), and hyperglycemia (22.4%). TEAEs infrequently resulted in discontinuation of study drug (7.2% of participants). These results are consistent with the observed safety profile of DCCR from prior studies. Consistent with the expected AE of hyperglycemia, fasting glucose rose through Week 26 (mean change from baseline ± SD mmol/L = 0.35±0.81) and returned nearly to baseline by 15 months of treatment (0.11±0.61). HbA1c followed a similar pattern, increasing at 26 weeks (mean change from baseline ± SD % = 0.19±0.50) and returning nearly to baseline by 15 months (0.03±0.38). In participants experiencing hyperglycemia, the AE resolved with continued treatment in about half of cases. Four participants experienced recurrent hyperglycemia. About 90% of cases of peripheral edema resolved while treatment continued, requiring infrequent dose adjustment (7%) or the need for diuretic treatment (3%). Most cases of hypertrichosis (>80%) were mild and only in one instance led to discontinuation. About 35% of cases of hypertrichosis were resolved/resolving at Week 52. Conclusions DCCR was well tolerated beyond 52 weeks of administration. The most common treatment-emergent adverse events were expected based on prior studies of DCCR. These included hypertrichosis, peripheral edema and hyperglycemia, which were typically mild and resolved without treatment in most cases. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Sunday, June 12, 2022 12:54 p.m. - 1:59 p.m.