Endocrine Abstracts

JOINT1568

Background: Prader-Willi syndrome (PWS) is a rare genetic neurobehavioural-metabolic disorder characterised by hyperphagia and behavioural/psychological complications. No approved therapy exists for treating hyperphagia in patients with PWS. DCCR is an oral, once-daily medication currently under development for treating patients with PWS who have hyperphagia.

Objective: The objective of this analysis was to characterise the long-term efficacy of DCCR on DBC2 questionnaire total and subscale scores and the relationship between changes in behaviours and changes in hyperphagia in participants with PWS from 2 completed studies encompassing>3 years of exposure to DCCR.

Methods: The population included 125 participants ≥4 years old with genetically-confirmed PWS who received DCCR in either of 2 sequential studies: a 13-week, placebo-controlled study (Study C601) followed by an open-label extension (OLE) study (Study C602-OLE). Baseline was defined as the last assessment prior to the first DCCR dose. The primary endpoint was change from baseline in hyperphagia assessed by Hyperphagia Questionnaire for Clinical Trials (HQ-CT) Total Score. Behavioural changes were assessed using the DBC2 questionnaire which evaluates behaviours using total score and 6 subscales: Anxiety, Communication Disturbance, Disruptive Behaviour, Self-Absorbed, Social Relating and a subscale associated with PWS. The relationship between change in HQ-CT and changes in behaviour were evaluated using correlations.

Results: At baseline, the median age of participants was 12.0 (range 4, 44) years, 69 (55.2%) were female, and the mean (SD) HQ-CT Total Score was 21.5 (6.7). Over 3 years of DCCR administration, there was a clinically and statistically significant improvement in HQ-CT total score at all assessments [LS mean change (SE, n) at 3 years -10.7 (0.76; 81); P<0.0001]. Administration of DCCR was also associated with significant improvements in DBC2 total score at all timepoints [LS mean change (SE, n) at 3 years -15.5 (2.06, 71); P<0.0001] and all subscales at all timepoints (all P<0.0001). At 3 years, improvements in DBC2 subscale scores ranged from 29% to 39%. The correlation between HQ-CT change and DBC2 total score change at 52 weeks was 0.53 (P<0.0001), and the correlations between HQ-CT changes and changes in DBC2 subscales ranged from 0.25 (P=0.0159, anxiety subscale) to 0.56 (P<0.0001, self-absorbed subscale).

Conclusions: Long-term administration of DCCR for up to 3 years in participants with PWS was associated with clinically significant improvements in hyperphagia and behaviours. Behavioural improvements appeared to be independent of hyperphagia improvements. These hyperphagia and behavioural improvements should benefit patients with PWS and their families.