(147) Expected vs observed mortality rates, expressed as number needed to treat, from a Phase 3 clinical trial program of patients with hyperphagia and Prader-Willi Syndrome treated with diazoxide choline extended release (DCCR)

Background: : Prader-Willi syndrome (PWS) is a rare genetic disorder, characterized by hyperphagia, with a median age of death of 23 years and annual mortality rates ranging from 1.4% to 5.4% based on age group (McCandless 2020). Butler (2017) concluded that individuals with PWS show heightened hyperphagia-related mortality. The DCCR phase 3 program began with the C601 trial followed by the C602 open-label extension (C602-OLE) period to evaluate the safety and efficacy of DCCR treatment of hyperphagia in PWS. The observation period allowed for long-term safety monitoring.

Objective: : This analysis examines the mortality rate observed during the combined duration of C601 and C602-OLE studies to determine the Number Needed to Treat (NNT) to avoid an adverse health outcome, in this case death.

Methods: : The observed mortality rate was obtained from the C601 and C602-OLE studies. All patient-time exposure to DCCR for patients enrolled in C602-OLE was examined (includes exposure in C601). The expected mortality rate for PWS was obtained from an epidemiology study (McCandless 2020). Event rates were calculated from both sources and the absolute risk reduction rate and NNT were computed.

Results: : The C602-OLE study included 115 patients, age 4-44 years at baseline, who contributed a total of 313.4 patient years (median DCCR exposure 3.0 years; max 4.5 years). The observed mortality rate was 0 (event rate = 0%) on DCCR while the number of expected deaths was 7 (event rate = 2.23%). These rates yield a NNT of 45.

Conclusions: : PWS is a rare condition with many unmet needs and associated with an elevated mortality rate. Patients treated with DCCR did not experience a mortality event through up to 4.5 years of continued exposure. Given the epidemiologically expected mortality rate, the resulting NNT suggests that treating patients with DCCR may also reduce mortality events.

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