Evaluation of Efficacy and Safety Baseline Parameters in Patients with Duchenne Muscular Dystrophy (DMD) from Three Placebo-Controlled Studies of Drisapersen (DRIS) (P6.255)

OBJECTIVE: DRIS (6mg/kg/wk) showed clinically meaningful and statistically significant effects in one Phase II study (DMD114117 [117]), clinically meaningful but not statistically significant effects in another Phase II study (DMD114876 [876]) and neither clinically meaningful nor statistically significant effects in a Phase III study (DMD114044 [044]), although there was a benefit for 6-minute walking distance (6MWD) of 21m in a subset of boys ≤7y; baseline (BL) demographics and clinical characteristics of boys in these studies were compared to better understand these findings. BACKGROUND: DMD is a rare condition; therefore, the study populations were small (51-186 subjects). DESIGN/METHODS: Three placebo (PBO)-controlled studies (24-48 wks), each with a primary endpoint of 6MWD. RESULTS: Although mean ages for each study were similar, in 044, boys were older with a longer time since first diagnosis and treatment. Study populations differed with respect to disease severity at BL. Notably, patients from 044 had lower BL 6MWD than patients from 876 or 117: 337 and 348m for DRIS and PBO arms, respectively, versus 396 and 416m (876) and 428 and 403m (117). Similarly, rise from floor time was slower at BL for patients from 044 than from the other two studies: 12.3 and 13.4s for DRIS and PBO arms, respectively, versus 5.2 and 4.5s (876) and 4.8 and 4.7s (117). For some BL safety parameters (e.g. urinary protein, albumin and α1-microglobulin), a small proportion of boys had values above the high range of normal at screening. CK, LFTs were elevated as expected in this population. CONCLUSIONS: BL parameters suggest that boys in 044 may have had a poorer prognosis and may be more likely to experience substantial deterioration in gross motor skills and ambulatory capacity. These findings are important to understand the different outcomes in the three DRIS PBO-controlled studies. Studies Supported by: GlaxoSmithKline Disclosure: Dr. Campion has received personal compensation for activities with Prosensa Therapeutics as an employee. Dr. Voit has received personal compensation for activities with Prosensa. Dr. Goemans has nothing to disclose. Dr. Wilson has received personal compensation for activities with Prosensa as a consultant. Dr. Wardell has nothing to disclose. Dr. McDonald has received personal compensation for activities with PTC Therapeutics and Sarepta Therapeutics as an advisory board participant and/or consultant.