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Abstract Details

Ataluren Delays Clinically Meaningful Milestones of Decline in 6WMD in Patients with nmDMD from Study 041, a Phase 3, Placebo-controlled Trial
Neuromuscular and Clinical Neurophysiology (EMG)
S21 - Inherited Myopathies and Neuropathies: New Therapeutic Approaches and Observations (1:00 PM-1:12 PM)
001

Persistent 10% or 5% worsening and a 30m decline in 6-minute walk distance (6MWD) have been established as clinically meaningful milestones of disease progression in patients with DMD.

To assess the effects of ataluren in clinically meaningful milestones in Duchenne muscular dystrophy (DMD).

Study 041 (NCT03179631) is an international, phase 3, randomized, double-blind, placebo-controlled 72-week ataluren trial followed by a 72-week open-label period. Eligible boys with genetically confirmed nonsense mutation DMD (nmDMD), aged ≥5 years and with a 6MWD ≥150m were randomized 1:1 to receive ataluren/placebo. The intention-to-treat population comprised boys who received ≥1 dose of study treatment. Predefined subgroups included patients with baseline 6MWD 300–400m, and patients with baseline 6MWD ≥300m and stand from supine ≥5s (primary analysis subgroup). Decline in 6MWD over 72 weeks was assessed in these populations.

In the intention-to-treat population (ataluren, n=183; placebo, n=176), ataluren significantly reduced the risk of persistent 10% and 5% worsening in 6MWD by 31% (p=0.0078) and 30% (p=0.0082), respectively, and 30m decline by 31% (p=0.0067), vs placebo. In the 6MWD 300–400m subgroup, ataluren significantly reduced the risk of persistent 10% and 5% worsening in 6MWD by 47% (p=0.0011) and 42% (p=0.0029), respectively, and 30m decline by 47% (p=0.0009), vs placebo. In the primary analysis subgroup, there was a reduced risk of 10% persistent worsening in 6MWD for patients treated with ataluren compared with placebo, this did not reach statistical significance (p=0.0659).

These results indicate that ataluren delays clinically meaningful milestones of nmDMD progression that predict ambulatory decline.

Authors/Disclosures
Jeffrey Statland (University of Kansas Medical Center)
PRESENTER
Dr. Statland has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arrowhead. Dr. Statland has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ML Bio. Dr. Statland has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MT Pharma. Dr. Statland has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Epic Bio. Dr. Statland has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Armatus . Dr. Statland has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Dyne Therapeutics. Dr. Statland has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avidity . Dr. Statland has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Fulcrum Therapeutics. Dr. Statland has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. The institution of Dr. Statland has received research support from NIH. The institution of Dr. Statland has received research support from FSHD Society. The institution of Dr. Statland has received research support from Friends of FSH Research. The institution of Dr. Statland has received research support from FSHD Canada. The institution of Dr. Statland has received research support from MDA.
No disclosure on file
Sheffali Gulati (All India Institute of Medical Sciences) Prof. Gulati has nothing to disclose.
No disclosure on file
Rosa Escobar Cedillo Rosa Escobar Cedillo has nothing to disclose.
Anna Kostera-Pruszczyk (Warszawski Uniwerystet Medyczny) No disclosure on file
No disclosure on file
Kazuhiro Haginoya (Miyagi Children'S Hospital) Dr. Haginoya has nothing to disclose.
Vinay Penematsa Vinay Penematsa has nothing to disclose.
No disclosure on file
No disclosure on file
No disclosure on file