Dados do Trabalho

Título

ATALUREN PRESERVES UPPER LIMB FUNCTION IN NMDMD PATIENTS FROM STUDY 041, A PHASE 3 PLACEBO-CONTROLLED TRIAL, AND THE STRIDE REGISTRY

Introdução

We assessed performance of upper limb (PUL) function in nonsense mutation Duchenne muscular dystrophy (nmDMD) patients receiving ataluren+standard of care (SoC) in Study 041 (NCT03179631), a phase 3, double-blind, placebo-controlled 72-week trial, and in the STRIDE Registry (NCT02369731), an ongoing, long-term, real-world evidence study.

Objetivo

We assessed performance of upper limb (PUL) function in nonsense mutation Duchenne muscular dystrophy (nmDMD) patients receiving ataluren+standard of care (SoC) in Study 041 (NCT03179631), a phase 3, double-blind, placebo-controlled 72-week trial, and in the STRIDE Registry (NCT02369731), an ongoing, long-term, real-world evidence study.

Método

In Study 041, nmDMD boys aged ≥5 years, on a stable corticosteroid regimen, and with a 6-minute walk distance (6MWD) ≥150m were randomized 1:1, ataluren: placebo. The intentionto-treat (ITT) population comprised randomized boys who received at least one dose of
study treatment (N=359; mean age 8.1 years); a key subgroup included those with baseline 300-400m 6MWD (n=169). STRIDE patients were propensity-score matched to patients receiving SoC alone in CINRG DNHS (NCT00468832), yielding a comparable population (N=261). Kaplan-Meier analyses estimated age at loss of upper limb function.

Resultados e Conclusões

Least-squares mean PUL total score change from baseline to week 72 (by MMRM analysis) numerically favored ataluren vs placebo (0.44, p=0.1059) in the Study 041 ITT population and was significant in the 300–400m 6MWD subgroup (1.02, p=0.0165). Inmatched STRIDE vs CINRG patients (mean last assessment age, 13.1 vs 14.6), ataluren preserved hand-to-mouth function by 3.4 years (p=0.0046) as assessed by entry level items of PUL vs Brooke Scale, respectively. Median age at loss of overhead reach numerically favored STRIDE, consistent with the overall trend (15.8 vs 12.6; p=0.2872). Median age at loss of distal hand function was non-estimable for STRIDE patients. Results indicate that ataluren may help preserve upper limb function in advanced nmDMD patients.

Palavras Chave

Duchenne muscular dystrophy, nonsense mutation, upper limb function.

Declaração de conflito de interesses de TODOS os autores

CMMhas acted as a consultant on clinical trials of DMD for Astellas, Capricor, Catabasis, Edgewise Therapeutics, Epirium Bio (formerly Cardero Therapeutics), FibroGen, Italfarmaco, Pfizer, PTC Therapeutics, Santhera Pharmaceuticals and Sarepta Therapeutics. He has received research support for clinical trials from Capricor, Catabasis, Italfarmaco, Pfizer, PTC Therapeutics, Santhera Pharmaceuticals and Sarepta Therapeutics.

APC, DSM, AF and PT are employees of PTC Therapeutics.