Background: Respiratory morbidity and hospitalization rates in patients with DMD increase as respiratory function declines. Idebenone reactivates and protects mitochondria, thus preserving muscle cell function. It significantly reduced the rate of respiratory function decline and morbidity vs placebo in steroid-naïve DMD patients in the phase III DELOS study.
Objectives: We investigated if reductions in bronchopulmonary adverse events (BAE), antibiotic use, and hospitalizations seen in the DELOS study were maintained with long-term idebenone treatment.
Approach: Data were analyzed from patients from the 12-month DELOS study and those patients from DELOS who entered the long-term SYROS study under Expanded Access Programs following a variable untreated period.
Results: In DELOS (n=64, mean [SD] age 14.3 [2.7] yrs; FVC%p 53.8 [11.8]), 19.4% of patients treated with idebenone had BAEs vs 51.5% in the placebo arm (82 vs 222 cumulative days, respectively). Systemic antibiotics were used in 22.6% of idebenone-treated and 39.4% of placebo patients. One idebenone-treated patient was hospitalized (3 days) vs 4 placebo patients (total 30 days). SYROS collected data from 18/64 DELOS patients (at DELOS baseline: mean [SD] age 13.3 [2.7] yrs; FVC%p 58.7 [17.6]), of which 11/18 patients were untreated prior to SYROS. To measure treatment effects on BAEs, event rates/person years (e/py) were compared for on- vs off-idebenone periods. Over ~6 years of follow-up (DELOS+SYROS ), patients were on idebenone for a mean (range) of 4.2 (2.4–6.1) yrs and off idebenone for 2.1 (1.1–5.5) yrs. While on idebenone, patients had fewer BAEs (0.10 vs 0.33 e/py), fewer systemic antibiotics (0.04 vs 0.15 e/py), and fewer hospitalizations due to BAEs (0.06 vs 0.15 e/py) or any reason (0.29 vs 0.48 e/py), compared with periods without treatment.
Conclusions: Cumulative data show that patients who were treated with long-term idebenone had a reduced rate and risk of BAEs, antibiotic use, and hospitalizations.