Idebenone Reduces Loss of Respiratory Function in Duchenne Muscular Dystrophy: Outcome of a Phase III Double Blind, Randomized, Placebo-Controlled Trial

G. Buyse; T. Meier

doi:10.1055/s-0035-1550668

Neuropediatrics, Table of Contents

Idebenone Reduces Loss of Respiratory Function in Duchenne Muscular Dystrophy: Outcome of a Phase III Double Blind, Randomized, Placebo-Controlled Trial

G. Buyse ¹, T. Meier ²

¹University Hospitals, Leuven, Belgium
²Santhera Pharmaceuticals, Liestal, Switzerland

Abstract

Aims: Cardiorespiratory failure is the leading cause of death in duchenne muscular dystrophy (DMD). Following preclinical and phase II evidence, efficacy and safety of Idebenone were assessed in a multicenter phase III trial in 10- to 18-year-old DMD patients not taking concomitant glucocorticosteroids (DELOS, ClinicalTrials.gov NCT01027884).

Methods: Patients were randomized 1:1 to receive Idebenone (Raxone/Catena) 900 mg/d or placebo for 52 weeks. The primary end point was change in peak expiratory flow % predicted (PEF%p) from baseline to week 52. Secondary respiratory outcome measures included forced vital capacity (FVC), forced expiratory volume in the first second of expiration (FEV₁), weekly home-based PEF measurements, peak cough flow (PCF), and maximal mouth pressures. A mixed model for repeated measurements was used for efficacy analyses. The ITT population consisted of 64 patients (31 Idebenone and 33 placebo). A modified ITT population (mITT) was prospectively defined excluding seven patients.

Results: Idebenone significantly reduced the decline in PEF%p in the mITT (primary end point: decline in PEF% p of 3.05%p for Idebenone vs. 9.01%p for placebo, week 52 treatment effect of 5.96%p; p = 0.04) and ITT population (2.57%p vs. 8.84%p, week 52 treatment effect of 6.27%p; p = 0.03). A significant Idebenone effect was also observed in PEF (L/min), weekly home-based PEF as well as analyses of FVC and FEV₁. The effect of Idebenone on PEF%p, FVC%p, and FEV1%p were comparable between patients with previous corticosteroid use and steroid naive patients. Results of respiratory function analyses were supported by responder analyses and clinical observations. No significant differences were observed in maximal mouth pressures and PCF. Treatment with Idebenone was safe and well tolerated.

Conclusion: The data showed that Idebenone was safe and well tolerated, significantly reduced loss of respiratory function, and represents a new treatment option for patients with DMD.

Keywords: duchenne muscular dystrophy, Idebenone, steroids.