Idebenone (Raxone) Improves Inspiratory Function in Patients With Duchenne Muscular Dystrophy

Encouraging results reported from pivotal phase 3 trial

Data from a pivotal phase 3 study demonstrating the positive effect of idebenone (Raxone, Santhera Pharmaceuticals) on inspiratory function in patients with Duchenne muscular dystrophy (DMD) have been published online in Pediatric Pulmonology.

The assessment of dynamic inspiratory function provides valuable information about the degree and progression of pulmonary involvement in patients with DMD. The pivotal DELOS trial evaluated the effect of idebenone on the maximum inspiratory flow (V'I,max) generated during a forced vital capacity (FVC) maneuver. DMD patients in the study’s two treatment groups––idebenone (n = 31) and placebo (n = 33)––had comparable and abnormally low V'I,max(FVC) at baseline. During the study period, V'I,max(FVC) further declined by –0.29 liters per second (L/s) in patients receiving placebo at week 52 (P = 0.008), whereas it remained stable in patients treated with idebenone (change from baseline to week 52: 0.01 L/s; P = 0.950). The between-group difference demonstrated a positive treatment effect for idebenone by 0.27 L/s (P = 0.043) at week 26 and by 0.30 L/s (P = 0.061) at week 52. In addition, during the study period, the fraction of the maximum flow that is not used during tidal breathing, called the inspiratory flow reserve (IFR), improved by 2.8% in patients treated with idebenone and worsened by –3.0% in patients given placebo at week 52, for a between-group difference of 5.8% (P = 0.040).

DMD is one of the most common and devastating types of muscle degeneration and results in rapidly progressive muscle weakness. The disease is characterized by loss of the protein dystrophin, which leads to cell damage, impaired calcium homeostasis, elevated oxidative stress, and reduced energy production in muscle cells. This results in progressive muscle weakness and wasting and early morbidity and mortality due to respiratory failure.

Idebenone is a synthetic short-chain benzoquinone and a cofactor for the enzyme NAD(P)H:quinone oxidoreductase (NQO1) that can stimulate mitochondrial electron transport, thereby reducing and scavenging reactive oxygen species (ROS) and supplementing cellular energy levels.

Following an exploratory phase 2 trial (DELPHI), the safety and efficacy of idebenone were investigated in the confirmatory phase 3, double-blind, placebo-controlled DELOS trial. DELOS randomly assigned 64 patients, not taking concomitant glucocorticoids, to receive either idebenone (900 mg/day) or matching placebo. The trial met its primary endpoint and demonstrated that idebenone can slow the loss of respiratory function and reduce bronchopulmonary complications.

Source: Santhera Pharmaceuticals; September 13, 2016.