Duchenne Muscular Dystrophy
Duchenne Muscular Dystrophy is the most common and a devastating type of muscular degeneration . It is a genetic disease that is inherited in an X-linked mode. Duchenne Muscular Dystrophy is characterized by a loss of the protein dystrophin, leading to progressive muscle weakness and wasting through a complex cascade that involves impaired calcium homeostasis, mitochondrial dysfunction and oxidative stress. The average age of onset is between 3 and 5 years with a loss of ambulation in teenage patients. Dilated cardiomyopathy and respiratory failure are commonly associated with this chronic disease leading to early morbidity and mortality in Duchenne patients.
There is currently no approved treatment for Duchenne Muscular Dystrophy.
Clinical development of CatenaŽ (idebenone) in Duchenne Muscular Dystrophy
Following studies in a disease relevant animal model (Click here Buyse et al: Long-term blinded placebo-controlled study of SNT-MC17/idebenone in the dystrophin deficient mdx mouse: cardiac protection and improved exercise performance. Eur Heart J. 2009; 30(1):116-24), a Phase IIa double-blind, randomized placebo-controlled clinical trial (DELPHI) was conducted to investigate the tolerability and efficacy of idebenone therapy in children with Duchenne Muscular Dystrophy. Twenty-one Duchenne patients (aged 816 years) were randomly assigned to daily treatment with 450 mg idebenone (CatenaŽ) (n=13) or placebo (n=8) for 12 months. For the DELPHI study results, click here Buyse et al: Idebenone as a novel, therapeutic approach for Duchenne muscular dystrophy: results from a 12 month, double-blind, randomized placebo-controlled trial. Neuromuscul Disord. 2011; 21(6):396-405 or here Buyse et al: Effects of Glucocorticoids and Idebenone on Respiratory Function in Patients With Duchenne Muscular Dystrophy. Pediatric Pulmonology 2012; DOI 10.1002/ppul.22688.
The ongoing pivotal Phase III DELOS study (DuchEnne Muscular Dystrophy Long-term IdebenOne Study) is a double-blind, randomized, placebo-controlled clinical trial evaluating the safety, tolerability and efficacy of 900 mg/day idebenone (CatenaŽ) compared to placebo. Study centers in Europe and US have recruited patients aged 10 to 18 years for this 12-month clinical trial. The primary endpoint of the DELOS study is the change from baseline to week 52 in respiratory function measured by peak expiratory flow (PEF). Secondary endpoints relate to other respiratory parameters, muscle strength and motor function, as well as quality of life.
Recently, the DELOS study successfully passed a planned interim futility and safety analysis.