EXECUTIVE SUMMARY

Comitè d'Avaluació de Medicaments d'Utilització Hospitalària (CAMUH). Idebenone for the treatment of Friedreich's ataxia; 2012.
[Full text available in Catalan, PDF 644 KB]

Background
Friedreich's ataxia (FA) is a degenerative disease with an autosomal recessive inheritance pattern that has been related to the accumulation of iron within the mitochondria and the formation of free radicals. The most common clinical manifestations are neurological alterations, cardiomyopathy and diabetes mellitus. Virtually all patients present with ataxia in the four limbs and gait alterations after the age of 5, although in some cases these alterations cases may occur earlier. The main cardiac manifestation is arrhythmia and complications caused by cardiomyopathy, which are a frequent cause of death, often around the age of 30-40 years. There is no specific treatment to correct the defect causing AF.

Idebenone (Sovrima®) is a benzoquinone with a structure similar to the coenzyme Q10. It is a powerful antioxidant that binds to oxygen of free radicals and enhances the flow of electrons in the electron transfer chain. Idebedone was designated as an orphan drug by the European Medicines Agency (EMA) in 2004 and received a negative opinion for commercialization in 2008 by the Committee for Medicinal Products for Human Use (CHMP) of the EMA mainly due to the lack of evidence regarding its efficacy in AF. This decision was ratified a few months later.

Objectives
To analyze the scientific evidence available on the efficacy and safety of idebenone compared with any alternative treatment, including placebo, in patients with AF.

Methodology
Systematic review of scientific evidence available until July 2011. The internal validity and grade of recommendation of the included clinical trials were assessed by a reviewer using Scottish Intercollegiate Guidelines Network (SIGN) criteria. A qualitative synthesis of the scientific evidence was carried out.

Results
The main data on the efficacy and safety of idebenone in patients with AF come from 11 clinical trials (4 comparative trials and 7 non-comparative trials).

The results described regarding the main efficacy variables (variables of cardiac and neurological function) are discordant among clinical trials. Regarding safety, treatment with idebenone is generally safe and well-tolerated. The most common adverse effects are gastrointestinal disturbances. Isolated cases of neutropenia, transaminitis and tachycardia have been reported.

Conclusions
The evidence available in the literature confirms the safety of idebenone, but cannot prove its efficacy in the treatment of AF. Therefore, its use would only be recommended within the context of a clinical trial.