Idebenone (Raxone®/Catena®)
Raxone/Catena (idebenone) is a synthetic short-chain benzoquinone and a substrate for the enzyme NAD(P)H:quinone oxidoreductase (NQO1) capable of stimulating mitochondrial electron transport and supplementing cellular energy levels. It is structural analogue of CoQ10 with enhanced bioavailability.
INACTIVE: Stages of Development for Idebenone
The drug development process can be thought of as a series of stages, and drugs must successfully pass through each stage to become available to patients. This treatment has been evaluated, and the program has been discontinued. Thus, it is not in the pipeline.
A phase II tolerability and efficacy trial with low, intermediate, and high doses of idebenone was conducted. This was a 6 month phase 2 double-blind, placebo-controlled trial to assess the safety and efficacy of idebenone administered to adolescents and children with FA. Study population included children (ages 9-11) and adolescents (ages 12-17) with FA divided evenly among 4 treatment arms (placebo, low, intermediate, and high dose idebenone). The results suggested that treatment with intermediate- and high-dose idebenone had beneficial effects on neurological symptoms.
IONIA: Study to Assess the Efficacy, Safety and Tolerability of Idebenone in the Treatment of Friedreich’s Ataxia (IONIA). This study was a phase III Double-Blind, Randomized, Placebo-Controlled Study of the Efficacy, Safety and Tolerability of Idebenone in the Treatment of Friedreich’s Ataxia Patients ages 8-17 years. The study evaluated two doses of idebenone compared to placebo over 6 months then subjects were enrolled into a 12-month open label extension study (IONIA-E).
The study did demonstrate that the drug was safe and well-tolerated and that the individuals who received Idebenone improved their neurological rating scores more than those on placebo. However, the benefit did not reach statistical significance. IONIA and IONIA-E Results were published in Meier et al, J Neurol, 2011.
A sub-study evaluated cardiac changes via echocardiogram during the 6-month IONIA study. Left ventricular mass index, posterior wall thickness, EF, and ECG parameters were not significantly improved by treatment with idebenone. Therefore, this study did not provide evidence of benefit in this cohort over a 6-month treatment period.
MICONOS: A Phase III Double-blind, Randomised, Placebo-controlled Study of the Efficacy, Safety and Tolerability of Idebenone in the Treatment of Friedreich’s Ataxia Patients. The purpose of this trial was to study the efficacy (neurologic and cardiac), safety and tolerability of idebenone in 12 months of treatment in children and adults with Friedreich’s Ataxia. Three doses of idebenone were evaluated and compared to placebo. The study enrolled >230 participants. The study did not reach primary or secondary endpoints which were neurological rating scales (ICARS and FARS).
Full results are available here.
July 2008: Catena® (idebenone) received conditional market approval in Canada for the treatment of Friedreich’s ataxia (FA).
April 2013: However, based on additional data that fails to confirm that treatment with Catena® is beneficial in FA, Santhera Pharmaceuticals announced it will discontinue sales of the drug on April 30, 2013. The company reported that no specific safety issues were identified in connection with removal of Catena® from the market.
The drug was not approved for use in the United States.
Idebenone is approved in Europe for the treatment of Leber’s hereditary optic neuropathy (LHON), a rare mitochondrial disorder.