Idebenone

Uses

Indications that are or were approved in some territories

Nootropic effects and Alzheimer's disease

Idebenone improved learning and memory in experiments with mice. In humans, evaluation of Surrogate endpoints like electroretinography, auditory evoked potentials and visual analogue scales also suggested positive nootropic effects, but larger studies with hard endpoints are missing.

Research on idebenone as a potential therapy of Alzheimer's disease have been inconsistent, but there may be a trend for a slight benefit. In May 1998, the approval for this indication was cancelled in Japan due to the lack of proven effects. In some European countries, the drug is available for the treatment of individual patients in special cases.

Friedreich's ataxia (Sovrima)

Preliminary testing has been done in humans and found idebenone to be a safe treatment for Friedreich's ataxia (FA), exhibiting a positive effect on cardiac hypertrophy and neurological function. The latter was only significantly improved in young patients. In a different experiment, a one-year test on eight patients, idebenone reduced the rate of deterioration of cardiac function, but without halting the progression of ataxia.

The drug was approved for Friedreich's ataxia in Canada in 2008 under conditions including proof of efficacy in further clinical trials. However, in February 2013, Health Canada announced that idebenone would be voluntarily recalled as of April 2013 by its Canadian manufacturer, Santhera Pharmaceuticals, due to the failure of the drug to show efficacy in the further clinical trials that were conducted. In 2008, the European Medicines Agency (EMA) refused a marketing authorisation for this indication. As of 2013 the drug was not approved for FA in Europe nor in the US, where, as of February 2023, there is only one approved treatment.

Leber's hereditary optic neuropathy (Raxone)

Leber's hereditary optic neuropathy (LHON) is a mitochondrially inherited (mother to all offspring) degeneration of retinal ganglion cells (RGCs) and their axons that leads to an acute or subacute loss of central vision; this affects predominantly young adult males. Santhera completed a Phase III clinical trial in this indication in Europe with positive results, and submitted an application to market the drug to European regulators in July 2011. It is approved by EMA for this indication and was designated an orphan drug in 2007.

Indications being explored

Duchenne muscular dystrophy (Catena)

After experiments in mice and preliminary studies in humans, idebenone has entered Phase II clinical trials in 2005 and Phase III trials in 2009.

Other neuromuscular diseases

Phase I and II clinical trial for the treatment of MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) was conducted. Phase I/II trial for primary progressive multiple sclerosis concluded that Idebenone did not inhibit disability progression.

As of 2022, a phase III clinical trial is ongoing for the treatment of Parkinson's disease.

Life style

Idebenone is claimed to have properties similar to CoQ10 in its antioxidant properties, and has therefore been used in anti-aging on the basis of free-radical theory. Clinical evidence for this use is missing. It has been used in topical applications to treat wrinkles.

Pharmacology

In cellular and tissue models, idebenone acts as a transporter in the electron transport chain of mitochondria and thus increases the production of adenosine triphosphate (ATP) which is the main energy source for cells, and also inhibits lipoperoxide formation. Positive effects on the energy household of mitochondria has also been observed in animal models. Clinical relevance of these findings has not been established.

Pharmacokinetics

Idebenone is well absorbed from the gut but undergoes excessive first pass metabolism in the liver, so that less than 1% reach the circulation. This rate can be improved with special formulations (suspensions) of idebenone and by administering it together with fat food; but even taking these measures bioavailability still seems to be considerably less than 14% in humans. More than 99% of the circulating drug are bound to plasma proteins. Idebenone metabolites include glucuronides and sulfates, which are mainly (~80%) excreted via the urine.

References

References

1. (15 February 2007). "Raxone EPAR".
2. (20 November 2008). "CHMP Assessment Report for Sovrima". [[European Medicines Agency]].
3. {{ClinicalTrialsGov. NCT00229632. Idebenone to Treat Friedreich's Ataxia
4. {{ClinicalTrialsGov. NCT00654784. Efficacy and Tolerability of Idebenone in Boys With Cardiac Dysfunction Associated With Duchenne Muscular Dystrophy (DELPHI)
5. (17 September 2018). "Raxone".
6. (November 1999). "Effects of ligustrazine, tanshinone II A, ubiquinone, and idebenone on mouse water maze performance". Zhongguo Yao Li Xue Bao = Acta Pharmacologica Sinica.
7. (July 1998). "Dose-effect relationship of idebenone in an experimental cerebral deficit model. Pilot study in healthy young volunteers with piracetam as reference drug". Arzneimittel-Forschung.
8. (January 2002). "Safety and efficacy of idebenone versus tacrine in patients with Alzheimer's disease: results of a randomized, double-blind, parallel-group multicenter study". Pharmacopsychiatry.
9. (May 1997). "Cognitive enhancement therapy for Alzheimer's disease. The way forward". Drugs.
10. (October 2007). "Neurological effects of high-dose idebenone in patients with Friedreich's ataxia: a randomised, placebo-controlled trial". The Lancet. Neurology.
11. (September 2008). "Idebenone in Friedreich's ataxia". Expert Opinion on Pharmacotherapy.
12. (May 2003). "Idebenone treatment in Friedreich's ataxia: neurological, cardiac, and biochemical monitoring". Neurology.
13. "Heath Canada Fact Sheet - Catena".
14. [http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2013/23509a-eng.php Voluntary Withdrawal of Catena from the Canadian Market]
15. Margaret Wahl for Quest Magazine, 28 May 2010. [http://quest.mda.org/news/fa-research-idebenone-strikes-out-again FA Research: Idebenone Strikes Out Again] {{Webarchive. link. (27 September 2017)
16. [https://web.archive.org/web/20230301015303/https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-treatment-friedreichs-ataxia#:~:text=FDA%20has%20approved%20Skyclarys%20(omaveloxolone,recommended%20dosage%20of%20150%20mg. FDA approves first treatment for Friedreich's ataxia]
17. (September 2011). "A randomized placebo-controlled trial of idebenone in Leber's hereditary optic neuropathy". Brain.
18. Staff. (26 July 2011). "Santhera publishes pivotal trial results of idebenone and goes for EU approval".
19. (January 2009). "Long-term blinded placebo-controlled study of SNT-MC17/idebenone in the dystrophin deficient mdx mouse: cardiac protection and improved exercise performance". European Heart Journal.
20. {{ClinicalTrialsGov. NCT01027884. Phase III Study of Idebenone in Duchenne Muscular Dystrophy (DMD) (DELOS)
21. {{ClinicalTrialsGov. NCT00887562. Study of Idebenone in the Treatment of Mitochondrial Encephalopathy Lactic Acidosis & Stroke-like Episodes (MELAS)
22. {{ClinicalTrialsGov. NCT00950248. Double Blind Placebo-Controlled Phase I/II Clinical Trial of Idebenone in Patients With Primary Progressive Multiple Sclerosis (IPPoMS)
23. (October 2020). "Idebenone does not inhibit disability progression in primary progressive MS". Multiple Sclerosis and Related Disorders.
24. (2022). "Parkinson's Disease Drug Therapies in the Clinical Trial Pipeline: 2022 Update". Journal of Parkinson's Disease.
25. (September 2005). "Clinical efficacy assessment in photodamaged skin of 0.5% and 1.0% idebenone". Journal of Cosmetic Dermatology.
26. (May 1988). "[Effect of idebenone and various nootropic drugs on lipid peroxidation in rat brain homogenate in the presence of succinate]". Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica.