What is Idebenone?
Idebenone, also known as Raxone, is a drug that has been developed by a Swiss pharmaceutical company called Santhera Pharmaceuticals. It is the first and only approved treatment for patients with a particular form of Mitochondrial Disease, known as Leber’s hereditary optic neuropathy (LHON). LHON is caused by genetic mistakes (mutations) in mitochondrial DNA and symptoms are mostly limited to the nerve cells at the back of the eye. LHON is characterised by a rapid loss of sight in both eyes.
Idebenone is a synthetic compound similar to the naturally occurring CoEnzyme Q10, which is essential for proper energy production within the mitochondria. Idebenone has the advantage of being more water-soluble than CoEnzyme Q10 and may cross into the brain more easily.
How does it work?
Idebenone helps to move electrons along the energy chain when a part of the chain is faulty. This can improve energy production in cells that are still alive but can’t make enough energy to work properly. Idebenone works by bypassing the part of the energy chain with the problem.
Idebenone is also an antioxidant that can protect cells against damaging chemicals produced during energy production. These oxygen species, known as free radicals, may be found at higher levels within cells when the energy chain isn’t working properly.
What is it supposed to do?
Idebenone is thought to restore the cell’s ability to produce energy when there is a problem with the energy chain. This means that cells which are inactive but still alive may start working again, which can lead to improved vision in some patients with LHON.
Is it a cure?
Idebenone cannot correct the underlying genetic defect that causes LHON. However, it can help prevent or reverse vision loss even if blindness has occurred. It is important that patients are diagnosed and treated early to give them the best chance of the medication working.
What types of Mitochondrial Disease could it treat?
Idebenone is approved as a treatment for patients with LHON. The potential use of Idebenone to treat another mitochondrial disease, known as MELAS, has been investigated but there is currently little information available on the outcome of a clinical trial that was completed in 2012.
Have there been any trials?
A phase 2 clinical trial, known as RHODOS, was completed in 2010 which assessed the safety and efficacy of Idebenone for LHON. The trial recruited 85 patients from medical centres in the UK, Canada and Germany. All participants had one of the three main mtDNA mutations causing LHON and a disease onset of less than 5 years. The patients were randomly divided into two groups, with one group receiving Idebenone for a period of 24 weeks and the other receiving a placebo (dummy treatment). This was a double-blind study, meaning that neither the researchers nor the participants knew who was receiving the drug or the placebo.
The main outcome measure was improved vision, based mostly on the number of letters patients could read on a standard eye test chart. By the end of the study, patients treated with Idebenone were able to read more letters on the chart compared with patients receiving the placebo. Furthermore, some patients who were unable to read any letters on the chart at the beginning of the study were able to read at least one line during the eye test after treatment.
What happened next?
Idebenone was approved in the EU as a treatment for LHON under ‘exceptional circumstances’, meaning that its clinical benefit continues to be evaluated. The decision was based on the lack of available treatments for vision loss in LHON patients. It was also decided that the benefits of the drug were greater than the risks, with only mild to moderate side-effects reported (including nasopharyngitis (inflammation of the nose and throat), mild to moderate diarrhoea and back pain).
Further studies - ongoing
Santhera are currently conducting additional studies on the long-term effects and safety of Idebenone for patients with LHON. This includes a phase 4 trial, known as LEROS, which began in May 2016. The study aims to recruit 250 LHON patients treated with Idebenone over the next 4 years. There are a number of centres in the USA and Europe taking part, including 4 centres in the UK that are actively recruiting patients (Cardiff, London, Manchester and Romford). Further information can be found using the following link: https://clinicaltrials.gov/ct2/show/study/NCT02774005?term=raxone&rank=2&show_locs=Y#locn
A recent update on the outcome of the RHODOS study reported that around 30% of LHON patients treated with Idebenone achieved a clinically relevant recovery in their vision compared to only 10% in the placebo group (as it appears that in a small % of LHON patients, their vision self recovers). This improvement appeared to be irrespective of their initial ability to read a standard eye chart, or the duration of the disease.
Is there more information?
More information can be found using the following links: