What is Sonlicromanol?
Sonlicromanol, previously known as KH-176, is a novel drug that has been developed by a Dutch pharmaceutical company called Khondrion.
It is derived from vitamin E, which is an antioxidant found in many different foods.
How does it work?
Sonlicromanol removes damaging chemicals that are produced during normal energy production. These oxygen species, known as free radicals, may be found at higher levels within cells when the mitochondria don’t work properly. Sonlicromanol may also work by increasing the activity of different parts of the energy chain.
What is it supposed to do?
Sonlicromanol thought to protect cells from oxidative stress, which occurs when there are high levels of free radicals. Oxidative stress can cause considerable damage to cells and may contribute to some of the symptoms of mitochondrial disease. Sonlicromanol may also increase the amount of energy the mitochondria can produce, which could reduce some of the symptoms of mitochondrial disease.
Is it a cure?
Unfortunately not. Sonlicromanol cannot correct the underlying genetic defect that causes mitochondrial disease.
What types of mitochondrial disease could it treat?
Sonlicromanol is currently under development for treatment of inherited mitochondrial diseases. If successful, it could be used to treat any inherited mitochondrial disease.
Have there been any trials of Sonlicromanol?
The results of a phase 1 clinical trial of Sonlicromanol were published in 2015. They showed that the drug was well tolerated in healthy male volunteers and had a good pharmacokinetic profile (the affect the body has on the drug).
A ‘first-in-patient’ phase 2a clinical trial, known as the KHENERGY study, was completed in 2017. This trial recruited 20 adult patients with a particular genetic error causing mitochondrial disease (the m.3243A>G mutation). The patients were randomly divided into two groups, with one group receiving Sonlicromanol for 4 weeks and the other receiving a placebo. The groups were then swapped so that all patients received the drug at some point during the trial. This was a double-blind study, meaning that neither the researchers nor the participants knew who was receiving the drug or the placebo.
What happened next?
Results from the phase 2a trial were published in January 2019. They showed that the drug was well tolerated at a dose deemed safe from the phase I study and had no adverse side effects. Clinical outcomes included a significant improvement in mood and alertness, whilst some patients also self-reported fewer migraines. These improvements in a number of clinical endpoints supported further development of Sonlicromanol.
What is the latest update on this trial?
Khondrion have opened a phase 2b trial of Sonlicromanol across Europe. The trial, known as the KHENERGYZE study, aims to further assess the efficacy of Sonlicromanol in improving cognitive function in individuals with symptomatic m. 3243A>G mitochondrial disease. The study is open for recruitment at three internationally recognised mitochondrial centres in Newcastle upon Tyne (UK), Munich (Germany) and Nijmegen (Netherlands).
In addition to the KHENERGYZE study, Khondrion are planning to investigate the potential of the drug in children, with a paediatric study expected to start later in 2020.
In November 2014, Sonlicromanol received ‘orphan drug’ status by the FDA in the US. This aims to advance both the evaluation and development of drugs that have the potential to treat rare diseases and should make it easier for Sonlicromanol to gain marketing approval.
Since this time, Sonlicromanol has been granted Orphan Drug Designation (ODD) by the European Commission for the treatment of MELAS syndrome, Leigh syndrome and maternally inherited diabetes and deafness (MIDD).
Is there more information on these trials?
More information can be found using the following link: