In short
Sonlicromanol is an investigational substance being studied for primary mitochondrial disease caused by a specific genetic change called m.3243A>G. It received orphan designation from the European Medicines Agency in July 2025 for inherited mitochondrial oxidative phosphorylation defects. One Phase 3 trial (NCT06451757) is currently authorised, planning to enrol 220 adults to test whether sonlicromanol can reduce fatigue and improve muscle strength.
Key points
- Sonlicromanol is an investigational medicine for primary mitochondrial disease caused by the m.3243A>G genetic change.
- The only registered trial is a Phase 3 study with 220 planned participants.
- The trial is randomised, double-blind, and placebo-controlled.
- Treatment is given as 180 mg capsules by mouth over 52 weeks.
- The main outcomes are fatigue symptoms and leg muscle strength and balance.
- Sonlicromanol has orphan designation in the EU but is not yet authorised as a medicine.
What is sonlicromanol?
Sonlicromanol is an investigational substance being developed for the treatment of primary mitochondrial disease. It is also known by its chemical form as sonlicromanol hydrochloride. The substance has not yet received marketing authorisation anywhere, meaning it cannot be prescribed outside of clinical trials.
In July 2025, the European Medicines Agency (EMA) granted sonlicromanol an orphan designation for the treatment of inherited mitochondrial oxidative phosphorylation defects. Orphan designation is a status given to medicines being developed for rare diseases. It provides the developer with scientific and regulatory support, but it does not mean the medicine is available or authorised for use.
The developer of sonlicromanol is Khondrion BV, a company based in Nijmegen, the Netherlands.
How does sonlicromanol work?
Primary mitochondrial disease is caused by changes in mitochondrial DNA (mtDNA). Mitochondria are the parts of cells that produce energy. When mitochondria do not work properly, organs and tissues may not get the energy they need to function well. The specific genetic change targeted by sonlicromanol is called m.3243A>G, which affects a gene for transfer RNA in mitochondria.
The precise mechanism of action of sonlicromanol is not described in the available sources. The clinical trial is designed to test whether the substance can reduce tiredness, improve leg muscle strength, and improve balance in people with this genetic change.
Which conditions is sonlicromanol studied for?
- Primary mitochondrial disease with the m.3243A>G variant — a condition caused by a change in mitochondrial DNA that leads to symptoms such as tiredness, weak muscles, stomach or bowel problems, hearing loss, stroke-like episodes, diabetes, pain, and difficulty thinking clearly.
- Associated phenotypes including MIDD, MELAS, and multi-system phenotypes — the m.3243A>G change can cause maternally inherited diabetes and deafness (MIDD), mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), and other combinations of symptoms affecting several body systems.
How is sonlicromanol given?
In the Phase 3 trial, sonlicromanol is given as a capsule containing 180 mg of sonlicromanol hydrochloride, taken by mouth. The comparison arm receives a matching placebo capsule containing microcrystalline cellulose. The treatment period lasts 52 weeks.
What do the clinical trials show?
One clinical trial is registered for sonlicromanol: a Phase 3 study called KHENERFIN with the identifier NCT06451757. The trial is authorised and plans to enrol 220 adult participants. The study is randomised, double-blind, and placebo-controlled, meaning participants are assigned by chance to receive either sonlicromanol or a matching placebo, and neither the participants nor the researchers know who receives which.
The trial measures two primary outcomes after 52 weeks of treatment. The first is the change in the NeuroQoL Fatigue Short Form score, a questionnaire that measures physical fatigue symptoms and how they affect daily living and quality of life. The second is the duration of the 5 Times Sit-to-Stand Test, which measures lower limb skeletal muscle strength and dynamic balance control.
Participants must be adults with a genetically confirmed mitochondrial DNA tRNALeu(UUR) m.3243A>G variant. The study also examines how the body absorbs and removes the medicine.
What side effects are known?
The available sources do not report specific side effects of sonlicromanol. The Phase 3 trial is designed to assess both efficacy and safety, and its results will provide information about the side effect profile of the substance.