Positive results have been published from a phase IIb clinical trial evaluating the drug candidate sonlicromanol in mitochondrial diseases caused by the m.3243A>G mutation. The trial was conducted in two stages:
- A first, randomised, controlled part in which 27 patients were divided into three groups, depending on whether they received 50 mg, 100 mg sonlicromanol or a placebo twice a day for 28 days.
- An extension phase, which included 15 of these patients. All received 100 mg of sonlicromanol twice a day for one year.
The results of the first part showed that :
- The primary endpoint of the Cogstate IDN score (a measure of attention) was not achieved.
- Nevertheless, after adjusting for the severity of this criterion at inclusion, a significant improvement compared with placebo was observed in the most severely affected patients.
- The secondary results were analysed using this adjusted model. The results showed an improvement in the HADS-D depression scale, the BDI (Beck Depression Inventory) score and the CFQ (25-item Cognitive Failure Questionnaire) score.
In the extension phase:
- Greater positive changes were seen with long-term treatment.
- Significant improvements were observed particularly in the TAP (Test of Attentional Performance), the BDI, the EQ-5D-5L VAS quality of life scale and pain assessed by the RAND SF-36 score.
- Most patients improved on the Five Times Sit-to-Stand Test.
Although the primary endpoint was not met, several positive results justify the setting up of a phase III trial in patients with diseases due to the m.3243A>G mutation, who are more homogeneous and more severely affected, for 52 weeks, to determine more precisely the potential of this drug candidate, which is also well tolerated.
