Leriglitazone Treatment May Slow Progression of Adrenomyeloneuropathy 

A clinical trial (NCT03231878) of leriglitazone (MIN-102; Minoryx Therapeutics, Barcelona, Spain) for adrenomyeloneuropathy showed improvements in the clinical measure of body sway and blood and neuroimaging biomarkers. Although treatment did not result in the prespecified outcome of 45-meter improvement on the 6-minute walk test, these other improvements suggest that leriglitazone may slow disease progression. 

With eyes closed and feet apart, those treated with leriglitazone had mean change of -1.013 vs an increase of 1.380 with placebo in anteroposterior body sway but no significant change in mediolateral or total body sway. With eyes closed and feet together, those treated with leriglitazone had mean change of -1.341 on total body sway and -3.325 mediolateral sway vs 0.121 and 0.724 increases, respectively, with placebo. Changes in anteroposterior sway with eyes closed and feet together did not differ significantly between groups. 

Notably, no participant treated with leriglitzone (n=77) had new inflammatory lesions or growth of noninflammatory lesions compared with 15.4% of those who received placebo. 

Participants were 116 adult men with baseline scores less than 6 on the Expanded Disability Status Scale (EDSS) who could walk for 6 minutes and stand on a force plate for 20 seconds. Participants were randomly assigned 2:1 to receive leriglitazone or placebo for 96 weeks, followed by an open-label extension.

The rate of discontinuation for adverse events was 10.4% for leriglitazone vs 5.1% for placebo. Adverse events that were higher in those treated with leriglitazone included edema, weight gain, increased lacrimation, and cardiac events in 5 individuals. Cardiac adverse events were angina, aortic valve stenosis, 1st degree atrioventricular block, left bundle branch block, coronary artery occlusion, extra systoles, palpitations, pericardial effusion, and tachycardia. 

Leriglitazone is a novel brain-penetrant and selective peroxisome proliferator-activated receptor gamma (PPARγ) agonist thought to protect neurons and astrocytes and the integrity of the blood-brain barrier by preventing monocyte and microglial activation.

Uwe Meya, CMO, Minoryx said, “On behalf of the ADVANCE global investigator group we submitted this presentation to present these results at AAN’s Annual Meeting as a conference for a leading neurological scientific society with delegates from the US as well as across the globe. This enables the international neurological community to discuss Minoryx’s approach for a variety of orphan diseases with no available therapeutic options and leriglitazone’s significant clinical benefits in patients suffering from AMN.”

Leriglitazone has been granted orphan drug status for X-linked adrenoleukodystrophy from the FDA and the EMA and fast track and rare pediatric disease designation from the FDA for the treatment of X-ALD. A phase 3 trial (NCT04528706) is enrolling boys with X-ALD for treatment with leriglitazone prior to undergoing hematopoietic stem cell transplant.

These data were presented at the American Academy of Neurology Virtual Annual Meeting April 17-22, 2021.