Leriglitazone halts cerebral adrenoleukodystrophy course

Key takeaways:

• Treatment with leriglitazone showed disease arrest in seven of 20 patients.
• The treatment was generally well-tolerated, with adverse events being mild to moderate.

SAN DIEGO —Leriglitazone appeared to stop disease progress both clinically and via imaging in a small cohort of boys with cerebral adrenoleukodystrophy, or cALD, at 96 weeks, according to a presenter.

“Cerebral adrenoleukodystrophy … occurs rapidly in childhood and more than 90% of these boys … will go on to progress to neurological devastation and death within a few years,” Patricia L. Musolino, MD, PhD, a critical care, pediatric and vascular neurologist at Massachusetts General Hospital, said during a late-breaking session at the American Academy of Neurology Annual Meeting.

Musolino and colleagues reported on the safety and efficacy of leriglitazone, an oral, brain-penetrant peroxisome proliferator-activated receptor agonist, in boys with the rare condition prior to hematopoietic stem cell transplantation.

They conducted the NEXUS clinical trial at three sites across Europe between February 2020 and April 2025. Their analysis included 20 boys (mean baseline age, 7.7 years), with a confirmed cALD diagnosis, major functional disability (MFD) score of 0 and a Loes score between one and 10. The patients had not undergone hemopoietic stem cell transplantation (HSCT).

Participants were split between those with nonenhancing lesions and those with gadolinium-enhancing lesions at baseline, then given a once-daily oral suspension of leriglitazone, with an adjusted target plasma concentration of 170 micrograms-h per milliliter.

The researchers conducted an interim data analysis at 24 weeks and a primary analysis at 96 weeks. The study’s primary endpoint was the proportion of enrollees demonstrating clinically and radiologically defined disease arrest at either week 96 or a visit prior to HSCT.

Disease arrest was defined as a change of five or more on the Neurologic Function Scale, MFD freedom as well as halting of lesion progression shown on MRI. Secondary endpoints included change from baseline in NFS and Loes scores, as well as overall patient survival.

Overall, seven out of 20 patients in the efficacy analysis demonstrated evidence of disease arrest at 96 weeks or during a visit prior to a stem cell procedure. This, the researchers noted, was significantly higher based on an expected 10% arrest rate shown within a natural history cohort.

Data additionally showed that 14 of 20 patients showed no significant lesion growth by the same time points, while MRI analysis determined treatment stabilized lesion growth in both patient subgroups.

A safety analysis was conducted in all participants who received at least one dose of leriglitazone. Musolino and colleagues reported that leriglitazone was generally well-tolerated. Although 22 of 23 patients experienced an adverse event, most were mild to moderate. Eight others recorded serious adverse events, though none were determined to be treatment-related and none led to study withdrawal.

“We conclude that leriglitazone can become an available [therapy], before a transplant or anything, that can slow down this relentless, terrible disease,” Musolino said.