Leriglitazone (Nezglyal) has received a positive opinion from the European Medicines Agency's Committee for Medicinal Products for Human Use, positioning it to become the first approved pharmacological treatment for cerebral adrenoleukodystrophy in the EU — a disease that currently leaves affected boys with no drug-based options and a mean survival of three to four years from onset of progression. The CHMP adopted its opinion on July 23, 2026, recommending marketing authorization under exceptional circumstances for Spain-based Minoryx Therapeutics, with European Commission approval expected by the end of September 2026.
The indication is tightly defined: male patients with adrenoleukodystrophy (ALD) aged 2 to 12 years who have non-Gadolinium enhancing lesions on brain MRI — reflecting earlier-stage disease — and a Neurological Functional Score of 0 or 1. The restriction to Gd-negative lesions is clinically significant. In cALD, lesions transition from Gd-negative to Gd-positive as the blood-brain barrier is damaged and disease accelerates; intervening at the Gd-negative stage represents the window in which stabilization is most plausible.
The "exceptional circumstances" designation reflects the rare pediatric setting: the EMA grants this pathway when comprehensive data cannot be assembled at the time of authorization, typically because the condition is too rare to conduct standard-sized trials.
Leriglitazone is an orally bioavailable, brain-penetrant, selective PPARγ agonist. By modulating peroxisome proliferator-activated receptor gamma, it engages pathways involved in neuroinflammation, demyelination, mitochondrial dysfunction, oxidative stress, and axonal degeneration — several of the overlapping mechanisms that drive cALD progression. The oral route and CNS penetration are relevant differentiators given that the condition requires long-term management in young children.
The CHMP opinion was based primarily on results from the Phase II/III NEXUS trial, an open-label study in male paediatric patients with early-stage cALD. The key finding was that patients remained clinically and radiologically stable after more than 96 weeks of treatment, or at the visit preceding haematopoietic stem cell transplantation (HSCT). In a disease defined by rapid neurological deterioration — loss of voluntary movement, inability to swallow, cortical blindness, and death within a few years of progression — sustained stability over nearly two years represents a clinically meaningful outcome. Supportive evidence came from the ADVANCE trial in adult male cALD patients, which indicated leriglitazone reduced disease progression, and from compassionate use programme data. More than 170 patients with cALD have received the drug across clinical and compassionate use settings.
The absence of any approved pharmacological treatment for cALD in the EU defines the competitive context entirely. The only existing intervention for childhood cALD is HSCT, including gene therapy-based HSCT, which is invasive, requires myeloablative chemotherapy with associated comorbidities, is not universally accessible, and carries meaningful procedural risk. In adults, HSCT experience is limited and often not recommended, particularly in patients with advanced adrenomyeloneuropathy. Leriglitazone would not replace HSCT — the NEXUS data include patients who proceeded to transplantation — but would represent the first option for disease stabilization that does not require the patient to undergo a transplant procedure.