CHMP Recommends Minoryx's NEZGLYAL as First Pharmacological Treatment for Pediatric Cerebral Adrenoleukodystrophy
核心洞察
The EMA's CHMP has recommended marketing authorization under exceptional circumstances for NEZGLYAL (leriglitazone) in boys aged 2–12 with early-stage, non-gadolinium-enhancing cALD brain lesions.
The positive opinion follows a previous 2024 rejection and is supported by the Phase 2/3 NEXUS study, where 35% of evaluable patients showed arrested disease over 96 weeks.
Six of nine boys with non-gadolinium-enhancing lesions stabilized, compared to only one of eleven with gadolinium-enhancing lesions, leading to a narrowly defined indication.
The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization under exceptional circumstances for NEZGLYAL (leriglitazone), an oral, brain-penetrant PPAR gamma (搜索) agonist developed by Minoryx Therapeutics (搜索). The recommendation, adopted on July 23, 2026, positions the drug to become the first approved pharmacological treatment for cerebral adrenoleukodystrophy (搜索) (cALD) in the European Union, though only for a narrowly defined subset of young male patients.
The recommended indication covers males with adrenoleukodystrophy (ALD) aged 2 to 12 years with non-gadolinium-enhancing lesions on brain MRI and a Neurological Functional Score (NFS) of 0 or 1. European Commission final authorization is expected by the end of September 2026.
A Comeback After Prior Rejection
The positive CHMP opinion marks a significant turnaround for Minoryx, which saw its first marketing application for leriglitazone rejected by the EMA in May 2024 following a re-examination. Regulators at that time concluded that the evidence submitted did not establish the drug's benefits in cALD, after the main Phase 2/3 ADVANCE trial missed its primary endpoint.
Minoryx subsequently filed a new application supported by the NEXUS study, a 96-week, open-label Phase 2/3 trial conducted in children with cALD, along with additional real-world evidence from compassionate use programs.
NEXUS Data and the Lesion-Stage Divide
Results from the NEXUS study revealed a stark difference in treatment response based on lesion stage. Among 20 evaluable boys, seven (35%) had clinically and radiologically arrested disease after treatment for up to 96 weeks or until undergoing hematopoietic stem cell transplantation (HSCT).
The response stratified sharply: six of nine boys with non-gadolinium-enhancing lesions achieved stabilization, while only one of eleven boys with gadolinium-enhancing lesions stabilized. This differential response directly shaped the final recommended indication, which excludes patients with gadolinium-enhancing lesions—considerably narrower than the pediatric and adult population originally targeted in the application.
Disease Background and Unmet Need
X-linked adrenoleukodystrophy (搜索) (X-ALD) is an orphan neurodegenerative disease with a global incidence of approximately 6–8 per 100,000 live births. Progressive cALD occurs in 31–35% of ALD patients in childhood, with typical onset between ages 2 and 12. The condition is characterized by demyelinating brain lesions that can become rapidly progressive, leading to acute neurological decline and death, with a mean survival of three to four years.
Currently, no pharmacological treatment is available for cALD in the EU. While HSCT can arrest the disease in childhood, it is an invasive procedure available only to a portion of patients. Gene therapy-based HSCT requires myeloablative chemotherapy with associated comorbidities and is not globally accessible.
Mechanism of Action and Development Program
Leriglitazone is an orally bioavailable, brain-penetrant, selective PPAR gamma (搜索) agonist. It has demonstrated preclinical proof-of-concept in animal models by modulating pathways linked to neuroinflammation, demyelination, mitochondrial dysfunction, oxidative stress, and axonal degeneration. More than 170 patients with cALD have received treatment to date.
The drug has been granted orphan drug status for X-ALD by both the FDA and EMA, as well as Fast Track and Rare Pediatric Disease designations from the FDA.
Commercialization and Ongoing Trials
Minoryx and Neuraxpharm Group (搜索) entered into a license agreement under which Neuraxpharm will commercialize NEZGLYAL in Europe following marketing authorization. Neuraxpharm, a leading European specialty pharmaceutical company focused on CNS disorders, has a direct presence in more than 20 European countries.
"The positive CHMP opinion is a regulatory validation, and we are very pleased that we will soon be able to provide a new therapeutic option to boys suffering from cALD," said Marc Martinell, CEO of Minoryx. "The journey continues towards US approval and future European label-expansion, as we generate new data in adult male cALD patients with gadolinium-enhancing lesions from the ongoing CALYX trial."
Dr. Jörg Thomas Dierks, CEO of Neuraxpharm, added: "cALD is a severe neurodegenerative disease and we look forward to bringing NEZGLYAL, a long-awaited treatment, to European patients following EC approval later this year."
The development program continues with the placebo-controlled Phase 3 CALYX trial in adult men with progressive cALD, with read-out expected by early 2028, and the TREE Phase 2a trial in pediatric patients with Rett syndrome (搜索), with results anticipated by the end of 2026.