The European Commission has granted marketing authorization under exceptional circumstances for NEZGLYAL® (leriglitazone), the first pharmacological treatment approved for cerebral adrenoleukodystrophy (cALD) in the European Union. The therapy targets male patients aged 2 to 12 years with gadolinium-negative brain lesions. Neuraxpharm Group and Minoryx Therapeutics announced the approval, which is valid across all 27 EU member states, Norway, Iceland, and Liechtenstein.
New oral option for early intervention
NEZGLYAL® is an orally bioavailable, brain-penetrating, selective PPAR gamma agonist. The medication is taken daily and offers a non-invasive, disease-modifying option for children with Gd-negative cALD. The approval is based on results from the Phase 2/3 NEXUS1 study and additional real-world evidence from compassionate use programs.
The European launch is expected to begin in Germany by the end of the year. Additional launches in other countries will depend on the completion of national reimbursement negotiations. Neuraxpharm is also evaluating access pathways for eligible patients.
Early intervention is critical because neurodegeneration in childhood cALD is irreversible. Until now, there were no pharmacological treatment options for this stage of the disease. Invasive procedures, such as hematopoietic stem cell transplantation, are available for more progressed patients. However, these treatments are donor-dependent and can only be applied within a very narrow time window. Dr. Caroline Sevin, MD, PhD, of CRMR LeukoFrance, Hôpital du Kremlin Bicêtre, France, noted that having a pharmacological treatment for early intervention is a major advance in the treatment of cALD.
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Impact on a rapidly progressing disease
Cerebral adrenoleukodystrophy is a rapidly progressing neurodegenerative disease that severely impacts the lives of patients and their families. It is characterized by demyelinating brain lesions that can lead to acute neurological decline and death within three to four years. The condition predominantly affects the brain and is an aggressive form of X-linked adrenoleukodystrophy (X-ALD), which has an incidence of approximately 6 to 8 per 100,000 live births.
Minoryx and Neuraxpharm entered into a license agreement under which Neuraxpharm will commercialize the product in Europe following the marketing authorization. Dr. Jörg Thomas Dierks, CEO of Neuraxpharm Group, stated that the approval reinforces the company’s commitment to advancing innovative medicines that target central nervous system diseases with significant unmet clinical need.
Development efforts continue as the companies generate more data towards expanding the label within X-ALD and other orphan indications. Enrolment has now been completed in the CALYX2 Phase 3 trial in adult male cALD patients with Gd-enhancing lesions. Read-outs are expected in early 2028. The ongoing TREE3 Phase 2a trial in paediatric patients with Rett syndrome is expected to provide results by the end of 2026.