Neuraxpharm and Minoryx Therapeutics have secured European Commission approval for Nezglyal (leriglitazone), making it the first approved drug therapy for rare disease cALD — cerebral adrenoleukodystrophy — in the European Union, with a commercial launch expected before the end of the year.
The regulatory green light marks a significant milestone in the treatment landscape for this devastating and fatal rare neurological condition, which until now had no approved pharmacological options.
What Is cALD and Why This Approval Matters
Cerebral adrenoleukodystrophy is a rare neurodegenerative disease that leads to progressive destruction of the myelin sheath surrounding nerve cells. The condition follows a relentless course of deterioration, typically resulting in acute neurological decline and death within three to four years of onset. There have been no drug treatments available for the disease — until now.
Nezglyal is an oral PPAR gamma agonist indicated for male cALD patients aged two to 12 who have gadolinium-negative brain lesions. Its approval for rare disease cALD represents the first time a pharmacological treatment has been made available to this patient population in the EU.
The Road to Approval
Neuraxpharm and Minoryx originally developed leriglitazone for both children and adults with cerebral adrenoleukodystrophy. Their first marketing application was rejected in 2024 following a setback in the ADVANCE trial.
However, data from the paediatric NEXUS trial demonstrated that the drug was able to slow disease progression, forming the basis of a second regulatory filing. At the second attempt, the two companies sought approval for both children and adults. The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) delivered a positive opinion in July but recommended the drug only for the narrower paediatric indication.
Despite the more limited scope, both companies have described the outcome as a “significant milestone” for patients.
Dr Caroline Sevin of the Hôpital du Kremlin Bicêtre in France, one of the NEXUS trial investigators, highlighted the clinical importance of the approval.
“With childhood cALD, neurodegeneration is irreversible, so it is critical to halt disease progression early, ideally, before symptoms surface and signs of neuroinflammation appear,” she stated.
Dr Sevin also noted the limitations of existing options: “Invasive procedures, such as hematopoietic stem cell transplantation, are available for more progressed patients. However, they are donor-dependent and can only be applied within a very narrow time window.”
She concluded: “That we now have a pharmacological treatment for early intervention is a major advance in our treatment of cALD.”
Launch Plans and Ongoing Trials
Neuraxpharm will lead the commercialisation of Nezglyal across Europe. The first launch is expected in Germany by the end of the year, with rollouts in other markets to follow subject to reimbursement negotiations.
In parallel, Neuraxpharm and Minoryx are conducting a Phase 3 trial — CALYX — to build the evidence base for Nezglyal in adult cALD patients. A Phase 2a trial in children with Rett syndrome, another severe genetic neurological and developmental disorder, is also underway.
The first approved therapy for cALD was Bluebird Therapeutics’ gene therapy Skysona (elivaldogene autotemcel). However, Skysona never launched commercially and had its license withdrawn in 2024 for commercial reasons, leaving patients without any approved treatment option — a gap that Nezglyal’s approval for rare disease cALD now addresses.
