EU clears first drug therapy for rare disease cALD

Neuraxpharm and Minoryx Therapeutics' Nezglyal has become the first approved drug therapy in the EU for rare neurodegenerative disease cerebral adrenoleukodystrophy (cALD), and is set to launch before the end of the year.

The green light from the European Commission is the first for Nezglyal (leriglitazone), an oral PPAR gamma agonist that is indicated for the treatment of male cALD patients, aged two to 12, who have gadolinium-negative brain lesions.

cALD is a devastating and fatal condition with no drug treatments available that leads to progressive destruction of the myelin sheath that surrounds nerve cells, resulting in a relentless deterioration that typically leads to acute neurological decline and death within three to four years.

Neuraxpharm and Minoryx originally developed leriglitazone as a treatment for children and adults with the disease, but suffered a setback in the ADVANCE trial. Their first marketing application was turned down in 2024, but data from the paediatric NEXUS trial – showing the drug was able to slow down progression – set up a second filing last year.

The two companies tried their luck at getting approval for both children and adults at the second attempt, but the EMA's human medicines committee, the CHMP, opted to recommend the drug only for the narrower indication when it delivered a positive opinion on the filing in July.

Despite the narrower indication, Neuraxpharm and Minoryx said the approval is a "significant milestone" for patients, as Nezglyal has become the first approved pharmacological treatment for cALD in the EU.

"With childhood cALD, neurodegeneration is irreversible, so it is critical to halt disease progression early, ideally, before symptoms surface and signs of neuroinflammation appear," commented Dr Caroline Sevin of the Hôpital du Kremlin Bicêtre in France, who was one of the NEXUS investigators.

"Invasive procedures, such as haematopoietic 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 added.

"That we now have a pharmacological treatment for early intervention is a major advance in our treatment of cALD."

Neuraxpharm will commercialise the product in Europe, and said the first launch is expected to be in Germany by the end of the year, with others following reimbursement negotiations.

Meanwhile, the two companies are running a phase 3 trial to build the case for Nezglyal into adult cALD (CALYX) and a phase 2a trial in children with Rett syndrome, another severe genetic neurological and developmental disorder.

The first approved therapy for cALD was Bluebird Therapeutics' gene therapy Skysona (elivaldogene autotemcel), which never launched and had its license withdrawn in 2024 for commercial reasons.