rescue — Photo by Egor Myznik on Unsplash

Approval

CHMP backs Minoryx’s rare disease drug two years after rejection

Spanish biotech Minoryx Therapeutics has secured a positive European regulatory opinion for Nezglyal, two years after regulators rejected an earlier application for the rare neurodegenerative disease drug.

Why it matters: The comeback gives Minoryx a potential route to the first pharmacological treatment for cerebral adrenoleukodystrophy (cALD), but only in a narrowly defined group of young patients.

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) recommended approval under exceptional circumstances for boys aged 2 to 12 with early-stage, non-gadolinium-enhancing brain lesions and little or no neurological impairment.

The backstory: In May 2024, the EMA confirmed its refusal of Minoryx’s first Nezglyal application after a re-examination. Regulators rejected the application after the main Phase 2/3 ADVANCE trial missed its primary endpoint, concluding that the evidence submitted did not establish leriglitazone’s benefits in cALD.

Minoryx subsequently filed a new application supported by the NEXUS study, a 96-week, open-label trial conducted in children with cALD.

By the numbers: Seven of the 20 evaluable boys, or 35%, had clinically and radiologically arrested disease after treatment for up to 96 weeks or until they underwent a stem cell transplant.

The response differed sharply according to the stage of the brain lesions:

Six of nine boys with non-gadolinium-enhancing lesions stabilized.
One of 11 boys with gadolinium-enhancing lesions stabilized.

The final recommended indication therefore excludes patients with gadolinium-enhancing lesions and is considerably narrower than the pediatric and adult population targeted in the new application.

How it works: Leriglitazone is an oral, brain-penetrant activator of PPAR gamma, a receptor involved in inflammation, mitochondrial function and protection from oxidative damage.

cALD causes inflammatory destruction of myelin in the brain and can lead to rapid neurological decline. Stem cell transplantation can stop disease progression in some children, but it is an intensive procedure and is most effective when performed early.

What’s next: The European Commission will make the final authorization decision, which normally follows the CHMP recommendation. Minoryx is also running the placebo-controlled Phase 3 CALYX trial in adult men with progressive cALD, and the TREE Phase 2a trial in pediatric patients with Rett syndrome, with read-outs expected by early 2028 and end of 2026 respectively.