EC approves leriglitazone as first pharmacological cALD treatment
The European Commission has granted marketing authorisation under exceptional circumstances for NEZGLYAL (leriglitazone), making it the first approved pharmacological treatment for cerebral adrenoleukodystrophy (cALD) in the European Union. The decision, effective across all 27 EU member states plus Norway, Iceland and Liechtenstein, covers male patients aged 2 to 12 with Gadolinium-negative brain lesions and a Neurological Functional Score of 0 or 1. The authorisation is held jointly by Neuraxpharm Group, which will commercialise the product in Europe, and Minoryx Therapeutics, which developed the compound.
Leriglitazone is an orally bioavailable, brain-penetrating, selective PPAR gamma agonist taken as a daily oral dose. The EC's decision is based on results from the Phase 2/3 NEXUS study, in which paediatric cALD patients remained clinically and radiologically stable after more than 96 weeks of treatment or ahead of haematopoietic stem cell transplantation (HSCT), and from compassionate-use data. More than 170 patients have received the drug to date. Neuraxpharm plans to launch in Germany before the end of 2026, with further European markets to follow subject to national reimbursement negotiations.
Filling a critical treatment gap
cALD is an aggressive manifestation of X-linked adrenoleukodystrophy (X-ALD), a rare hereditary disorder with a global incidence of roughly 6 to 8 per 100,000 live births. In the cerebral form, demyelinating brain lesions can progress rapidly and, without intervention, lead to severe neurological disability and death within three to four years of onset. Until now, the only recognised intervention was HSCT, which is invasive, donor-dependent, and applicable only within a narrow window before lesions become Gadolinium-enhancing. Gene therapy-based HSCT exists but is not globally accessible and requires myeloablative conditioning.
Caroline Sevin, a specialist at CRMR LeukoFrance, Hopital du Kremlin Bicetre, said the absence of pharmacological options had made early intervention impossible: "Until now, there were no pharmacological treatment options for early intervention. That we now have a pharmacological treatment for early intervention is a major advance in our treatment of cALD."
Competitive landscape and pipeline
The rare paediatric neurodegeneration space has attracted growing attention from both specialist CNS-focused companies and larger pharmaceutical groups seeking orphan-drug incentives. For cALD specifically, the approved label is narrow and the patient population small, meaning any expansion of the indication or the age range would materially change the commercial profile of the asset.
Minoryx is already pursuing that expansion. Enrolment is complete in the CALYX Phase 3 trial evaluating leriglitazone in adult male cALD patients with Gadolinium-enhancing lesions, with a readout expected in early 2028. A separate Phase 2a programme, TREE, is assessing the compound in paediatric girls with Rett syndrome, with data anticipated by the end of 2026. The FDA has granted leriglitazone orphan drug status for X-ALD, alongside Fast Track and Rare Paediatric Disease designations, preserving a potential US regulatory pathway should the clinical data support a filing.
The authorisation under exceptional circumstances reflects the limited size of the evidence base available at approval, a standard EMA route for rare diseases where conducting large randomised trials is impractical. Payers across Europe are likely to scrutinise the clinical dataset carefully during reimbursement negotiations, particularly given the open-label design of the NEXUS study and the absence of a placebo-controlled comparator arm in the paediatric population. How quickly Neuraxpharm can secure favourable reimbursement terms in key markets such as France, Italy and Spain will determine how rapidly the drug reaches the children for whom it is indicated.