European Commission Approves NEZGLYAL (leriglitazone), First Pharmacological Treatment for Cerebral Adrenoleukodystrophy
核心洞察
The European Commission granted marketing authorisation under exceptional circumstances for NEZGLYAL (leriglitazone) on 21 September 2026, making it the first approved pharmacological treatment for cALD in the EU.
The oral, brain-penetrant selective PPAR gamma (搜索) agonist is indicated for male cALD patients aged 2 to 12 years with Gd-negative brain lesions and a Neurological Functional Score of 0 or 1.
Approval rests on the Phase 2/3 NEXUS study plus real-world compassionate use evidence, with NEXUS showing paediatric patients clinically and radiologically stable beyond 96 weeks of treatment.
The European Commission has granted marketing authorisation under exceptional circumstances for NEZGLYAL (leriglitazone) for the treatment of cerebral adrenoleukodystrophy (搜索) (cALD), making it the first approved pharmacological treatment for the condition in the European Union. The decision, dated 21 September 2026, follows a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) adopted on 23 July 2026.
The approval covers male cALD patients aged 2 to 12 years with non-Gadolinium-enhancing (Gd-negative) lesions on brain magnetic resonance imaging and a Neurological Functional Score (NFS) of 0 or 1. Leriglitazone is an orally bioavailable, brain-penetrant, selective PPAR gamma (搜索) agonist developed by Minoryx Therapeutics (搜索) and licensed exclusively to Neuraxpharm (搜索) for commercialisation in Europe.
Evidence Base and Clinical Data
The authorisation is based on results from the Phase 2/3 NEXUS study, an open-label trial designed to assess the efficacy and safety of leriglitazone in male paediatric patients with early-stage cALD, together with additional real-world evidence from compassionate use programmes. According to the companies, NEXUS results demonstrate that paediatric cALD patients were clinically and radiologically stable after more than 96 weeks of treatment, or at a visit prior to haematopoietic stem cell transplantation (HSCT).
Leriglitazone has also shown clinical benefit in adult cALD patients in the ADVANCE trial, a pivotal Phase 2/3 randomised, double-blind, placebo-controlled study with an open-label extension in male patients with adrenomyeloneuropathy (搜索) (AMN) with or without cALD. Data from ADVANCE showed that leriglitazone reduced cALD progression. More than 170 patients with cALD have received treatment to date.
"With childhood cALD, neurodegeneration is irreversible, so it is critical to halt disease progression early, ideally, before symptoms surface and signs of neuroinflammation appear. Until now, there were no pharmacological treatment options for early intervention," said Dr. Caroline Sevin, MD, PhD, of CRMR LeukoFrance, Hôpital du Kremlin Bicêtre, France. "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. That we now have a pharmacological treatment for early intervention is a major advance in our treatment of cALD."
Disease Burden and Treatment Landscape
cALD is a rapidly progressive neurodegenerative disease characterised by demyelinating brain lesions that can lead to acute neurological decline and death within three to four years. It is an aggressive form of X-linked adrenoleukodystrophy (搜索) (X-ALD), an orphan neurodegenerative disease with a global incidence of approximately 6 to 8 per 100,000 live births. Lesions are initially Gd-negative and become Gadolinium-enhancing as they progress, reflecting damage to the blood-brain barrier. Progression causes loss of voluntary movement, inability to swallow, loss of communication, cortical blindness, total incontinence and death, with a mean survival of three to four years.
cALD with Gd-positive lesions occurs in 31 to 35 percent of ALD patients in childhood, with typical onset between the ages of 2 and 12, and up to 60 percent of adult patients with X-ALD will develop cALD with Gd-positive lesions over time. In childhood, HSCT can arrest the disease, but it is invasive and available only to a portion of patients. Gene therapy-based HSCT is not globally available and requires myeloablative chemotherapy with associated comorbidities. In adults, experience with HSCT is very limited and the intervention is often not recommended. All X-ALD patients reaching adulthood develop AMN, and cALD patients with advanced AMN are largely ineligible for HSCT because of the poor prognosis of the treatment.
NEZGLYAL is taken orally once daily and offers a non-invasive, disease-modifying option for Gd-negative children. The approval is valid across all 27 EU member states, as well as Norway, Iceland and Liechtenstein. Leriglitazone holds orphan drug status for X-ALD from both the FDA and the EMA, and Fast Track and Rare Paediatric Disease designations from the FDA for the treatment of X-ALD.
Launch Plans and Ongoing Development
The first European launch is expected in Germany by the end of the year, with additional launches anticipated pending completion of national reimbursement negotiations. Neuraxpharm (搜索) said it is evaluating appropriate access pathways for eligible patients.
"cALD is a rapidly progressing neurodegenerative disease which severely impacts the lives of patients and their families, underlining the critical need for treatments which can halt or slow disease progression and improve quality of life," said Dr. Jörg Thomas Dierks, CEO of Neuraxpharm (搜索). "Today's announcement reinforces our commitment at Neuraxpharm to advancing innovative medicines that target CNS diseases with significant unmet clinical need."
"This approval represents a significant milestone for the cALD community and recognises years of breakthrough research and collaboration between clinicians and patient organisations," said Marc Martinell, CEO of Minoryx. "Our development efforts continue as we generate more data towards expanding the label within X-ALD and other orphan indications."
The development programme continues beyond the current label. Enrolment is complete in the CALYX Phase 3 trial, a multicentre, randomised 1:1, double-blind, placebo-controlled study of leriglitazone in adult male cALD patients with Gd-positive lesions, with a read-out expected in early 2028. The TREE Phase 2a trial, a randomised 1:1, double-blind, placebo-controlled study evaluating leriglitazone in paediatric female patients with Rett syndrome (搜索), is ongoing with a read-out expected by the end of 2026. Detailed recommendations for the use of NEZGLYAL are described in the Summary of Product Characteristics available on the EMA website in all official EU languages.