Minoryx Therapeutics and Neuraxpharm Group have secured a positive recommendation from the European Medicines Agency’s Committee for Medicinal Products for Human Use for NEZGLYAL, or leriglitazone, in a narrowly defined group of boys with cerebral adrenoleukodystrophy. The proposed indication covers males aged two to 12 years with non-gadolinium-enhancing brain lesions and a Neurological Functional Score of zero or one, identifying patients at an early clinical stage before severe neurological deterioration has developed. The committee recommended marketing authorisation under exceptional circumstances, and the companies expect a European Commission decision by the end of September 2026. The opinion could lead to the first approved pharmacological treatment for cerebral adrenoleukodystrophy in the European Union, although the recommendation does not cover older patients, gadolinium-enhancing lesions or advanced neurological disease.
Why the proposed NEZGLYAL indication focuses on early non-gadolinium-enhancing brain lesions
Cerebral adrenoleukodystrophy is an inflammatory neurological form of X-linked adrenoleukodystrophy in which abnormal accumulation of very-long-chain fatty acids contributes to damage of myelin, the protective covering around nerve fibres in the brain. Lesions may initially appear on magnetic resonance imaging without gadolinium enhancement and can later become gadolinium-enhancing as inflammation progresses and the blood-brain barrier becomes disrupted. Once the disease accelerates, patients can lose movement, swallowing ability, communication and vision, with progressive disease potentially leading to death within several years.
The recommended population is limited to boys with non-gadolinium-enhancing lesions and Neurological Functional Scores of zero or one. A low Neurological Functional Score indicates that a patient has no measurable neurological deficit or only minimal impairment. The proposed label therefore targets a window in which brain lesions have been detected but severe clinical decline has not yet occurred.
That early-treatment focus is clinically important because available evidence suggests that interventions for cerebral adrenoleukodystrophy are more effective before extensive neurological damage develops. Haematopoietic stem cell transplantation can arrest disease progression in selected children, but it requires donor identification, conditioning chemotherapy and a complex transplant procedure carrying risks that include infection, organ complications, graft failure and death. Some children may not have an appropriate donor or may progress while waiting for treatment.
Leriglitazone would provide a non-invasive, once-daily oral option that could potentially be started when early brain lesions are identified. It is not being presented as a replacement for transplantation in every eligible patient. Its eventual role will depend on the final European label, treatment guidelines, comparative experience and whether physicians use it as an alternative, a bridge to transplantation or part of an earlier intervention strategy.
The narrow age and imaging criteria also prevent the positive opinion from being interpreted as validation across the entire X-linked adrenoleukodystrophy population. Boys with gadolinium-enhancing lesions, adults with cerebral disease and patients with more advanced neurological impairment remain outside the recommended indication. Minoryx Therapeutics is continuing separate studies intended to generate evidence in additional populations.
How the open-label NEXUS study supported the leriglitazone European recommendation
The positive opinion was primarily supported by the NEXUS Phase 2/3 study and additional real-world evidence from compassionate-use programmes. NEXUS was a 96-week, open-label, multicentre study evaluating once-daily oral leriglitazone in children with cerebral adrenoleukodystrophy. Twenty-three patients entered the trial, while the evaluable population included 20 patients who received treatment for at least 24 weeks.
All 20 evaluable patients remained clinically stable while receiving treatment. Seven patients, representing 35% of the evaluable population, met the trial’s combined criteria for clinically and radiologically arrested disease. The study compared that proportion with an expected spontaneous arrest rate of 10% derived from natural-history evidence, and the difference met the prespecified statistical criterion. No treatment-related serious adverse events or treatment-related discontinuations were reported in the completed study.
These findings are encouraging because untreated progressive cerebral adrenoleukodystrophy can move rapidly from detectable lesions to irreversible neurological injury. Demonstrating clinical stability alongside controlled lesion progression over an extended period suggests that leriglitazone may influence the underlying disease process rather than only treating symptoms.
The evidence nevertheless carries important limitations. NEXUS did not randomly assign patients to leriglitazone or placebo, and it did not include a concurrent untreated control group. The primary comparison relied partly on natural-history expectations, which can be affected by differences in screening, imaging schedules, disease stage and patient selection. The small evaluable population also makes uncommon safety events and variation in treatment response harder to characterise.
The recommendation under exceptional circumstances reflects these realities. The European Medicines Agency uses this route when comprehensive evidence cannot reasonably be obtained, including situations involving extremely rare diseases or populations in which conventional large trials may be impractical or ethically difficult. Unlike a conditional marketing authorisation, approval under exceptional circumstances generally does not assume that a complete conventional data package will later become available, although the marketing authorisation holder remains subject to ongoing evidence, safety-monitoring and regulatory obligations.
More than 170 patients with cerebral adrenoleukodystrophy have received leriglitazone across clinical studies and treatment programmes, according to the companies. The broader programme includes evidence from ADVANCE, compassionate use and ongoing studies, but the European recommendation remains tied to the specific pediatric population supported most directly by the NEXUS data.
What leriglitazone’s earlier European refusal reveals about the narrower second application
The July 2026 recommendation follows an earlier European regulatory setback. In January 2024, the Committee for Medicinal Products for Human Use recommended refusing a previous application for NEZGLYAL that sought treatment across pediatric and adult male patients aged two years and older with cerebral adrenoleukodystrophy. The negative opinion was confirmed after re-examination in May 2024.
That earlier submission relied heavily on evidence from the ADVANCE study in adult men with adrenomyeloneuropathy. ADVANCE did not meet its primary endpoint involving change in six-minute walking distance, although secondary cerebral findings suggested that leriglitazone reduced the development and progression of brain lesions. Cerebral lesions developed or worsened in 21% of placebo-treated patients compared with 4% of leriglitazone-treated patients, while no leriglitazone patients developed cerebral adrenoleukodystrophy compared with 15% of placebo recipients.
The new application was built around the completed NEXUS study and focused on a more precisely defined pediatric population. Rather than attempting to support a broad label spanning children and adults with different disease stages, Minoryx Therapeutics submitted evidence for boys aged two to 12 with early, non-enhancing lesions and minimal neurological impairment. This narrower strategy appears to have addressed at least part of the uncertainty that undermined the previous application.
The regulatory reversal is meaningful but should not be described as the European Medicines Agency changing its mind about the same evidence and indication. The 2026 positive opinion concerns a new marketing application supported by additional pediatric results and a substantially narrower proposed population. The earlier refusal remains relevant because it demonstrates that regulators were unwilling to extrapolate the available evidence broadly across cerebral adrenoleukodystrophy.
Safety monitoring will remain important if the European Commission approves the medicine. Earlier adult studies associated leriglitazone with weight gain and peripheral oedema, effects consistent with pharmacological activation of peroxisome proliferator-activated receptor gamma. The pediatric NEXUS study did not report treatment-related serious adverse events or discontinuations, but real-world use could expose a larger and more diverse population for longer periods.
What European approval could mean for Minoryx Therapeutics and Neuraxpharm Group
Minoryx Therapeutics discovered and developed leriglitazone, while Neuraxpharm Group holds exclusive European commercial rights. Neuraxpharm Group would be responsible for bringing the therapy to European markets following European Commission approval, although launch timing will also depend on pricing, reimbursement and national access decisions across individual countries.
A European authorisation would establish the first commercial validation of Minoryx Therapeutics’ selective, brain-penetrant peroxisome proliferator-activated receptor gamma platform. Leriglitazone is designed to influence pathways associated with neuroinflammation, mitochondrial function, oxidative stress, myelination and neuronal survival. The mechanism may have relevance beyond cerebral adrenoleukodystrophy, but those additional uses remain investigational.
The companies are continuing the CALYX Phase 3 trial in adult men with gadolinium-enhancing cerebral adrenoleukodystrophy. That randomized, placebo-controlled study is intended to support possible label expansion and broader regulatory development, with results expected by early 2028. Minoryx Therapeutics is also studying leriglitazone in the Phase 2a TREE trial for pediatric Rett syndrome, with a readout expected by the end of 2026.
The current positive opinion does not guarantee European Commission approval, although the Commission generally follows the scientific recommendation of the Committee for Medicinal Products for Human Use. The final decision will determine the authorised indication, prescribing information, safety requirements and obligations attached to the exceptional-circumstances approval.
For families affected by cerebral adrenoleukodystrophy, the most important potential change is the availability of an oral pharmacological intervention during an early disease window in which neurological function may still be preserved. The narrow recommendation leaves significant unmet need outside the indicated population, but it represents a substantial regulatory advance after the broader application was refused in 2024.
The remaining clinical challenge is to establish how durable disease stabilisation remains over longer follow-up and where leriglitazone should sit relative to transplantation and gene therapy. The European opinion supports use in a carefully selected group rather than a universal cerebral adrenoleukodystrophy treatment, making early diagnosis, regular magnetic resonance imaging and precise patient selection central to its eventual clinical impact.
