EMA Clears One Rare Brain Disease Therapy, Rejects Another

Two orphan medicines for severe childhood neurologic conditions received opposite decisions from the European Medicines Agency (EMA). At its July 2026 meeting, the Committee for Medicinal Products for Human Use (CHMP) recommended approval under exceptional circumstances for Nezglyal (leriglitazone, Minoryx Therapeutics), but rejected Meplyffa (arimoclomol, Zevra Denmark), citing insufficient evidence of efficacy. The positive opinion covers boys aged 2-12 years with cerebral adrenoleukodystrophy (cALD) who have non-gadolinium-enhancing brain lesions on MRI and a Neurological Functional Score of 0 or 1. Meanwhile, Meplyffa was turned down for Niemann-Pick disease type C after regulators raised concerns over the robustness of the efficacy data.NezglyalCerebral adrenoleukodystrophy is the inflammatory cerebral form of adrenoleukodystrophy and can cause rapid neurologic decline in affected boys.Leriglitazone, an active metabolite of pioglitazone, is a selective peroxisome proliferator-activated receptor gamma agonist that crosses the blood-brain barrier and is intended to reduce neuroinflammation while supporting myelin integrity and mitochondrial function.CHMP based its recommendation on an open-label study involving 20 evaluable boys with cALD treated for up to 96 weeks or until hematopoietic stem cell transplantation. Overall, 35% of patients experienced no clinically meaningful neurologic or radiologic progression during treatment.Outcomes appeared most favorable among patients with earlier-stage disease. Among boys with non-gadolinium-enhancing lesions at baseline, 66.7% achieved disease stabilization compared with only 9.1% of those with gadolinium-enhancing lesions. According to the CHMP, these stabilization rates exceeded those expected from the natural history of the disease.The most frequently reported adverse events in the pediatric study were weight gain, eyelid edema, and reduced white blood cell counts.If the European Commission grants marketing authorization, Nezglyal will be available as an oral suspension (13.66 mg/mL) for eligible boys with early-stage cALD. Treatment should be initiated and monitored by physicians experienced in managing neurodegenerative disorders.Detailed prescribing guidance will appear in the Summary of Product Characteristics after European Commission authorization. MeplyffaNiemann-Pick disease type C is a rare inherited lysosomal disorder caused by mutations affecting intracellular lipid transport, resulting in progressive neurologic deterioration. Arimoclomol is designed to enhance activation of the cellular proteins TFEB and TFE3, promoting the production of proteins involved in lipid clearance and reducing the accumulation of harmful fats within cells.Meplyffa was evaluated in a placebo-controlled study of 50 children and adolescents with Niemann-Pick disease type C who received treatment for one year alongside standard care, including miglustat for most participants. The primary endpoint was change in the five-domain Niemann-Pick disease Type C Severity Scale. The EMA said the submitted data did not sufficiently demonstrate efficacy and that no benefit was seen in ambulation or cognition. It also cited significant concerns regarding data handling and analysis reliability. Although a subgroup receiving concurrent miglustat showed a treatment effect favoring Meplyffa, the overall study failed to establish robust clinical efficacy.