The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending approval of Aqneursa (levacetylleucine) for the treatment of neurological manifestations of Niemann-Pick type C (NPC) disease in adults and children aged six years and older weighing at least 20 kg. The drug should be used in combination with miglustat, or as monotherapy in patients where miglustat is not tolerated.
Clinical Trial Results Drive Recommendation
The CHMP recommendation is based on results from a randomized, double-blind, placebo-controlled, 2-period crossover study involving 60 patients. The trial measured neurological signs, symptoms and functioning using the Scale for the Assessment and Rating of Ataxia (SARA), which evaluates walking, standing, sitting and speech capabilities. Of the 60 participants, 51 were already receiving miglustat and continued treatment during the study.
Patients were randomized in a 1:1 ratio to receive either Aqneursa or placebo for 12 weeks in Period I, then switched to the opposite treatment for another 12 weeks in Period II. At the end of Period I, patients treated with Aqneursa demonstrated statistically significant improvement in SARA scores compared to those receiving placebo.
The crossover design provided additional validation of the drug's efficacy. Patients who switched from Aqneursa to placebo in Period II experienced significant worsening of symptoms compared to their SARA scores at the end of Period I. Notably, patients not receiving miglustat also showed improved SARA scores when treated with Aqneursa.
Addressing Critical Unmet Medical Need
NPC is a rare, progressive, and fatal genetic disorder caused by mutations encoding lysosomal proteins essential for intracellular transport and metabolism of body fats, including cholesterol. Over time, cells of the central nervous system and body organs stop functioning properly. The disease course varies highly depending on age of onset, but most NPC patients are children who die before age 20.
Currently, there are no curative therapies for NPC. Miglustat is the only medicine previously authorized to treat NPC and has been shown to slow general progression of neurological symptoms in patients, highlighting the significant unmet medical need in this patient population.
Mechanism of Action and Safety Profile
Levacetylleucine is a modified form of the amino acid leucine, which plays a vital role in protein synthesis, muscle growth, and tissue regeneration. The drug targets underlying processes of neurological dysfunction. Nonclinical studies have demonstrated that levacetylleucine corrects energy metabolism and improves production of adenosine triphosphate, the main source of energy for cerebellar tissues and cells.
The safety profile appears favorable, with flatulence being the only adverse event causally related to Aqneursa treatment in the clinical trial.
Global Regulatory Progress
Dr. Marc Patterson, Chief Medical Officer of IntraBio, stated: "This positive CHMP opinion represents another important milestone in expanding access to AQNEURSA to the global NPC community. The recommendation reflects the strength of our clinical data and the potential for AQNEURSA to be a foundational therapy for NPC, delivering meaningful benefits for patients."
Aqneursa previously received U.S. FDA approval in September 2024 for treating neurological manifestations of NPC in adults and pediatric patients weighing ≥15 kg. Since U.S. approval, the drug has experienced rapid adoption as a frontline therapy for NPC with continued growth in demand.
Patient Community Response
Carmelo Fernández, President of Fundación Niemann-Pick de España, expressed optimism about the development: "For NPC families like mine, this positive opinion brings long-awaited hope for a treatment that can actually offer improvements. We have waited years for a therapy that can make a meaningful difference in the lives of people with NPC, and today's announcement brings us one step closer."
Next Steps and Future Development
The CHMP opinion will now be sent to the European Commission for adoption of a decision on EU-wide marketing authorization. Once marketing authorization is granted, decisions about price and reimbursement will occur at the individual Member State level, considering the potential role of the medicine within each country's national health system.
IntraBio remains on track to proceed with additional global regulatory submissions for Aqneursa in 2025 and beyond. The company is also advancing its pipeline, with a Phase III trial investigating N-Acetyl-L-Leucine for Ataxia-Telangiectasia having completed recruitment and over-enrolled by 167%, with data readout expected in Q1 2026.
