New treatment for Niemann-Pick type C disease
Aqneursa significantly improves neurological signs, symptoms and functioning
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EMA has recommended granting a marketing authorisation in the European Union (EU) for Aqneursa (levacetylleucine) for the treatment of neurological manifestations of Niemann-Pick type C (NPC) disease in adults and children aged six years and older and weighing at least 20 kg. Aqneursa should be used in combination with miglustat, or as a monotherapy in patients where miglustat is not tolerated.
NPC is a rare, progressive, and fatal genetic disorder caused by mutations encoding lysosomal proteins that are essential for the intracellular transport and metabolism of body fats, including cholesterol. Over time, the cells of the central nervous system and the body organs stop working. The course of the disease varies highly depending on the age of onset, but most NPC patients are children and die before the age of 20. There are no curative therapies for NPC. Miglustat is the only medicine authorised to treat NPC and has been shown to slow the general progression of neurological symptoms in patients.
Levacetylleucine is a modified form of the amino acid leucine, which plays a vital role in protein synthesis, muscle growth, and tissue regeneration. Levacetylleucine targets underlying processes of neurological dysfunction. Nonclinical studies have demonstrated that levacetylleucine corrects energy metabolism and improves the production of adenosine triphosphate, the main source of energy for the cerebellar tissues and cells.
The recommendation is based on the results of a randomised, double-blind, placebo-controlled, 2-period crossover study in 60 patients whose neurological signs, symptoms and functioning were measured using the Scale for the Assessment and Rating of Ataxia (SARA), including walking, standing, sitting and speech. Of these 60 patients, 51 were already receiving miglustat and continued to receive it during the study. Patients were randomised in a 1:1 ratio to receive either Aqneursa or placebo for 12 weeks in Period I. In Period II, patients were switched to the opposite (either Aqneursa or placebo) for another 12 weeks.
At the end of Period I, patients treated with Aqneursa demonstrated a statistically significant improvement in the SARA score compared to those treated with placebo. At the end of Period II, patients who switched from Aqneursa to placebo experienced a significant worsening of symptoms compared to their SARA score at the end of Period I. Patients not receiving miglustat also improved their SARA score when treated with Aqneursa.
The only adverse event that has been causally related to treatment with Aqneursa is flatulence.
The opinion adopted by the CHMP is an intermediary step on Aqneursa’s path to patient access. The opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorisation. Once a marketing authorisation has been granted, decisions about price and reimbursement will take place at the level of each Member State, taking into account the potential role or use of this medicine in the context of the national health system of that country.
Notes
- The applicant for Aqneursa is IntraBio Ireland Ltd.
- Aqneursa was designated as an orphan medicinal product on 20 March 2017 for treatment of treatment of Niemann-Pick disease. Following this positive CHMP opinion, the Committee for Orphan Medicinal Products (COMP) will assess whether the orphan designation should be maintained.