AQNEURSA Granules for oral suspension Ref.[116287] Active ingredients: Levacetylleucine

Pharmacotherapeutic group: Other nervous system drugs
ATC code: N07XX27

Pharmacodynamic effects

Aqneursa contains levacetylleucine that targets underlying processes of neurological dysfunction. Nonclinical studies demonstrated that levacetylleucine corrects energy metabolism, including improving adenosine triphosphate production.

Clinical efficacy and safety

The efficacy and safety of levacetylleucine for treatment of NPC was studied in a randomised, double- blind, placebo-controlled, 2-period crossover study that evaluated the efficacy of levacetylleucine in NPC patients. To be eligible for the study, patients had to be aged 4 years or older with a confirmed diagnosis of NPC, a baseline SARA score of 7 to 34 points, and not receiving any other investigational therapies; patients were permitted to be receiving treatment with miglustat.

Patients were randomised in a 1:1 ratio to receive either levacetylleucine or placebo for 12 weeks in Period I. In Period II, patients switched to the opposite (either levacetylleucine or placebo) for 12 weeks. Patients aged ≥ 13 years received 4 g/day (as 2 g morning dose, 1 g afternoon dose and 1 g evening dose). The levacetylleucine dose in children under 13 years was based on patient's body weight (see section 4.2).

A total of 60 patients were randomised and treated, and 59 (98%) completed both treatment periods with levacetylleucine and placebo.

Of the 60 randomised patients (37 adults and 23 paediatric patients), 27 were female and 33 were male. The median age at treatment initiation was 25 years (range: 5 to 67 years). 90% of the patients were White, 3% Asian and 7% Other. In total, 51 (85%) patients received miglustat treatment prior to randomisation and during the study.

The primary endpoint measure was the measurement of neurological signs, symptoms and functioning as measured by the Scale for the Assessment and Rating of Ataxia (SARA).

The SARA assessment was carried out at baseline and then assessed at the end of Period I (Week 12) and the end of Period II (Week 24). Treatment with levacetylleucine demonstrated a statistically significant difference in favour of levacetylleucine as compared to placebo on SARA (Table 3).

Table 3. Summary of scale for the assessment and rating of ataxia (SARA) efficacy results*:

CI = confidence interval; SD = standard deviation; SE = standard error.
^* The change from baseline was assessed at the end of Period 1 (Week 12) and the end of Period 2 (Week 24).
^** Two-sided p-value

The 30 patients receiving placebo in Period I had no meaningful change in the mean SARA score of -0.60 compared to those on levacetylleucine, who had a substantial change of -1.93. The remaining 30 patients who received levacetylleucine in Period I followed by placebo in Period II experienced significant worsening of symptoms on placebo, which effectively served as a washout from levacetylleucine (difference in mean SARA score between the end of Period I [Week 12] and the end of Period II [Week 24] of +1.55), reflecting a deterioration in neurological signs and symptoms when treatment with levacetylleucine was stopped (Figure 1).

In total, 9 patients (15%) were not on miglustat prior to randomisation and during the study. In these patients, there was also a change in the mean SARA score on levacetylleucine of -2.06.

Figure 1. Individual patient SARA total scores at baseline, end of Period I, and End of Period II:

Paediatric population

The European Medicines Agency has deferred the obligation to submit the results of studies with levacetylleucine in one or more subsets of the paediatric population in the treatment of Niemann-Pick disease, type C (see section 4.2 for information on paediatric use).