NPC is a rare, autosomal recessive lysosomal disease. IB1001-301, a Phase III, double-blind, randomized, placebo-controlled 12-week clinical trial compared levacetylleucine with placebo for treating neurological signs and symptoms in NPC. The parent study met its primary (SARA) and all secondary endpoints (including mDRS) in 60 patients aged 5 to 67.

To evaluate the efficacy of levacetylleucine compared to placebo across subdomains of the modified Disability Rating Scale (mDRS), in adult and pediatric subgroups within the Scale for the Assessment and Rating of Ataxia (SARA) and investigate long-term findings from IB1001-301.

Subgroup analysis was conducted of the SARA to evaluate the effects of levacetylleucine in pediatric ( <18 years) and adult ( ≥ 18 years) patients. Among the whole population, the subdomains of the mDRS were evaluated to determine treatment effect of levacetylleucine versus placebo across different neurological domains. Follow-up data from the ongoing open-label extension phase evaluated the long-term, neuroprotective effects of levacetylleucine. 

Improvement in pediatric and adult patients treated with levacetylleucine was superior to placebo with a mean difference of -1.8 points and -1.1 points, respectively, on the SARA.

On each mDRS domain there was improvement from baseline when patients received levacetylleucine and a greater improvement in each domain when patients were treated with levacetylleucine versus placebo

54 patients aged 5 to 67 years have been treated in the EP. After 18 months, the mean (±SD) change from baseline on the 5-domain NPC-CSS was -0.067 (±2.94) and 2.25±4.74 in the historical cohort (mean difference 2.32; 95% Confidence Interval, 0.46 to 4.17; p=0.017). 

Levacetylleucine demonstrated a significant improvement over placebo in pediatric and adult patients on the SARA and consistent improvement across mDRS subdomains. Treatment with levacetylleucine after 18 months was associated with a clinically significant reduction in disease progression consistent with a neuroprotective and disease-modifying effect.