Long-Term 30-Month Results of N-Acetyl-L-Leucine for Niemann-Pick Disease Type C
Michael Strupp1, Marc Patterson2, Bethany Zanrucha2, Janelle Raymond2, Asante Hatcher2, Jorgji Kerthi2, Taylor Fields2, Ian Billington2, Tatiana Bremova-Ertl3
1Department of Neurology, LMU University Hospital, 2IntraBio, Inc., 3Department of Neurology and Center for Rare Diseases, University Hospital Inselspital Bern
Objective:
To evaluate the long-term effects of N-acetyl-L-leucine (NALL) in people with Niemann-Pick disease type C (NPC).
Background:
NPC is a rare autosomal recessive neurodegenerative lysosomal storage disorder. IB1001-301 is a Phase 3, double-blind, randomized, placebo-controlled, crossover trial evaluating NALL for the treatment of neurological signs and symptoms in NPC encompassing a Parent Study and open-label Extension Phase (EP). The global primary endpoint of the Parent Study, the Scale for the Assessment and Rating of Ataxia (SARA), was reduced -1.97 points with NALL and -0.60 with placebo (P<0.001) after 12 weeks. Following the Parent Study, extended follow-up data were obtained to evaluate the long-term effects of NALL for NPC.
Design/Methods:
Participants received treatment with orally administered NALL 2-3 times per day (participants 4-12 years receiving weight-based doses [2-4 g per day]; those ≥ 13 years 4 g per day). The primary endpoint of the EP is the modified 5-domain NPC Clinical Severity Scale (NPC-CSS, range 0-25). Comparisons were made to the expected annual trajectory of disease decline established in published natural history studies (henceforth referred to as the historical cohort). Exploratory endpoints included the 15-domain NPC-CSS (excluding hearing) and SARA.
Results:
Fifty-four participants aged 5 to 67 years were treated in the EP. The interim 24-month mean (±SD) change from baseline on the 5-domain NPC-CSS was -0.32 (±2.66) on NALL, i.e., improvement, compared to 3.0 (±6.32) in the historical cohort: mean difference -3.32. Results of the 15-domain NPC-CSS were supportive of the primary analysis and improvements in neurological status as measured by SARA were sustained over the 24-month follow-up. No drug-related TEAEs, SAEs, or deaths occurred during the study. Long-term 30-month data will be presented at the 2026 American Academy of Neurology pending data availability.
Conclusions:
Long-term 24-month treatment with NALL has demonstrated statistically significant and clinically meaningful reduction in disease progression.
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