Extended success for N-acetyl-L-leucine in Niemann-Pick disease type C

The 12-month data from the IB1001-301 study revealed a marked reduction in disease progression with N-acetyl-L-leucine (NALL) compared with placebo in patients with Niemann-Pick disease type C. NALL was efficacious irrespective of background miglustat treatment and well-tolerated in the study population.

“NALL is a chemically modified amino acid which induces the normalisation of mitochondrial function with knock-on effects, including normalisation of lysosomal function, inter-ion cellular signalling, and dampening neuroinflammation,” explained Dr Tatiana Bremova-Ertl (University Hospital Bern, Switzerland).

The phase 3 IB1001-301 study (NCT05163288) randomised 60 patients with Niemann-Pick disease type C to 12 weeks of therapy with NALL or a placebo, after which participants crossed over to the other arm to receive another 12 weeks of therapy. Participants could enter the extension phase of the trial after the randomised period had ended. The primary and secondary efficacy endpoints were met at 12 and 24 weeks and the agent was well-tolerated [1]. Dr Bremova-Ertl presented the findings after 12 months of follow-up in the extension period [2].

At month 12, the Niemann-Pick type C Clinical Severity Scale (NPCCSS) was slightly improved in participants receiving NALL (-0.12) whereas a historical cohort showed that the scores of patients not receiving NALL worsened over this period (+1.50). “This difference corresponds to a 108% reduction in annual disease progression,” noted Dr Bremova-Ertl. Moreover, NALL was efficacious, regardless of miglustat background therapy. Finally, the improvement in the Scale for Assessment and Rating of Ataxia (SARA) score that was found after the randomised period (mean change from baseline -1.97) was maintained during the extension phase of the study (mean change from baseline -1.92).

“Based on the positive findings from IB1001-301, the extension phase is open to recruiting new patients with Niemann-Pick disease type C to further evaluate NALL,” Dr Bremova-Ertl concluded.

1. Bremova-Ertl T, et al. N Engl J Med 2024;390:421-431
2. Bremova-Ertl T, et al. Long-term findings of N-acetyl-L-leucine for Niemann-Pick disease type C. 10th EAN Congress, 29 June–2 July 2024, Helsinki, Finland.

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Posted on 25 July 202425 July 2024