N-Acetyl-L-Leucine Reduces Disease Progression in Phase 2 Extension Study for Ataxia-Telangiectasia

New late-breaking data presented at the 2025 International Congress of Parkinson’s Disease and Movement Disorders (MDS), held October 5-9, in Honolulu, Hawaii, from the extension of the phase 2 IB1001-203 trial (NCT03759678) showed that treatment with N-acetyl-L-leucine (NALL) slowed disease progression in patients with ataxia-telangiectasia (A-T), suggesting potential neuroprotective and disease-modifying effects. Following these positive results, researchers have initiated a global phase 3 study (NCT06673056), dubbed IB1001-303, to further assess the investigational therapy in A-T.¹

The extension phase involved 12 patients aged 6 to 36 years who continued NALL treatment following the initial phase 2 study. After 12 months of treatment, those on the agent demonstrated a mean change from baseline of -2.25 points (SD, 3.16) on the Scale for the Assessment and Rating of Ataxia (SARA)(95% CI, -4.25 to-0.25; P = .031). During a subsequent washout period, the mean change was 1.36 (SD, 2.04) in SARA (95% CI, 0-2.73; P = .25) for participants (n = 11). Notably, 7 patients completed an additional year of NALL treatment after the washout period, with a mean change of −0.33 points in SARA score compared with the start of the extension phase.

Presented by lead author Marc C. Patterson, MD, FRACP, FAAN, FANA, chief medical officer at IntraBio, IB1001-203 was a phase 2 trial assessing NALL in patients at least 6 years with A-T. After the initial study, participants had the option to continue treatment in the extension phase of the trial. In the extension phase, the primary end point was the change from baseline compared with the end of the first year of treatment with NALL, as measured by SARA. Exploratory end points of the extension phase included the change in SARA change during the washout period and the change from the end of the second year of treatment with NALL in comparison with baseline.

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NALL, a modified amino acid, enters enzyme-controlled pathways and aims to correct metabolic dysfunction, improve lysosomal and mitochondrial function, and restore membrane potential and cellular signaling. In the extension phase of the IB1001-203 trial, findings revealed that treatment with NALL corresponded to a 340% reduction in annual disease progression following 1 year and 120% following 2 years compared with a natural history control cohort.

Investigators are continuing to assess NALL for the treatment of A-T in the phase 3 IB1001-303 study, using SARA as the primary end point. The trial features a randomized, placebo-controlled, double-blind crossover phase, followed by a long-term open-label extension. Developed in collaboration with leading experts and A-T patient organizations, the study aims to evaluate both symptomatic benefits and longer-term clinical outcomes. Results from the IB1001-303 trial are expected to be reported in the first quarter of 2026.²

In a prior phase 3 trial (NCT05163288), treatment with NALL significantly reduced neurologic signs and symptoms, including ataxia, over 12 weeks among 60 patients aged between 5 and 67 years with Niemann-Pick disease type C (NPC). Published in the New England Journal of Medicine, investigators observed a mean change from baseline in the total score on SARA) of −1.97 (SD, 2.43) points following 12 weeks of receiving NALL and −0.60 (SD, 2.39) points after 12 weeks of receiving placebo (least-squares mean difference, −1.28 points; 95% CI, −1.91 to −0.65; P <.001).³

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REFERENCES
1. Patterson M, Zanrucha B, Raymond J, et al. N-acetyl-L-leucine: Findings from the Extension Phase of a Phase II Clinical Trial in Ataxia-Telangiectasia. Presented at: 2024 MDS Congress; October 5-9; Honolulu, Hawaii. LBA-4.
2. IntraBio Inc. Completes Recruitment for IB1001 A-T Pivotal Clinical Trial. News Release. IntraBio. Published July 1, 2025. Accessed ctober 6, 2025. https://www.businesswire.com/news/home/20250701009060/en/IntraBio-Inc.-Completes-Recruitment-for-IB1001-A-T-Pivotal-Clinical-Trial
3. Bremova-Ertl T, Ramaswami U, Brands M, et al. Trial of N-Acetyl-l-Leucine in Niemann-Pick Disease Type C. N Engl J Med. 2024;390(5):421-431. doi:10.1056/NEJMoa2310151