Levacetylleucine Explained

Levacetylleucine, sold under the brand name Aqneursa, is a medication used for the treatment of neurological manifestations of Niemann-Pick disease type C.^[1] Levacetylleucine is a modified version of the amino acid leucine (N-Acetyl-L-Leucine). It is taken by mouth.

The most common side effects include abdominal pain, difficulty swallowing, upper respiratory tract infections, and vomiting.

Levacetylleucine was approved for medical use in the United States in September 2024.^{[2] [3]} Levacetylleucine is the second medication approved by the US Food and Drug Administration (FDA) for the treatment of Niemann-Pick disease type C.

Medical uses

Levacetylleucine is indicated for the treatment of neurological manifestations of Niemann-Pick disease type C in people weighing at least 15kg (33lb).

Adverse effects

The most common side effects include abdominal pain, difficulty swallowing, upper respiratory tract infections, and vomiting.

Levacetylleucine may cause embryo-fetal harm if used during pregnancy.

History

The safety and efficacy of levacetylleucine for the treatment of Niemann-Pick disease type C were evaluated in a randomized, double-blind, placebo-controlled, two-period, 24-week crossover study. The duration was twelve weeks for each treatment period. The study enrolled 60 participants. To be eligible for the study participants had to be four years of age or older with a confirmed diagnosis of Niemann-Pick disease type C and at least mild disease-related neurological symptoms. Participants could receive miglustat, an enzyme inhibitor, as background treatment in the study.

The US Food and Drug Administration (FDA) granted the application for levacetylleucine priority review, fast track, orphan drug, and rare pediatric disease designations. The FDA granted approval of Aqneursa to IntraBio Inc.

Society and culture

Legal status

Levacetylleucine was approved for medical use in the United States in September 2024.^[4]

Names

Levacetylleucine is the international nonproprietary name.^[5]

Research

N-Acetyl-L-Leucine is being studied for the treatment of GM2 gangliosidoses (Tay-Sachs and Sandhoff diseases)^[6] and ataxia-telangiectasia.^[7]

Further reading

• Churchill GC, Strupp M, Factor C, Bremova-Ertl T, Factor M, Patterson MC, Platt FM, Galione A . Acetylation turns leucine into a drug by membrane transporter switching . Scientific Reports . 11 . 1 . 15812 . August 2021 . 34349180 . 8338929 . 10.1038/s41598-021-95255-5 . 2021NatSR..1115812C .
• Bremova-Ertl T, Ramaswami U, Brands M, Foltan T, Gautschi M, Gissen P, Gowing F, Hahn A, Jones S, Kay R, Kolnikova M, Arash-Kaps L, Marquardt T, Mengel E, Park JH, Reichmannová S, Schneider SA, Sivananthan S, Walterfang M, Wibawa P, Strupp M, Martakis K . Trial of N-Acetyl-l-Leucine in Niemann-Pick Disease Type C . The New England Journal of Medicine . 390 . 5 . 421–431 . February 2024 . 38294974 . 10.1056/NEJMoa2310151 .
• Tifft CJ . N-Acetyl-l-Leucine and Neurodegenerative Disease . The New England Journal of Medicine . 390 . 5 . 467–470 . February 2024 . 38294981 . 10.1056/NEJMe2313791 .

Notes and References

1. Web site: Aqneursa- levacetylleucine granule, for suspension . DailyMed . 24 September 2024 . 5 October 2024.
2. FDA Approves New Drug to Treat Niemann-Pick Disease, Type C . U.S. Food and Drug Administration . 24 September 2024 . 25 September 2024.
3. IntraBio Announces U.S. FDA Approval of Aqneursa for the Treatment of Niemann-Pick Disease Type C . IntraBio . 25 September 2024 . 26 September 2024.
4. Web site: Novel Drug Approvals for 2024 . U.S. Food and Drug Administration (FDA) . 1 October 2024 . 29 November 2024.
5. ((World Health Organization)) . 2024 . International nonproprietary names for pharmaceutical substances (INN): proposed INN: list 131 . WHO Drug Information . 38 . 2 . 10665/378367 . free . World Health Organization . 9789240098558 .
6. Martakis K, Claassen J, Gascon-Bayari J, Goldschagg N, Hahn A, Hassan A, Hennig A, Jones S, Kay R, Lau H, Perlman S, Sharma R, Schneider S, Bremova-Ertl T . Efficacy and Safety of N-Acetyl-l-Leucine in Children and Adults With GM2 Gangliosidoses . Neurology . 100 . 10 . e1072–e1083 . March 2023 . 36456200 . 9990862 . 10.1212/WNL.0000000000201660 .
7. Fields T, Patterson M, Bremova-Ertl T, Belcher G, Billington I, Churchill GC, Davis W, Evans W, Flint S, Galione A, Granzer U, Greenfield J, Karl R, Kay R, Lewi D, Mathieson T, Meyer T, Pangonis D, Platt FM, Tsang L, Verburg C, Factor M, Strupp M . A master protocol to investigate a novel therapy acetyl-L-leucine for three ultra-rare neurodegenerative diseases: Niemann-Pick type C, the GM2 gangliosidoses, and ataxia telangiectasia . Trials . 22 . 1 . 84 . January 2021 . 33482890 . 7821839 . 10.1186/s13063-020-05009-3 . free .