A Dose-escalation and Safety & Efficacy Study of AXO-AAV-GM2 in Tay-Sachs or Sandhoff Disease

Summary

The AXO-GM2-001 study is an open-label, two-stage clinical trial designed to evaluate safety and dose-escalation (Stage 1) and safety and efficacy (Stage 2) of a bilateral thalamic and intracisternal/intrathecal infusion of AXO-AAV-GM2 in pediatric participants with GM2 Gangliosidosis (also known as Tay-Sachs or Sandhoff Diseases), a set of rare and fatal pediatric neurodegenerative genetic disorders caused by defects in the HEXA (leading to Tay-Sachs disease) or HEXB (leading to Sandhoff disease) genes that encode the two subunits of the β-hexosaminidase A (HexA) enzyme. AXO-AAV-GM2 is an investigational gene therapy that aims to restore HexA function by introducing a functional copy of the HEXA and HEXB genes via co-administration of two vectors utilizing the neurotropic adeno-associated virus recombinant human 8 serotype (AAVrh.8) capsid carrying the human HEXA or HEXB cDNA. The trial is expected to enroll pediatric participants with Tay-Sachs or Sandhoff Diseases, where infantile-onset participants will range from 6 months to 20 months old, and juvenile-onset participants will range from 2 years to 12 years old.

Timeline

Start

2021-01-15

Primary completion

2024-05-23

Completion

2024-12-16

Outcome

Outcome not reported

Stopped (Business): “Sponsor withdrew from the study and there was a lack of funding to complete stage 2 of the designed study.”

Publications

• Eichler F, Cataltepe OI, Daci R, Puri AS, Taghian T, Jiang X, Shazeeb MS, Kuhn A, Hader A, Celik H, Vardar Z, Lewis CJ, Artinian R, Nagy A, Vachha B, Thompson R, Gallagher T, Bateman S, Parzych J, Spanakis SG, Vaughn TA, Pier K, De Boever E, Abbott MA, D Ambrosio E, Kokoski D, Blackwood M, Drummond E, Ratai EM, Townsend EL, McLaughlin H, Tifft CJ, Keeler AM, Sena-Esteves M, Gray-Edwards HL, Flotte TR. Dual-vector rAAVrh8 gene therapy for GM2 gangliosidosis: a phase 1/2 trial. Nat Med. 2025 Sep;31(9):2927-2935. doi: 10.1038/s41591-025-03822-4. Epub 2025 Aug 15.
• De BP, Rosenberg JB, Selvan N, Wilson I, Yusufzai N, Greco A, Kaminsky SM, Heier LA, Ricart Arbona RJ, Miranda IC, Monette S, Nair A, Khanna R, Crystal RG, Sondhi D. Assessment of Safety and Biodistribution of AAVrh.10hCLN2 Following Intracisternal Administration in Nonhuman Primates for the Treatment of CLN2 Batten Disease. Hum Gene Ther. 2023 Sep;34(17-18):905-916. doi: 10.1089/hum.2023.067.

Drugs

Indications