The Food and Drug Administration (FDA) has cleared the investigational new drug (IND) application to initiate a registrational study of adeno-associated viral (AAV) vector gene therapy (AXO-AAV-GM2; Axovant Gene Therapies, New York, NY) to treat individuals with Tay-Sachs disease and Sandhoff disease. This therapy, if effective, will produce the enzyme beta-hexosaminidase A and B, deficiencies of which are causative for Tay Sachs syndrome and Sandhoff disease. It is hoped to be curative for both illnesses, which are lysosomal storage disorders, typically fatal in childhood.
AXO-AAV-GM2 delivers 2 vectors encoding the HEXA and HEXB genes directly to the central nervous system to produce a fully functional β-Hexosaminidase A enzyme. In 2019, clinical evidence from 2 participants under an investigator-initiated study found that treatment with the gene therapy was generally well-tolerated and associated with improved bioactivity outcomes. In addition, the data demonstrated the attainment of normal neurodevelopmental milestones and improvement in myelination. The gene therapy has been granted Orphan Drug and Rare Pediatric Disease Designation by the FDA.
Axovant aims to advance the program through strategic partnerships with leading research organizations. The Company recently announced a partnership with Viralgen, an AskBio subsidiary, to support AAV-based vector manufacturing of clinical trial material for the registrational study. Additionally, through an existing genetic testing collaboration with Invitae, ongoing partnership with GM2 gangliosidosis patient groups, and collaboration with leading academic researchers at the University of Massachusetts Medical School and Massachusetts General Hospital, Axovant expects to begin participant identification and site startup activities in preparation for dosing children in the planned clinical study.
The study will enroll both infantile and juvenile participants with GM2 gangliosidosis in the US The 2-part trial, sponsored by Axovant, will consist of a dose ranging cohort evaluating the safe and efficacious dose of the gene therapy, followed by an efficacy cohort, both of which form the basis of the registrational program. Terence R. Flotte, MD, professor of Pediatrics and dean at the University of Massachusetts Medical School, will serve as principal investigator on the clinical trial.
Nupur Ghoshal, MD, PhD
Adam M. Staffaroni, PhD; Elena Tsoy, PhD; Jack Taylor, BS; Adam L. Boxer, MD, PhD; and Katherine L. Possin, PhD
Cyrus A. Raji, MD, PhD; Somayeh Meysami, MD; and Mario F. Mendez, MD, PhD