SGT-212 (formerly FA-212) is a gene addition therapy with dual delivery to both the heart and the dentate nucleus of the brain using an AAV9 variant for delivery.
FA is a candidate for genetic therapy because it is caused by a mutation in a single gene, FXN. Mutations in FXN cause low production of a protein called frataxin, which leads to the symptoms of FA. Genetic therapies are treatment approaches that aim to address a disease at the DNA level. Gene addition is one type of genetic therapy that is designed to deliver working copies of the FXN gene to cells within the body. These delivered FXN genes would then produce frataxin protein.
The drug development process can be thought of as a series of stages, and successful drugs must pass through each stage to become available to patients.
SGT-212 is a recombinant AAV-based gene addition therapy for Friedreich’s ataxia (FA) designed to deliver the full-length human frataxin gene (FXN) via a dual route of administration: intradentate nucleus (IDN) infusion, using an MRI-guided device, followed by an intravenous (IV) infusion to increase therapeutic frataxin levels in the cerebellar dentate nuclei and in the cardiomyocytes, respectively. Restoration of frataxin protein levels is expected to repair the underlying mitochondrial dysfunction in neurons and cardiomyocytes to address both neurologic and cardiac manifestations of the disease. In mouse models, SGT-212 shows efficacious transduction of the heart and the dentate nucleus at low doses that avoid DRG toxicity.
This program originated with FA212 LLC, a company founded by FA families, led by Tom Hamilton. The program was purchased by Solid Biosciences and will be further developed by that company. In a letter to the FA community, Solid shared that the development of SGT-212 (previously FA-212) would not have been possible without the previous efforts of the LLC. “…Additionally, the Friedreich’s Ataxia Research Alliance (FARA), the University of Pennsylvania, and most importantly, the FA patient community all contributed to the development of this program. The insights and feedback shared by individuals and families living with FA have been instrumental in shaping this program, ensuring that it reflects the real hopes and needs of the community. Your resilience and determination inspire us every day, and we are honored to bring SGT-212 to patients.”
January 7, 2025: Solid Biosciences announced that the U.S. Food and Drug Administration (FDA) cleared its Investigational New Drug (IND) application for SGT-212 for the treatment of Friedreich’s ataxia (FA), a degenerative disease caused by insufficient levels of the frataxin protein. SGT-212 is the Company’s novel, AAV-based FA gene therapy candidate designed to deliver full-length frataxin via systemic intravenous (IV) infusion as well as direct intradentate nuclei (IDN) infusion into the cerebellum. SGT-212 is designed to treat the neurologic and systemic clinical manifestations of FA to address the full spectrum of disease progression. SGT-212 was developed by FA212 LLC, a company founded by parents of children living with FA, the University of Pennsylvania, and Solid Biosciences. Solid Biosciences stated that it expects to initiate a first-in-human, open-label, dose-finding Phase 1b clinical trial of SGT-212 in the second half of 2025. The study will enroll non-ambulatory and ambulatory adult patients living with FA across up to three cohorts and will evaluate the safety and tolerability of contemporaneous systemic and bilateral IDN administration of SGT-212. Participants in the trial will be followed out to five years after receiving SGT-212.
Read the letter from Solid BioSciences to the FA community about this first regulatory filing.
January 21, 2025: Solid Biosciences announced that it has received Fast Track designation from the U.S. Food and Drug Administration (FDA) for SGT-212, the Company’s, AAV-based gene therapy candidate for the treatment of Friedreich’s ataxia (FA).
This brief video serves as an introduction to gene therapy for FA. The aim of this video and accompanying educational resources is to provide information to help individuals and families make informed decisions regarding participation in clinical trials exploring investigational drugs or gene therapy.
