Solid Biosciences’ Friedreich Ataxia Gene Therapy SGT-212 Garners Fast Track Designation
SGT-212, a dual route gene transfer therapy, is intended to be delivered both by intradentate nucleus infusion and IV infusion at the same time.
Solid Biosciences’ SGT-212, an adeno-associated virus (AAV) vector-based gene therapy intended to treat Friedreich ataxia (FA), has been granted fast track designation by the FDA.1
SGT-212, a dual route gene transfer therapy, is intended to be delivered both by intradentate nucleus (IDN) infusion and intravenous (IV) infusion at the same time. The therapy provides a functional copy of the disease-targeted human frataxin (FXN) gene. The IDN infusion utilizes an FDA-approved stereotactic, MRI-guided device to target the cerebellar dentate nuclei, whereas the IV infusion is intended to target cardiomyocytes. The therapy is expected to treat neurologic, cardiac, and systemic clinical manifestations of the disease. Notably, the University of Pennsylvania, Solid Biosciences, and FA212 LLC, which was founded by parents of children with FA, each contributed to the development of the investigational therapeutic.2
“SGT-212 is the only FA therapy in development that is designed to address frataxin deficiency, the underlying cause of FA, and all manifestations of this devastating disease, and in doing so, hopefully halt the full spectrum of symptom progression regardless of where the patient is in their journey with this terrible disease,” Bo Cumbo, BS, the president and chief executive officer of Solid Biosciences, said in a statement.1 “We believe fast track designation may enable us to more rapidly develop SGT-212 and bring hope to those living with FA who need and deserve better treatment options.”
Notably, the FDA recently cleared an investigational new drug (IND) application for SGT-212 on January 7, 2025. In light of the IND clearance, Solid intends to go forward with plans for a first-in-human phase 1b clinical trial (NCT identifier pending) in adults with FA. The multicenter, open-label study will include both patients who are ambulatory and patients who are nonambulatory, and will track the results for 5 years posttreatment. The company expects to dose the first patient in the second half of this year. Up to 3 cohorts will be used in the trial.2
“SGT-212 has been intentionally designed to enable highly targeted delivery of our gene therapy to both the dentate nuclei and cardiac tissue,” Cumbo said at the time of the IND clearance.2 “The IND was supported by a robust preclinical package demonstrating safe transduction and frataxin expression in these target tissues, with significant restoration of neurologic function and reversal of the cardiac implications of the disorder in mice. Over the years, we have tested several candidates using different methods of administration and have conducted multiple nonhuman primate studies, some of which extended out to a year. Based on this research, we believe a dual route of administration targeting multiple systems is the best approach in development to directly address the neurological implications that profoundly impact the everyday life of patients, while simultaneously targeting the cardiac manifestations that play a key role in more progressed disease. SGT-212 offers a truly differentiated approach to addressing FA with the potential to treat the full spectrum of symptoms, and we hope to meet each patient where they are in their FA disease course.”
In addition to SGT212, Solid is also developing SGT-003, a clinical-stage next-generation AAV vector-based gene therapy for Duchenne muscular dystrophy (DMD), and a number of candidates for cardiac indications, all of which remain in preclinical development.3 SGT-003 is currently being evaluated in the phase 1/2 INSPIRE DUCHENNE clinical trial (NCT06138639), the design of which CGTLive® recently covered in detail.4 Notably, SGT-003 uses the company’s proprietary AAV-SLB101 capsid to deliver h-µD5, a transgene encoding for a microdystrophin protein containing the R16 and R17 nNos binding protein domains. The first-in-human INSPIRE DUCHENNE study, which takes the form of an open-label, nonrandomized trial, was initiated on May 6, 2024.
