FDA Clears IND for Trial Assessing Gene Therapy SGT-212 in Friedreich Ataxia

Bo Cumbo, president and chief executive officer at Solid

The FDA has given clearance to Solid Biosciences’ investigational new drug application (IND) for SGT-212, an adeno-associated virus (AAV)-based gene therapy candidate for Friedreich ataxia (FA). A phase 1b, first-in-human, open-label, dose-finding trial featuring non-ambulatory and ambulatory adults with FA is expected to begin the second half of 2025.¹

SGT-212 is designed to deliver full-length human frataxin (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 Fxn levels in the cerebellar dentate nuclei and in the cardiomyocytes, respectively. A unique agent, SGT-212 is geared towards treating both the neurologic and systemic clinical manifestations of FA to address the full spectrum of disease progression.

"SGT-212 has been intentionally designed to enable highly targeted delivery of our gene therapy to both the dentate nuclei and cardiac tissue," Bo Cumbo, president and chief executive officer at Solid, said in a statement.¹ "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."

He added, "Over the years, we have tested several candidates using different methods of administration and have conducted multiple NHP 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."

The proposed phase 1b study will enroll patients across up to 3 cohorts, testing the safety and tolerability of contemporaneous systemic and bilateral IDN administration of SGT-212. In the study, patients will be followed out to 5 years after receiving the gene therapy candidate.

READ MORE: Expanding the Clinical Care of Friedreich Ataxia Through Omaveloxlone and SKYCLARYS PASS Registry

"Gene therapy approaches are aimed at the underlying causes of FA, and thus important in the overall strategy to treat and cure this disease. There has been encouraging progress in the FA treatment landscape; however, there is still unmet medical need for our patient community. Through our work with individuals living with FA and their families, we know they seek therapies designed to treat the debilitating neurologic symptoms that people living with FA face day-to-day, such as loss of ambulation and coordination, dysarthria, along with the life-shortening cardiac disease," Jennifer Farmer, chief executive officer at the Friedreich’s Ataxia Research Alliance, said in a statement.¹

Solid Bioscience, a precision genetic medicine company, has several other gene therapy candidates in the pipeline, including SGT-003 for Duchenne muscular dystrophy (DMD), SGT-501 for catecholaminergic polymorphic ventricular tachycardia, SGT-601 for TNNT2-mediated dilated cardiomyopathy, and SGT-401 for BAG3-mediated dilated cardiomyopathy. SGT-003, its most advanced agent, is being tested in a phase 1/2 trial, dubbed INSPIRE Duchenne, which serves as a first-in-human, open-label, multicenter study featuring 2 cohorts of patients with DMD.

In 2022, the company announced a pause on development for SGT-001, its previous lead candidate for DMD, in favor of SGT-003.² Prior to the reprioritization, Solid had presented positive 2-year data from the phase 1/2 IGNITE-DMD trial (NCT03368742) at the 2022 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference, held March 13-16, in Nashville, Tennessee, assessing SGT-001. These data, which included the first 3 patients treated in the high-dose cohort (2E¹⁴vg/kg), were in line with previous data reported from the 12- and 18-month time points.³

In IGNITE-DMD, patients treated with SGT-003 demonstrated motor function improvements, including a 16-meter gain in the 6-Minute Walk Test (range: -12 to 39; +100.6 vs. natural history) and a -1.7 change in the North Star Ambulatory Assessment (range: -3 to -1; +4.3 vs. natural history). Pulmonary function also improved, with a 9.2% increase in forced vital capacity (range: -1.4 to 29.0; +19.2 vs. natural history) and a 6.5% rise in peak expiratory flow (range: -5.8 to 14.8; +16.5 vs. natural history). Additionally, patient-reported outcomes showed improvement, and the therapy was well-tolerated.

REFERENCES
1. Solid Biosciences Announces FDA IND Clearance for First-In-Industry Dual Route of Administration Gene Therapy to Treat Both Neurologic and Cardiac Manifestations of Friedreich’s Ataxia. News release. Solid Biosciences. January 7, 2025. Accessed January 8, 2025. https://www.globenewswire.com/news-release/2025/01/07/3005854/0/en/Solid-Biosciences-Announces-FDA-IND-Clearance-for-First-In-Industry-Dual-Route-of-Administration-Gene-Therapy-to-Treat-Both-Neurologic-and-Cardiac-Manifestations-of-Friedreich-s-At.html
2. Solid Biosciences provides second quarter 2022 business update and financial results. News release. Solid Biosciences. August 11, 2022. Accessed January 8, 2025. https://www.solidbio.com/about/media/press-releases/solid-biosciences-provides-second-quarter-2022-business-update-and-financial-results
3. Dreghici R, Redican S, Lawrence J, et al. Ignite DMD phase I/II study of SGT-001 microdystrophin gene therapy for DMD: 2-year outcomes update. Presented at MDA Clinical and Scientific Conference; March 13-16. Poster 46.