FDA Action Update, February 2025: Approvals, Designations, and Acceptances

NeurologyLive. March 9, 2025. The FDA was busy in March 2025, making a number of decisions on potential new therapeutic agents including granting approvals, acceptances, and designations.

- Solid Biosciences' SGT-212 gene therapy for Friedreich ataxia received FDA clearance, targeting neurologic and systemic manifestations via dual administration routes. 

-On the same day, February 19, the FDA accepted PTC Therapeutics’ new drug application (NDA) for its investigational agent vatiquinone as a treatment for patients with Friedreich ataxia (FA)

Robust behavioral assessment of the inducible Friedreich's ataxia mouse does not show improvement with NRF2 induction

Claire B. Montgomery, Lili Salinas, Garrett P. Cox, Lauren E. Adcock, Tiffany Chang, Francisco Figueroa, Gino Cortopassi, Elena N. Dedkova; Robust behavioral assessment of the inducible Friedreich's ataxia mouse does not show improvement with NRF2 induction. Dis Model Mech 2025; dmm.052128. doi: https://doi.org/10.1242/dmm.052128

 We developed a novel Salinas-Montgomery Ataxia Scale (SMAS) which allows for more comprehensive assessment versus a 4-part cerebellar ataxia scale. Despite validating multiple sensitive techniques, we did not see any benefits of NRF2-inducing therapies in any tests. This was exacerbated by the discovery of a sexual dimorphism in FXNKD mice, in which males show a more significant decline and better responsiveness to NRF2-inducing therapeutics.

Solid Biosciences Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Updates

CHARLESTOWN, Mass., March 06, 2025 (GLOBE NEWSWIRE) -- Solid Biosciences Inc. SGT-212 for Friedreich’s ataxia (FA) As announced on January 7, 2025, the FDA has cleared the IND for SGT-212 for the treatment of FA. SGT-212 is the first gene therapy candidate to utilize a dual route of administration to treat FA. The Company expects to initiate a first-in-human, open-label, Phase 1b clinical trial of SGT-212 in the second half of 2025. The trial is expected to enroll non-ambulatory and ambulatory adult participants living with FA across up to three cohorts and is designed to evaluate the safety and tolerability of concurrent systemic and bilateral IDN administration of SGT-212.

Gait Characteristics in People with Friedreich Ataxia: Daily Life versus Clinic Measures

Hannah L. Casey • Vrutangkumar V. Shah • Daniel Muzyka • James McNames • Mahmoud El-Gohary • Kristen Sowalsky • Delaram Safarpour • Patricia (Patty) Carlson-Kuhta • Christian Rummey • Fay B. Horak • Christopher M. Gomez, Front. Neurol. Sec. Movement Disorders, Volume 16 - 2025 | doi: 10.3389/fneur.2025.1544453 

Digital gait characteristics from inertial sensors are sensitive and specific for FRDA in both environments. However, different gait measures were more sensitive and specific during free-living versus prescribed gait, suggesting that in-clinic gait does not reflect daily life gait.

A global perspective on research advances and future challenges in Friedreich ataxia

Indelicato, E., Delatycki, M.B., Farmer, J. et al. A global perspective on research advances and future challenges in Friedreich ataxia. Nat Rev Neurol (2025). doi:10.1038/s41582-025-01065-y

Nrf2 activators for the treatment of rare iron overload diseases: From bench to bedside

Dong Y, Zheng M, Ding W, Guan H, Xiao J, Li F. Nrf2 activators for the treatment of rare iron overload diseases: From bench to bedside. Redox Biol. 2025 Feb 14;81:103551. doi: 10.1016/j.redox.2025.103551. Epub ahead of print. PMID: 39965404.

 Despite these uses, the therapeutic potentials of Nrf2 activators for iron overload disorders may be overlooked in clinical practice. Therefore, this study talks about the potential use, possible mechanisms, and precautions of Nrf2 activators in treating rare iron overload diseases.

Effect of a Supratherapeutic Dose of Omaveloxolone on the Corrected QT Interval in Healthy Participants: A Randomized, Double-Blind, Placebo- and Active-Controlled, Three-Way Crossover Study

Zahir H, Murai M, Wu L, Valentine M, Hynes SM. Effect of a Supratherapeutic Dose of Omaveloxolone on the Corrected QT Interval in Healthy Participants: A Randomized, Double-Blind, Placebo- and Active-Controlled, Three-Way Crossover Study. Clin Transl Sci. 2025 Feb;18(2):e70139. doi: 10.1111/cts.70139. PMID: 39976332; PMCID: PMC11840845. 

No safety concerns were identified. Supratherapeutic omaveloxolone exposure that covers the worst-case clinical exposure did not cause a clinically significant QTc prolongation and was generally well tolerated.

Multiple Sclerosis in a Patient with Friedreich's Ataxia

Yu Y, Kushlaf H. Multiple Sclerosis in a Patient with Friedreich's Ataxia (P4-6.016). Neurology. 2024 Apr 9;102(7_supplement_1):3347. doi: 10.1212/WNL.0000000000205077. Epub 2024 Apr 9. PMID: 39977947. 

The definitive diagnosis of multiple sclerosis in a FRDA patient is novel and requires careful reconciliation of the symptoms, clinical exam findings, and ancillary testing. The development of symptoms incompatible with FRDA should prompt clinicians to consider additional neurologic diagnoses.

Healthcare delay in neurogenetic disorders of adult onset and the role of predictive genetic testing

Rocha, D.L., Pinheiro, J.d., Furtado, G.V. et al. Healthcare delay in neurogenetic disorders of adult onset and the role of predictive genetic testing. J Community Genet (2025). doi:10.1007/s12687-025-00777-4 

Healthcare delay (HCDe) is an important but not well-known issue in genetic disorders, especially in tandem nucleotide repeat expansion diseases (TNRED). We aimed to investigate it and determine whether predictive genetic testing (PGT) and other factors may impact HCDe.

Frataxin deficiency and the pathology of Friedreich's Ataxia across tissues

Ercanbrack WS, Ramirez M, Dungan A, Gaul E, Ercanbrack SJ, Wingert RA. Frataxin deficiency and the pathology of Friedreich's Ataxia across tissues. Tissue Barriers. 2025 Feb 21:2462357. doi: 10.1080/21688370.2025.2462357. Epub ahead of print. PMID: 39981684. 

Most FRDA patients suffer from loss of motor control, cardiomyopathy, scoliosis, foot deformities, and diabetes. In this review, we discuss the known features of FRDA pathology and the current understanding about the basis of these alterations.