Biogen Launches Phase 3 Pediatric Trial Of Omaveloxolone For Friedreich Ataxia

Biogen Inc.June 23, 2025. It has begun dosing in the global Phase 3 BRAVE trial to test omaveloxolone (SKYCLARYS®) in children aged 2 to 16 with Friedreich ataxia (FA), a rare neurological illness. About 255 participants will be included in the randomized, double-blind experiment, which will have a 52-week treatment duration and an open-label extension. SKYCLARYS is now the only approved therapy for FA in people aged 16 and up, and it is available in more than 40 countries.

The primary endpoint of the BRAVE research is the Upright Stability Score, which is part of the modified FA rating scale and is used to assess progression in children. Global enrollment is still ongoing.

The clinical burden of Friedreich ataxia in the United States: A retrospective claims database analysis

The clinical burden of Friedreich ataxia in the United States: A retrospective claims database analysis, Perlman, Susan et al.. Journal of the Neurological Sciences, Volume 0, Issue 0, 123594. doi:10.1016/j.jns.2025.123594

 After matching, the study included 652 patients with FRDA and 3260 matched controls (mean age 33.2 years; 51.4 % females). During the follow-up period (median 26.2 months for cases and 28.3 months for controls), the incremental clinical burden in FRDA cases vs. matched controls was high: patients with FRDA had significantly higher odds of loss of ambulation (odds ratio: 158.0 [95 % confidence interval (CI): 112.4–222.3]), cardiomyopathy (59.2 [41.6–84.1]), scoliosis (49.0 [35.4–67.9]), falls (7.4 [5.9–9.2]), diabetes (2.5 [2.0–3.2]), head injury (2.4 [1.9–3.0]), and fracture (3.3 [2.6–4.2]) compared to controls (all p < 0.001). Patients with FRDA also experienced a higher risk of mortality than controls (hazard ratio: 3.9 [95 % CI: 2.4–6.4]).

Stable Isotope Labeling in Bacteria Enables Characterization and Quantification of Frataxin Protein in a Friedreich’s Ataxia Zebrafish Model

Stable Isotope Labeling in Bacteria Enables Characterization and Quantification of Frataxin Protein in a Friedreich’s Ataxia Zebrafish Model, Teerapat Rojsajjakul, Wonwook Do, Robert B. Wilson, and Ian A. Blair Analytical Chemistry Article ASAP DOI: 10.1021/acs.analchem.4c07095

We developed an alternative strategy involving the use of a stable isotope-labeled internal standard coupled with analysis by high-sensitivity ultrahigh-performance liquid chromatography-multiple reaction monitoring-mass spectrometry (UHPLC-MRM/MS). UHPLC-MRM/MS with a SILIB internal standard was the only way to validate zebrafish heterozygous for a knockout mutation in zFXN as a model for FRDA, illustrating its utility for the characterization and quantification of very low abundance tissue proteins.

Pharmacokinetics and Pharmacodynamics of Nomlabofusp in Non-clinical Studies of Friedreich's Ataxia

De Toni F, Ragaglia V, Schecter D, Miller AS, Gonzalez E, Wagner EJ, Xu X, Payne RM, Mess JN, Baile MG, Clements-Egan A, Shankar G. Pharmacokinetics and Pharmacodynamics of Nomlabofusp in Non-clinical Studies of Friedreich's Ataxia. AAPS J. 2025 Jun 25;27(5):112. doi: 10.1208/s12248-025-01093-y. PMID: 40562976. 

We demonstrate that subcutaneous administration of nomlabofusp distributes in a dose-dependent manner to several organs including the dorsal root ganglion, heart, and skeletal muscle, which are known to be predominantly affected in Friedreich's ataxia, as well as to other tissues, including skin. Plasma nomlabofusp concentrations correlated with levels of human frataxin delivered by nomlabofusp into tissues, and the increases in frataxin were correlated amongst tissues, especially with skin. In the knockout mice, we show that the pharmacokinetics and processing of nomlabofusp were comparable with wild type animals and that treatment with nomlabofusp halts the progression of cardiac dysfunction and significantly increased survival. Together, the findings from these non-clinical studies demonstrate that nomlabofusp exposure increases human frataxin in Friedreich's ataxia-relevant tissues and provide evidence of pharmacologic effects.

Larimar Therapeutics Announces FDA Recommendations on Safety Database, and Other Details of Nomlabofusp BLA Submission for Friedreich’s Ataxia Program

BALA CYNWYD, Pa., June 23, 2025 (GLOBE NEWSWIRE) -- Larimar Therapeutics, Inc. (Larimar) (Nasdaq: LRMR), a clinical-stage biotechnology company focused on developing treatments for complex rare diseases, today announced FDA safety database recommendations and refined timeline for Biologics License Application (BLA) submission to allow for the inclusion of the recommended safety data from adults and children with Friedreich’s Ataxia (FA). This comes following written responses from the U.S. Food and Drug Administration (FDA) based on discussions under the Support for Clinical Trials Advancing Rare Disease Therapeutics (START) pilot program.