Lexeo Therapeutics Announces FDA Breakthrough Therapy Designation for LX2006 in Friedreich Ataxia

07/07/2025 ;Lexeo Therapeutics (Nasdaq: LXEO) has achieved a significant milestone as its drug candidate LX2006 received FDA Breakthrough Therapy designation for treating Friedreich ataxia (FA). The designation was based on promising interim clinical data from Phase I/II trials showing meaningful improvements in cardiac biomarkers and functional measures. The drug has demonstrated clinically significant improvements in cardiac and neurologic functional measures, with increased frataxin expression observed in all cardiac biopsy participants at three months post-treatment. To date, 17 participants have been treated across two trials. The company plans to initiate a registrational study by early 2026. Additionally, LX2006 has been selected for the FDA's Chemistry, Manufacturing, and Controls Development and Readiness Pilot (CDRP) program, aimed at facilitating faster patient access to promising therapies.

Antisense oligonucleotide therapy for Friedreich’s ataxia patients carrying the c.165+5G>C splicing mutation

Antisense oligonucleotide therapy for Friedreich’s ataxia patients carrying the c.165+5G>C splicing mutation. Yameogo, Pouiré et al. Molecular Therapy Nucleic Acids, Volume 0, Issue 0, 102617. DOI:10.1016/j.omtn.2025.102617

This ASO strategy may be therapeutically feasible for FRDA patients with other point mutations that cause splicing defects. Success in developing treatments for disorders with only a few known cases will give hope to FRDA patients carrying these rare point mutations.

Antisense oligonucleotide therapy for Friedreich’s ataxia patients carrying the c.165+5G>C splicing mutation

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.

Biogen Disappointed by INESSS Recommendation on SKYCLARYS™ and its Impact on Quebec Patients with Friedreich Ataxia

TORONTO, June 5, 2025 /CNW/ - Biogen Canada Inc. is disappointed by INESSS's recommendation against listing SKYCLARYS™ (omaveloxolone), despite its therapeutic potential for individuals living with Friedreich ataxia (FA) — a community in urgent need of treatment options.

Autosomal Recessive Cerebellar Ataxias: Translating Genes to Therapies

Fogel, B.L., Klopstock, T., Lynch, D.R., Maltecca, F., Verma, M., Minassian, B.A., Platt, F.M., Gonçalves, D.F., Puccio, H., Roos, A. and Synofzik, M. (2025), Autosomal Recessive Cerebellar Ataxias: Translating Genes to Therapies. Ann Neurol. doi:10.1002/ana.27271 

 Autosomal recessive cerebellar ataxias (ARCAs) represent over 200 clinically heterogeneous genetic conditions involving degeneration of the cerebellum and associated tracts with resultant impairment of balance and coordination. Advancements in genomic testing have enabled rapid identification of the majority of known recessive disorders, shifting research focus to the development of targeted mechanistic treatments addressing underlying physiological pathways. Molecular classification allows recognition of cellular, biochemical, and genetic targets for high-effect precision therapy development. ARCAs represent a significant global health burden, requiring establishment of a robust pathway for novel therapeutic discovery through modification of mechanisms of disease pathogenesis and subsequent clinical trial development.

Health-related quality of life and productivity burden for non-professional caregivers of adults with rare diseases: a real-world study

Johnson, B., Gibson, G., Baskerville, D. et al. Health-related quality of life and productivity burden for non-professional caregivers of adults with rare diseases: a real-world study. Orphanet J Rare Dis 20, 282 (2025). doi:10.1186/s13023-025-03796-z 

The substantial burden of providing non-professional caregiving to adults with rare diseases is associated with multiple factors. Interventions improving care recipient HRQoL could enhance caregiver HRQoL and productivity.