Larimar Therapeutics Provides Nomlabofusp Development Update and Reports Fourth Quarter and Full Year 2024 Financial Results

BALA CYNWYD, Pa., March 24, 2025 (GLOBE NEWSWIRE) -- Larimar Therapeutics, Inc. (Larimar) Potential for Accelerated Approval Pathway Based on FXN Concentrations as a Reasonably Likely Surrogate Endpoint (RSLE): FDA stated in written correspondence associated with a meeting through the START pilot program that they are open to considering the use of FXN concentration as a RLSE and the acceptability of FXN’s use as an RLSE would ultimately be a matter of review of the data in a future marketing application.

Increases in Skin FXN as Evidence of Effectiveness: FDA recommended focusing on assessments of skin FXN concentrations rather than buccal FXN concentrations due to more consistent sampling and less variability. FDA acknowledged that recently submitted data appear to support a relationship between increased FXN concentrations in skin cells and relevant tissues such as the heart, dorsal root ganglion and skeletal muscle. FDA also acknowledged that the nonclinical studies were performed at relevant human doses.

FDA also suggested that Larimar consider exploring the relationship between increases in FXN in skin and changes in pharmacodynamic markers such as lipid profiles and/or clinical measures to provide additional support for the use of FXN as a RLSE.

BLA Submission and Initiation of Global Phase 3 Study on Track: Larimar has obtained feedback from both FDA and EMA on the global Phase 3 study protocol and is on track to initiate the study by mid-2025 with potential sites in the U.S., Europe, U.K., Canada, and Australia. Larimar is targeting the BLA submission to seek accelerated approval by the end of 2025.

Comparative analysis of large language models on rare disease identification

Ao, G., Chen, M., Li, J. et al. Comparative analysis of large language models on rare disease identification. Orphanet J Rare Dis 20, 150 (2025). doi:10.1186/s13023-025-03656-w 

The LLMs performed better than human physicians, and Claude 3.5 Sonnet achieved the highest accuracy at 78.9%, significantly surpassing the accuracy of human physicians, which was 26.3%. These findings suggest that LLMs can improve rare disease diagnosis and serve as valuable tools in clinical settings, particularly in regions with limited resources. However, further validation and careful consideration of ethical and privacy issues are necessary for their effective integration into medical practice.

Early onset development of hypertrophic cardiomyopathy in less than 1 year in a patient with familial Friedrich's ataxia: Case report

Yasmine Ouaddouh, Salma Bouyaddid, Zakaria Bazid, Nabila Ismaili, Noha El Ouafi, Early onset development of hypertrophic cardiomyopathy in less than 1 year in a patient with familial Friedrich's ataxia: Case report, Radiology Case Reports, Volume 20, Issue 6, 2025, Pages 3016-3020, ISSN 1930-0433, doi:10.1016/j.radcr.2025.03.001. 

Friedreich's hypertrophic cardiomyopathy has been reported as the most significant cause of mortality, especially among younger patients with early onset disease manifestations.

Jupiter Neurosciences Inc. (JUNS) reports earnings

The report was filed on March 28, 2025. JOTROL is being developed for multiple indications including Parkinson’s Disease, Mild Cognitive Impairment/early Alzheimer’s Disease, and rare diseases such as Mucopolysaccharidoses Type 1, Friedreich’s ataxia, and MELAS.

Redox homeostasis and Inflammation in fibroblasts of patients with Friedreich Ataxia: a possible cross talk

Andrea Quatrana, Sara Petrillo Sara Petrillo, Caterina Torda Caterina Torda, Eleonora De Santis, Enrico Bertini Enrico Bertini, Fiorella Piemonte. Front. Mol. Neurosci., Sec. Molecular Signalling and Pathways, Volume 18 - 2025 | doi: 10.3389/fnmol.2025.1571402.

We found a significant activation of the TLR4/NF-kB/IL-1β axis in patients, associated to a consistent increase of the redox enzymes thioredoxin 1 (TRX1) and glutaredoxin 1 (GLRX1), which are essential to activate NF-kB under oxidative stress conditions. Furthermore, we investigated the role of 4-HNE, a by-product of lipid peroxidation, as a potential mediator between ferroptosis and inflammation in FRDA.

Systemic AAV Gene Therapy with Next Generation Engineered Capsids for Treatment of CNS and Cardiac Symptoms in Friedreich’s Ataxia

MDA Conference 2025. Ryan Kast, PhD, Capsida Biotherapeutics, Celeste Stephany, PhD, Capsida Biotherapeutics, Miguel Chuapoco, PhD, Capsida Biotherapeutics, Xiaojing Shi, PhD, Capsida Biotherapeutics, Assaf Beck, PhD, Capsida Biotherapeutics, Austin Kidder, Capsida Biotherapeutics, Yixi Wang, Capsida Biotherapeutics, Kevin Lam, Capsida Biotherapeutics, Nicholas Flytzanis, PhD, Capsida Biotherapeutics, Nick Goeden, PhD, Capsida Biotherapeutics. The engineered capsid delivering human FXN transduced more than 80% of cerebellar Purkinje cells, dentate nucleus neurons, motor neurons in the cortex and spinal cord, and nearly 30% of cardiac tissue area. FXN protein levels in treated NHPs were 8.2x higher than endogenous levels in the motor cortex and 1.7x in the heart as measured by ELISA. Moreover, substantial FXN RNA expression was detected in the retina (~1E6 copies/ug RNA) suggesting potential benefit for sensory vision loss experienced by FA patients. Significant de-targeting of the liver and other non-target tissues contributed to the favorable safety profile characterized by no adverse immunogenicity, clinical pathology, and histopathology findings.

LEXEO THERAPEUTICS REPORTS FOURTH QUARTER AND FULL YEAR 2024 FINANCIAL RESULTS AND OPERATIONAL HIGHLIGHTS

NEW YORK, March 24, 2025 (GLOBE NEWSWIRE) -- Lexeo Therapeutics, Inc. . 

Mid-Year Clinical Update Expected to Include: 

Safety and tolerability data for all participants dosed across both the SUNRISE-FA and Weill Cornell clinical trials (at least 16 participants, including 6 participants with abnormal LVMI at baseline) 

Pre- and post-treatment cardiac frataxin protein expression measured via LCMS for all four participants at the highest dose (1.2x1012 vg/kg, Cohort 3) 

Clinical biomarker data, including left ventricular mass index (LVMI), left ventricular wall thickness and high-sensitivity troponin I, for participants with >6-months of follow up 

Functional and patient-reported outcome data for participants with >6-months of follow up 

Safety: LX2006 continues to be generally well tolerated with no new treatment-related serious adverse events to report

Neuroimaging Biomarkers for Friedreich Ataxia: A Cross-Sectional Analysis of the TRACK-FA Study

Georgiou-Karistianis, N., Corben, L.A., Lock, E.F., Bujalka, H., Adanyeguh, I., Corti, M., Deelchand, D.K., Delatycki, M.B., Dogan, I., Farmer, J., França, M.C., Jr., Gabay, A.S., Gaetz, W., Harding, I.H., Joers, J., Lax, M.A., Li, J., Lynch, D.R., Mareci, T.H., Martinez, A.R.M., Pandolfo, M., Papoutsi, M., Parker, R.G., Reetz, K., Rezende, T.J.R., Roberts, T.P., Romanzetti, S., Rudko, D.A., Saha, S., Schulz, J.B., Subramony, S.H., Supramaniam, V.G., Lenglet, C. and Henry, P.-G. (2025), Neuroimaging Biomarkers for Friedreich Ataxia: A Cross-Sectional Analysis of the TRACK-FA Study. Ann Neurol. doi: 10.1002/ana.27237

 Our findings provide strong imaging evidence of impaired development of spinal cord and superior cerebellar peduncles during childhood in Friedreich ataxia and open the way for the use of neuroimaging biomarkers in clinical trials.

Debates over orphan drug pricing: a meta-narrative literature review

Hanchard, M.S. Debates over orphan drug pricing: a meta-narrative literature review. Orphanet J Rare Dis 20, 107 (2025). doi:10.1186/s13023-025-03634-2 

The review finds a sustained call for reform, centred on welfare economics and resource allocation, where current incentives and regulations are held to be insufficient. Overall, the article recommends that regulators look to alternative models of innovation steeped in social science thinking to modify reviewing appraisal, coverage, and reimbursement processes for orphan drugs. Also, that greater patient inclusion and transparency would help include a wider range of intangible social factors that rare disease patients face in accessing high priced orphan drugs.

Brain microvascular endothelial cells differentiated from a Friedreich's Ataxia patient iPSC are deficient in tight junction protein expression and paracellularly permeable

Brain microvascular endothelial cells differentiated from a Friedreich's Ataxia patient iPSC are deficient in tight junction protein expression and paracellularly permeable. Front. Mol. Neurosci. Sec. Brain Disease Mechanisms, Volume 18 - 2025 | doi: 10.3389/fnmol.2025.1511388 

These data show that decreased barrier integrity is a pathophysiologic phenotype of FA brain microvascular endothelial cells. Clinically, this may be a targetable pathway to abrogate brain iron accumulation, neuroinflammation, and neurodegeneration profiles of FA. Additionally, investigation into other barrier systems, such as the blood-nerve barrier, blood-CSF barrier, or cardiac vasculature may inform on extra-neural symptoms experienced by the FA patient.