Larimar Therapeutics, Inc. (LRMR) has announced encouraging initial data from its long-term open label extension (OLE) study of nomlabofusp in participants with Friedreich's Ataxia (FA). The OLE study data indicates that nomlabofusp treatment leads to increased frataxin (FXN) levels in patients, addressing the frataxin deficiency that characterizes FA. These findings support the potential of nomlabofusp to slow the progression of this debilitating neurodegenerative disorder.
Nomlabofusp Increases Frataxin Levels
Friedreich's ataxia, a genetic and progressive neurodegenerative disease, results from GAA repeats in the FXN gene, leading to FXN deficiency. Data from the OLE study demonstrated that nomlabofusp raised frataxin levels in participants. According to Larimar, increasing frataxin levels may slow the disease's progression. In the OLE study, 25 mg of nomlabofusp administered daily increased and maintained tissue FXN levels over time, with mean levels increasing from 15% of healthy volunteers at baseline to 30% in buccal cells and from 16% to 72% in skin cells at Day 90.
Pediatric Studies Underway
Larimar has also begun dosing adolescents aged 12-17 in a pediatric pharmacokinetic (PK) run-in study. Adolescents receive a weight-based dose equivalent to the 50 mg adult dose. Following assessment of safety and PK data of each successive cohort, participants will be eligible to screen for the OLE study. A cohort of children (2- 11 years old) is planned to initiate in the first half of 2025.
Modeling and Simulation Data
Data presented at the International Congress for Ataxia Research (ICAR) included modeling and simulation predicting that daily administration of 50 mg nomlabofusp is likely to achieve skin FXN levels > 50% of healthy controls in most patients, similar to mean tissue FXN levels observed in asymptomatic heterozygous carriers. Furthermore, gene expression and lipid profiles in study participants with FA were observed to improve directionally towards values seen in healthy controls, suggesting that nomlabofusp has the potential to affect downstream metabolic pathways that may be disrupted in patients with FA.
Path to Potential Registration
Larimar Therapeutics is moving forward with plans to initiate a registrational study of nomlabofusp in mid-2025 and intends to submit a Biologics License Application (BLA) in the second half of 2025. The long-term safety, PK, and FXN data collected in the OLE study are intended to support a potential accelerated approval using FXN as a novel surrogate endpoint. The company is also advancing discussions with the FDA on the data package required to support accelerated approval, including supplementary nonclinical pharmacology investigations, and FXN, supportive PD, and safety and clinical outcomes data from the OLE study.
According to Dr. Susan Perlman, Professor of Neurology and Director of the Ataxia Center, David Geffen School of Medicine at UCLA, “Friedreich’s ataxia is caused by frataxin deficiency, and disease progression is more rapid in patients with lower frataxin levels. Increases in frataxin levels in patients with FA may lead to the slowing of progression.”
