Larimar Therapeutics, Inc. (Nasdaq: LRMR), a clinical-stage biotechnology company headquartered in Bala Cynwyd, Pennsylvania, announced receipt of US FDA Breakthrough Therapy Designation (BTD) for nomlabofusp, a recombinant frataxin (FXN) protein replacement therapy, for the treatment of adults and children with Friedreich’s ataxia (FA). The designation, coupled with alignment from a recent FDA meeting on the use of skin frataxin as a surrogate endpoint, positions Larimar to submit a Biologics License Application (BLA) seeking accelerated approval in June 2026, with a US launch targeted for the first half of 2027.
BTD status is reserved for drugs intended to treat a serious condition where preliminary clinical evidence indicates potential to produce substantial improvement over available treatments on one or more clinically relevant endpoints. The designation carries all procedural benefits of Fast Track Designation — including eligibility for Rolling Review and Priority Review, as well as more frequent meetings and written communication with the FDA — and adds intensive guidance on efficient drug development, along with organizational commitment involving senior FDA managers.
Larimar already holds Fast Track Designation, Orphan Drug Designation, and Rare Pediatric Disease Designation for nomlabofusp. The BTD adds a layer of FDA engagement that could prove relevant as the agency evaluates the adequacy of the safety database and the use of a surrogate endpoint — skin FXN levels — that has not previously served as a basis for approval in any disease.
Nomlabofusp in Friedreich ataxia
The BTD was granted on the basis of preliminary clinical data from Larimar’s ongoing open-label (OL) study evaluating nomlabofusp in adult and pediatric patients with FA. Data submitted to the FDA showed nomlabofusp increased skin frataxin to levels expected in asymptomatic carriers of the FXN gene expansion — individuals who carry one mutated allele but do not develop disease. Across four clinical outcome measures assessed after one year of treatment — modified Friedreich Ataxia Rating Scale (mFARS), FARS-Activities of Daily Living (ADL), 9-Hole Peg Test (9-HPT), and Modified Fatigue Impact Scale (MFIS) — the company reported consistent directional improvement relative to a matched reference group drawn from the Friedreich’s Ataxia Clinical Outcomes Measure Study (FACOMS) natural history database.
The open-label study design, lacking a concurrent placebo arm, is a limitation that the company and the FDA appear to be managing through exposure-response analyses and the natural history comparator. The FDA confirmed during a recent Support for Clinical Trials Advancing Rare Disease Therapeutics (START) pilot program meeting that the proposed statistical approach — linking nomlabofusp exposure to clinical outcomes and comparing treated patients against FACOMS-matched controls — is the type of analysis that could support a BLA submission. The agency also offered to provide advance review and comment on the statistical plan, a degree of proactive engagement consistent with the BTD framework.
Topline data from the open-label study to support the Larimar Therapeutics nomlabofusp BLA are expected in Q2 2026. Separately, a pediatric pharmacokinetic run-in study (NCT06681766) is active, and the company has begun dosing adolescents.
Friedreich’s Ataxia Treatment Landscape and the Surrogate Endpoint Question
Friedreich’s ataxia is a progressive, autosomal recessive neurodegenerative disorder caused by a GAA trinucleotide repeat expansion in the FXN gene, leading to deficiency of the mitochondrial protein frataxin. The disease affects an estimated 5,000 individuals in the US. Onset typically occurs in childhood or adolescence, and the clinical course involves progressive ataxia, cardiomyopathy, scoliosis, and, in many cases, diabetes. No therapy has been approved that restores frataxin or modifies the underlying biology of the disease.
The only FDA-approved disease-targeted therapy is omaveloxolone (Skyclarys), a nuclear factor erythroid 2-related factor 2 (Nrf2) activator developed by Reata Pharmaceuticals and now marketed by Biogen, which received approval in February 2023 based on the Phase II/III MOXIe trial. Omaveloxolone acts downstream of the frataxin deficit, modulating oxidative stress pathways rather than replacing the deficient protein. Its approval represented a first for Friedreich’s ataxia treatment, but the mechanism does not address the root molecular cause.
Nomlabofusp, by contrast, is a recombinant fusion protein designed to deliver functional frataxin intracellularly, targeting the proximal deficiency. The concept originated in academic research on TAT-frataxin fusion constructs at Indiana University School of Medicine. The program was developed by Chondrial Therapeutics, which was acquired in 2020 by the company then known as Zafgen, Inc., subsequently renamed Larimar Therapeutics. Larimar retains all development and commercialization rights and has not entered into any co-development or out-licensing partnerships.
The use of skin frataxin as a surrogate endpoint is central to the accelerated approval strategy and is, by the FDA’s own framing, a matter that will be evaluated at the time of BLA review. The biological rationale — that restoring frataxin in peripheral tissue correlates with improvements in mitochondrial function and clinical outcomes — is supported by decades of research on the role of frataxin deficiency in FA pathophysiology, though no prior regulatory decision has validated tissue FXN as a registrational biomarker.