Larimar Completes BLA Seeking Accelerated Approval of Nomlabofusp for Friedreich’s Ataxia

Larimar Therapeutics has completed its rolling Biologics License Application (BLA) submission to FDA seeking accelerated approval of nomlabofusp, an investigational protein replacement therapy for Friedreich’s ataxia (FA).¹ The submission is based on increases in skin frataxin (FXN) concentrations as a potential novel surrogate endpoint, and Larimar expects FDA to accept the BLA in early 2027, with a potential approval in mid-2027.¹

“Completing our BLA submission is a major milestone for Larimar and the FA community, bringing years of development work together in an application seeking accelerated approval of nomlabofusp,” said Carole Ben-Maimon, MD, chief executive officer of Larimar.¹

What is nomlabofusp?

FA is an inherited neurodegenerative disorder that causes progressive loss of coordination, muscle weakness, and fatigue, and it is typically diagnosed during adolescence.² It affects approximately 5,000 diagnosed patients in the US.² The disease is driven by a deficiency of frataxin, a protein thought to play a role in mitochondrial energy production.³

Nomlabofusp is a recombinant fusion protein designed to address that underlying cause by delivering human frataxin to mitochondria.¹˒³ Larimar said nomlabofusp could become the first disease-modifying therapy for FA.¹ Skyclarys (omaveloxolone), which FDA approved in February 2023 as the first drug for FA, is indicated for patients aged 16 years and older.² Jen Farmer, MS, chief executive officer of the Friedreich’s Ataxia Research Alliance, noted that the submission includes data from adolescents aged 12 to 17, which she called “especially meaningful.”¹

The program has had setbacks. FDA placed a clinical hold on nomlabofusp in 2021 after deaths occurred at higher doses in nonhuman primate studies, then converted it to a partial hold in 2022 that limited trials to a 25-mg dose.³ The agency lifted the partial hold in May 2024 after reviewing phase 2 dose-exploration data.³

What data support the submission?

The BLA is supported by an ongoing long-term open-label study.¹ In previously reported findings, all evaluable participants at one year reached skin FXN levels within the range expected in asymptomatic heterozygous carriers, and directional improvements were observed across multiple clinical outcomes relative to worsening in a natural history reference population.¹ Exploratory pharmacodynamic markers, including plasma lipids and peripheral tissue gene transcription, also showed directional improvement compared with placebo-treated patients.¹

“It is important to note that patients with FA are expected to experience continued neurologic decline, not improvement,” Ben-Maimon said.¹

According to Larimar, FDA confirmed in minutes from a Type B pre-BLA meeting that the existing data package appears capable of supporting submission and review of a BLA seeking accelerated approval, though approval will be a matter of review.¹ FDA also reaffirmed its willingness to consider skin FXN as a novel surrogate endpoint and indicated that Larimar’s exposure-response analysis linking nomlabofusp exposure to clinical outcomes is the type of analysis that could support the submission.¹

Expedited pathways still require developers to meet rigorous evidence standards. In a BioPharm International® Drug Digest video interview on expedited regulatory pathways for biologics, Steven Quay, MD, PhD, founder and chief executive officer of Atossa Therapeutics, cautioned, “You don’t think that an expedited pathway that can get you an approval faster allows you to do less work.”

Nomlabofusp holds Breakthrough Therapy, Fast Track, Rare Pediatric Disease, and Orphan Drug designations, and it was selected for FDA’s Support for Clinical Trials Advancing Rare Disease Therapeutics (START) pilot program.¹ If approved, Larimar expects to receive a rare pediatric disease priority review voucher, which it plans to monetize.¹

What happens next?

Accelerated approval requires confirmatory evidence of clinical benefit. Larimar is enrolling patients in FORWARD-FA, a global, double-blind, placebo-controlled phase 3 study that will evaluate daily subcutaneous nomlabofusp over 18 months in ambulatory participants aged 2 to 40 who are new to the drug.¹ About two-thirds of participants will be younger than 21, reflecting the tendency for faster disease progression in younger patients.¹

Larimar plans an open-label safety update in the first quarter of 2027 and is targeting a US launch in the third quarter of 2027, if approved.¹ The company also plans to use its intracellular delivery platform to design other fusion proteins for rare diseases caused by deficiencies in intracellular bioactive compounds.¹

References

1. Larimar Therapeutics completes rolling BLA submission seeking accelerated approval of nomlabofusp for Friedreich’s ataxia. News release. Larimar Therapeutics; November 9, 2026. Accessed November 10, 2026.
2. Hippensteele A. FDA approves omavaloxolone, the first drug indicated for patients with Friedreich’s ataxia. Pharmacy Times. Published March 1, 2023. Accessed November 10, 2026.
3. Barrie R. Larimar resumes nomlabofusp programme after FDA lifts partial hold. Pharmaceutical Technology. Published May 21, 2024. Accessed November 10, 2026.