A therapy that ferries a missing protein into mitochondria just completed its FDA approval application

Edited by Samael A. Tejada, Founder & Editor-in-Chief

Most drug applications are paperwork around clinical endpoints. This one is paperwork around a measurement — how much frataxin shows up in the skin — and whether the FDA will accept it as standing in for benefit.

What is nomlabofusp designed to do?

Friedreich's ataxia is caused by deficiency of frataxin, a mitochondrial protein. Nomlabofusp is an investigational recombinant fusion protein intended to correct that deficiency at its source by delivering human frataxin into mitochondria — a protein-replacement strategy aimed at the underlying cause rather than symptoms. It holds the FDA's Breakthrough Therapy, Fast Track, Rare Pediatric Disease and Orphan Drug designations, and was selected for the FDA's START pilot programme for rare-disease therapeutics.

On what evidence does the application rest?

Data from an ongoing long-term open-label study, including increases in skin frataxin concentration. In minutes from a multidisciplinary Type B pre-BLA meeting, the FDA confirmed the data appeared capable of supporting submission and review, and reaffirmed its willingness to consider skin frataxin as a potential novel surrogate endpoint for accelerated approval. The submission includes adolescents aged 12 to 17; currently, no Friedreich's ataxia therapy is approved for children under 16. Surrogate-based accelerated approval is explicitly provisional: it requires the benefit to be verified afterwards.

What happens next?

Verification is already designed: FORWARD-FA, a global, double-blind, placebo-controlled phase 3 study, is enrolling ambulatory participants aged 2 to 40 who are new to nomlabofusp, evaluating daily subcutaneous use over 18 months for safety and clinical outcomes. Larimar's stated timeline anticipates BLA acceptance in early 2027 and possible US approval by mid-2027, with a launch targeted for the third quarter of 2027 if approved. Each of those steps is the company's expectation, not the FDA's commitment — and accelerated approvals in rare diseases have been granted, delayed and withdrawn before.

Where the evidence stands

• Established: Friedreich's ataxia is driven by frataxin deficiency inside mitochondria, and no therapy is approved for patients under 16. Nomlabofusp carries Breakthrough Therapy, Fast Track, Rare Pediatric Disease and Orphan Drug designations.
• Preliminary: Skin frataxin as a surrogate for clinical benefit: accepted by the FDA as a basis for submission and review of an accelerated-approval application, not yet validated by an approval or by confirmatory outcomes.
• Absent: An FDA decision, and completed confirmatory evidence that raising frataxin improves how patients function or feel.