Nomlabofusp
Nomlabofusp (CTI-1601), recombinant frataxin fused to a cell penetrating peptide, for Friedreich ataxia
Written by Aaron CuhaReviewed Sep 2026
Also known as: CTI-1601
Human frataxin fused to a TAT derived cell penetrating peptide, injected subcutaneously to replace the protein missing in Friedreich ataxia. In 55 adults across two phase 1 trials it raised frataxin in buccal cells, skin and platelets; whether that changes the disease is the question of a 150 person phase 3 that began in August 2026 and reads out in 2029.
Overview
Friedreich ataxia is caused by too little frataxin, a mitochondrial protein, and nomlabofusp is an attempt to put the protein back. It is recombinant human frataxin joined to a cell penetrating peptide derived from HIV TAT, designed so the fusion crosses cell membranes and the mitochondrial import machinery cleaves it to release mature frataxin inside the mitochondrion. Larimar Therapeutics is developing it under the earlier code CTI-1601. It is a fusion protein rather than a peptide; the peptide is the delivery vehicle.
What has been measured in people is pharmacology, not clinical benefit. Two double blind, placebo controlled phase 1 trials enrolled 55 adults with Friedreich ataxia aged 19 to 69: a single ascending dose study of 25 to 100 mg (28 participants) and a multiple ascending dose study of up to 100 mg daily for 13 days (27 participants). Peak plasma levels came 15 minutes after subcutaneous injection, adverse events were mostly mild, there were no serious adverse events, and frataxin concentrations rose in buccal cells, skin and platelets with higher and more frequent dosing. A 2026 paper in patients and in mice, rats and primates reports that drug derived frataxin levels in skin and buccal cells track levels in heart, muscle and dorsal root ganglia across species, which is the argument for using those accessible tissues as a surrogate. An open label phase 2 (NCT06447025, estimated 85 participants) is recruiting with primary completion expected January 2027. A phase 3 (NCT07778836, estimated 150 participants) started on 5 August 2026 with primary completion projected for July 2029. A paediatric pharmacokinetic study (NCT06681766) was terminated after 18 participants for an administrative reason, to move children directly into the open label study; it was not a safety stop.
No randomised trial has yet measured whether nomlabofusp slows or reverses the neurological progression of Friedreich ataxia. Nomlabofusp is not approved anywhere.
Mechanism of action
In people, what is established is that subcutaneous nomlabofusp is absorbed quickly, that daily dosing raises frataxin measurably in buccal cells, skin and platelets, and that levels in those tissues correlate with each other. Whether frataxin reaches the tissues that matter most in Friedreich ataxia, the dorsal root ganglia, cerebellum and heart, in a person, has not been measured directly; the cross tissue correlations that support it come from animals. In cells and animals, the TAT derived sequence carries the fusion protein across the plasma membrane; the mitochondrial targeting sequence of frataxin directs it into the mitochondrion, where the fusion is processed to release mature frataxin. A 2025 AAPS Journal paper shows the released frataxin is functional in frataxin deficient cells. In mice, rats and primates, subcutaneous dosing distributes frataxin to heart, skeletal muscle, dorsal root ganglia and brain.
Human evidence
55 adults in two randomised placebo controlled phase 1 trials, 18 children and adolescents in a terminated pharmacokinetic study, and an open label phase 2 still recruiting. Every published human endpoint is safety, pharmacokinetics or frataxin concentration in accessible tissue. No trial has yet reported a clinical outcome.
- Single ascending dose phase 1: 28 adults, 25 to 100 mg or placebo. Well tolerated; no serious adverse events.
- Multiple ascending dose phase 1: 27 adults, up to 100 mg daily for 13 days or placebo. Frataxin rose in buccal cells, skin and platelets, more with higher and more frequent dosing. No serious adverse events.
- Cross tissue correlation (2026): in patients, frataxin levels in skin and buccal cells correlated; the link to heart and nerve tissue comes from animals.
- NCT06447025: open label phase 2, estimated 85 participants, recruiting, primary completion January 2027.
- NCT06681766: paediatric phase 1, 18 enrolled, terminated for an administrative reason (participants moved directly to the open label study).
- NCT07778836: phase 3, estimated 150 participants, started 5 August 2026, primary completion July 2029.
What this does not tell you: Raising frataxin in skin is not the same as slowing ataxia. Frataxin concentration is a surrogate for a protein deficiency disease, and it is a reasonable one, but the connection between peripheral frataxin and the heart and nervous system tissues that fail in Friedreich ataxia has only been demonstrated in animals. The longest controlled exposure is 13 days in 27 people. The long term study is open label and cannot measure efficacy against a comparator. The phase 3 that can will not read out before 2029.
Reading the research record
This is an orphan disease programme run by a single small sponsor, and its evidence base is exactly as mature as its stage: thorough pharmacology, a clean but short safety record, and a clinical efficacy question that has been asked but not yet answered. Larimar funded every study and employs most of the authors of the human papers, which is normal for a company at this stage and is stated here because it is the only source of data. The Friedreich's Ataxia Research Alliance, a patient organisation, is also represented among the authors. Nomlabofusp appears in peptide catalogues because of its TAT derived delivery sequence, but the active ingredient is a full length human protein, and it has no conceivable use outside the disease it is designed for.
The design choice worth watching is the surrogate. A protein replacement therapy for a rare disease can seek approval on a biomarker with confirmatory trials afterwards, and the 2026 cross tissue paper is building the case that skin and buccal frataxin can stand in for the tissues that cannot be biopsied. That argument is supported by animal data and by correlations among peripheral tissues in patients. Whether regulators accept it, and whether it translates into slower disease, are separate questions, and the second one is what the 2029 phase 3 readout is for.
The evidence, charted
Fig. 1 · evidence composition
5of 7 citations (71%) are in people
Counted from the citation list on this page. The Human count is the same number shown in the badge at the top. Both understate any literature larger than the sources we cite.
Fig. 2 · evidence over time
Evidence spans 3 distinct years, 2024 to 2026, counted from the citation list on this page.
Fig. 3 · legal status at a glance
US
Not approved
UK
Approved
AU
Approved
CA
Not approved
Approved in 2 of 4, prescription route in 0, not approved in 2. A jurisdiction's classification is a regulatory fact, not a verdict on the science; see Legal status below for the full text and any notes.
Key studies & citations
- Human2024
Safety, pharmacokinetics, and pharmacodynamics of nomlabofusp (CTI-1601) in Friedreich's ataxia
Two double blind placebo controlled phase 1 trials in adults aged 19 to 69 with Friedreich ataxia: single ascending dose 25 to 100 mg (28 participants) and multiple ascending dose up to 100 mg daily for 13 days (27 participants). Mostly mild adverse events, no serious adverse events or deaths; peak plasma levels at 15 minutes; frataxin rose in buccal cells, skin and platelets with higher and more frequent dosing. Funded by Larimar Therapeutics; most authors are or were Larimar employees.
Annals of Clinical and Translational Neurology - Human2026
Nomlabofusp Treatment Produces Frataxin Levels That Correlate Across Peripheral Tissues: Preclinical and Clinical Support for Surrogate Tissue Sampling
Drug derived frataxin measured after subcutaneous dosing in mice, rats, primates and patients with Friedreich ataxia. Levels in skin and buccal cells correlated with levels in heart, skeletal muscle and dorsal root ganglia across species, supporting those accessible tissues as surrogates for exposure. Tissue level correlations in animals; peripheral tissues only in patients. Funded by Larimar.
Clinical and Translational Science - In vitro2025
Nomlabofusp, a Fusion Protein of Human Frataxin and a Cell Penetrant Peptide, Delivers Mature and Functional Frataxin into Mitochondria
Shows that the fusion protein enters cells, is processed by mitochondrial peptidase to mature frataxin, and that the released frataxin is functional in frataxin deficient cells. Mechanistic; industry funded.
AAPS Journal - Animal2025
Pharmacokinetics and Pharmacodynamics of Nomlabofusp in Non-clinical Studies of Friedreich's Ataxia
Non-clinical pharmacokinetics and tissue distribution after subcutaneous dosing in animals, including delivery of frataxin to heart, muscle and nervous tissue. Animal data. Industry and NIH intramural support.
AAPS Journal - Human2026
A Study to Evaluate the Efficacy and Safety of Subcutaneous Nomlabofusp in Subjects With Friedreich's Ataxia (NCT07778836)
Phase 3, estimated 150 participants, started 5 August 2026, recruiting, primary completion projected July 2029. The first trial designed to measure clinical efficacy. Sponsor funded.
ClinicalTrials.gov, Larimar Therapeutics - Human2024
An Open-Label Study of CTI-1601 in Subjects With Friedreich's Ataxia (NCT06447025)
Phase 2, open label, estimated 85 participants, recruiting since January 2024, primary completion expected January 2027. Uncontrolled long term dosing study. Sponsor funded.
ClinicalTrials.gov, Larimar Therapeutics - Human2024
A Study to Assess Nomlabofusp in Adolescents and Children With Friedreich's Ataxia (NCT06681766)
Phase 1 paediatric pharmacokinetic study, terminated after 18 participants. Sponsor's stated reason: review of cohort 1 data allowed direct enrolment into the open label study and removed a pause in dosing. An administrative termination, not a safety or efficacy stop.
ClinicalTrials.gov, Larimar Therapeutics
Frequently asked questions
Does nomlabofusp treat Friedreich ataxia?
Not yet shown. In 55 adults it raised frataxin levels in buccal cells, skin and platelets over up to 13 days with mostly mild side effects. No trial has yet measured whether that changes neurological function or disease progression; the phase 3 designed to do so began in August 2026 and is projected to complete in July 2029.
Is nomlabofusp a peptide?
It is a fusion protein: full length human frataxin joined to a short cell penetrating peptide derived from the HIV TAT protein. The peptide is the delivery vehicle. Once inside the mitochondrion the fusion is cleaved and the frataxin released is identical to the native protein.
Was the paediatric trial stopped for safety?
No. NCT06681766 was terminated after 18 participants because, in the sponsor's words, review of the first cohort's data allowed children to enrol directly in the open label study without a pause in dosing. That is an administrative reason.
Is it approved anywhere?
No. It is investigational in every jurisdiction. The open label phase 2 is recruiting and the phase 3 started in August 2026.