Draft:Nomlabofusp

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Nomlabofusp
INN: nomlabofusp
Clinical data
Other namesCTI-1601, TAT-frataxin
Routes of
administration		Subcutaneous
ATC code
  • none
Legal status
Legal status
  • Investigational (not approved)
Identifiers
CAS Number

Nomlabofusp (development code CTI-1601) is an investigational frataxin protein replacement therapy being developed by Larimar Therapeutics for the treatment of Friedreich's ataxia (FA), a rare inherited neurodegenerative disease caused by deficiency of the protein frataxin.[1][2] It was originally developed at Chondrial Therapeutics and was discovered by R. Mark Payne at the Indiana University School of Medicine.[3][4] As of mid-2026 it had not been approved by any regulatory agency and remained in clinical development.[5]

Mechanism

Nomlabofusp is a recombinant fusion protein consisting of a cell-penetrating peptide fused to human frataxin, the protein that is deficient in Friedreich's ataxia.[1][2] It is designed to deliver frataxin across cell membranes and into the mitochondria, with the goal of supplementing the underlying frataxin deficiency.[1] It is administered by subcutaneous injection.[1]

In non-clinical studies, subcutaneously administered nomlabofusp was reported to distribute to tissues affected in the disease, and the authors reported that the protein was processed toward mature frataxin within mitochondria.[2]

Clinical development

Nomlabofusp originated at Chondrial Therapeutics under the development code CTI-1601 and was later developed by Larimar Therapeutics.[3][1]

Two Phase 1, double-blind, placebo-controlled studies were conducted in adults with Friedreich's ataxia: a single-ascending-dose study (Clinical trial number NCT04176991 at ClinicalTrials.gov) and a multiple-ascending-dose study (Clinical trial number NCT04519567 at ClinicalTrials.gov).[1]

In May 2021, the U.S. Food and Drug Administration (FDA) placed a clinical hold on the program after deaths occurred at the highest dose levels in a long-term non-human primate toxicology study; no patients had been dosed in the planned Phase 2 trial at that time.[6] The hold was partially lifted in September 2022, allowing a Phase 2 placebo-controlled dose-exploration study to begin, and was fully removed in May 2024.[6][7] A long-term open-label extension study in adults subsequently began, and a pharmacokinetic study in adolescents aged 12–17 was conducted in early 2025.[6]

Regulatory status

Nomlabofusp has received several expedited-development designations. In 2017, the FDA granted orphan drug designation to CTI-1601 for Friedreich's ataxia.[3] The therapy was subsequently granted Fast Track and Rare Pediatric Disease designations by the FDA, orphan drug designation by the European Commission, and PRIME designation by the European Medicines Agency.[4] In February 2026, the FDA granted nomlabofusp Breakthrough Therapy Designation for the treatment of adults and children with Friedreich's ataxia.[5]

Larimar Therapeutics stated that it planned to begin a rolling Biologics License Application (BLA) submission seeking accelerated approval in mid-2026, using skin frataxin levels as a proposed surrogate endpoint, with a confirmatory Phase 3 study planned to be underway around the time of submission.[5][8] As of mid-2026, the therapy had not received marketing approval.[5]

References

  1. Clayton, Russell; Galas, Teresa; Scherer, Noreen; Farmer, Jennifer; Ruiz, Nancy; Hamdani, Mohamed; Schecter, Devin; Bettoun, David (March 2024). "Safety, pharmacokinetics, and pharmacodynamics of nomlabofusp (CTI-1601) in Friedreich's ataxia". Annals of Clinical and Translational Neurology. 11 (3): 540–553. doi:10.1002/acn3.51971. PMID 38311797.
  2. De Toni, Flavia; Ragaglia, Vanessa; Schecter, Devin; Miller, Angela S.; Gonzalez, Eric; Wagner, Erik J.; Xu, Xin; Payne, R. Mark; Mess, Jean-Nicholas; Baile, Matthew G.; Clements-Egan, Adrienne; Shankar, Gopi (June 2025). "Pharmacokinetics and Pharmacodynamics of Nomlabofusp in Non-clinical Studies of Friedreich's Ataxia". The AAPS Journal. 27. Article 112. doi:10.1208/s12248-025-01093-y.
  3. "Chondrial Announces FDA Orphan Drug Designation for CTI-1601, a Novel Investigational Technology for the Treatment of Friedreich's Ataxia" (Press release). Chondrial Therapeutics. August 3, 2017. Retrieved June 20, 2026 – via PR Newswire.
  4. "Nomlabofusp". Larimar Therapeutics. Retrieved June 20, 2026.
  5. "Larimar Therapeutics Announces FDA Breakthrough Therapy Designation for Nomlabofusp in FA and Reiterates Planned BLA Submission in June 2026" (Press release). Larimar Therapeutics. February 24, 2026. Retrieved June 20, 2026 – via GlobeNewswire.
  6. "Nomlabofusp (CTI-1601)". Friedreich's Ataxia Research Alliance. Retrieved June 20, 2026.
  7. "Larimar Therapeutics Announces FDA has Removed Partial Clinical Hold for Nomlabofusp Program in Friedreich's Ataxia" (Press release). Larimar Therapeutics. May 20, 2024. Retrieved June 20, 2026.
  8. "Larimar Advances Nomlabofusp Toward 2026 BLA Submission". The Globe and Mail. March 10, 2026. Retrieved June 20, 2026.