First Patient Dosed in Phase 2 Open Label Extension Study of Nomlabofusp for Friedreich Ataxia


Data from the phase 2 open label extension study investigating subcutaneous injections of nomlabofusp for Friedreich ataxia is expected in the fourth quarter of 2024.

 Carole Ben-Maimon, MD, president, and chief executive officer of Larimar

Carole Ben-Maimon, MD

Credit: Larimar Therapeutics

According to a recent announcement, the first patient has been dosed in a phase 2 open label extension (OLE) trial assessing 25 mg daily subcutaneous injections of nomlabofusp (Larimar Therapeutics), formally known as CTI-1601, in patients with Friedreich ataxia (FA). The initial data from the OLE study on nomlabofusp, a novel investigational protein replacement therapy designed to address the root cause of FA by delivering frataxin to mitochondria, is anticipated in the fourth quarter of 2024.1

The OLE study will investigate the safety and tolerability, pharmacokinetics, and tissue frataxin levels in peripheral tissues as well as other exploratory pharmacodynamic markers following treatment with nomlabofusp. During the trial, clinical measures collected will be compared with data from a synthetic control arm derived from patients from the Friedreich’s Ataxia Clinical Outcome Measures Study database. Additionally, data from the 50 mg cohort of the phase 2 dose exploration study and from the 25 mg dose in the OLE study will be submitted for FDA review to escalate the dose in the OLE study because of the continued partial clinical hold.

Top Clinical Takeaways

  • Nomlabofusp may represent a novel approach to treating Friedreich ataxia by targeting the root cause of the disease.
  • The phase 2 trial aims to assess both safety and efficacy parameters, including tissue frataxin levels, in patients with Friedreich ataxia.
  • Collaboration with regulatory authorities is essential to address any safety concerns and move the treatment forward.

“We are pleased to dose the first patient in our OLE study, further advancing the nomlabofusp clinical program and building on the successful completion of our phase 2 dose escalation study,” Carole Ben-Maimon, MD, president, and chief executive officer of Larimar, said in a statement.1 “Importantly, the OLE study will inform on the long-term safety profile and tissue frataxin levels and provide a first look at real-life experience with self-administration by patients or administration by a caregiver.”

READ MORE: FDA Grants Fast Track Designation for Gene Therapy Candidate LX2006 in Friedreich Ataxia Cardiomyopathy

In July 2023, the FDA cleared the company’s 4-week, placebo-controlled exploration trial (NCT05579691) assessing CTI-1601 in doses of 50 mg and the OLE.2 In the exploration trial, ambulatory and nonambulatory individuals with FA aged at least 18 years old will be randomly assigned 2:1 to either CTI-1601 or placebo daily via subcutaneous injections for the first 14 days, and then every other day until day 28. The trial features 2 cohorts, a 25 mg and 50 mg dosed group. Cohort 1, assessing a 25 mg dose of CTI-1601, includes 13 participants (9 on active treatment, 4 on placebo) while Cohort 2, which is initiating, will include 12-15 participants randomized to either CTI-1601 or placebo in 50 mg dose settings.

“Participants who completed treatment in the recent phase 2 dose exploration trial, or who previously completed a prior phase 1 clinical trial of nomlabofusp are potentially eligible to screen for the OLE. Based on our phase 1 and phase 2 findings, we expect to continue daily dosing throughout the study,” Ben-Maimon said.1

In May 2021, the CTI-1601 program was placed on clinical hold by the FDA after the company notified the FDA of mortalities that occurred at the highest dose levels in a 26-week nonhuman primate toxicology study. The company underwent a Type C meeting with the FDA to determine the next steps, and thus submitted a complete response that included unblinded safety, pharmacokinetic, and pharmacodynamic data from the phase 2 trial’s completed 25 mg cohort. This ultimately led to the FDA’s decision to advance the phase 2 trial to a 50 mg cohort and initiate its OLE.3

In May 2023, Larimar announced positive topline data from the phase 2 study with CTI-1601 which demonstrated a safe profile in doses of 25 mg and observed increases in FXN levels among treated patients. On day 14, a median placebo-adjusted increase from baseline was observed in frataxin levels in skin tissue (3.5 pg/ug) and buccal cells (0.9 pg/ug). Among 7 CTI-1601-treated participants, all demonstrated increases in skin FXN concentrations and 5 had increases in buccal cell FXN concentrations. In comparison, there were no increases in FXN concentrations observed in the skin tissue among the 4 participants on placebo and no increases in buccal cells in the 2 participants on placebo at the end of day 14.4

“In February we announced that we intend to pursue frataxin as a potential novel surrogate endpoint to support accelerated approval,” Ben-Maimon said in a statement.1 “The frataxin data, supportive pharmacodynamics and clinical outcomes information and safety data from the OLE study, along with additional nonclinical pharmacology information will be used to help support a potential BLA submission for accelerated approval targeted for the second half of 2025. We look forward to reporting initial data from the OLE study in the fourth quarter of 2024.”

1. Larimar Therapeutics Announces the Dosing of the First Patient in Long-term Open Label Extension Study for Nomlabofusp in Patients with Friedreich’s Ataxia. News Release. Larimar Therapeutics. Published March 11, 2024. Accessed April 30, 2024.
2. Larimar Therapeutics receives FDA clearance to proceed to 50 mg cohort in CTI-1601’s phase 2 Friedreich’s Ataxia trial and to initiate open label extension trial. News release. Larimar Therapeutics. July 25, 2023. Accessed April 30, 2024.
3. Larimar Therapeutics provided updates on CTI-1601 clinical program following a Type C meeting with the US Food and Drug Administration and reports second quarter 2022 operating and financial results. News release. Larimar Therapeutics. August 11, 2022. Accessed April 30, 2024.
4. Larimar Therapeutics Reports Preliminary Top-line Data from Phase 2 Trial’s 25 mg Cohort Showing Increases in Frataxin Levels in Patients with Friedreich’s Ataxia and First Quarter 2023 Financial Results. News Release. Larimar Therapeutics. Published May 15, 2023. Accessed April 30, 2024.
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