FDA Removes Partial Clinical Hold on Nomlabofusp Program for Friedreich Ataxia


Larimar Therapeutics anticipates interim data from the open label extension study assessing nomlabofusp in patients with Friedreich Ataxia in the fourth quarter of 2024.

Carole Ben-Maimon, MD  (Credit: Larimar)

Carole Ben-Maimon, MD

(Credit: Larimar)

According to a recent announcement, following the review of data from a phase 2 dose exploration study (NCT05579691), the FDA has removed the partial clinical hold previously placed on the clinical program of Larimar Therapeutics' nomlabofusp, formally known as CTI-1601, for the treatment of patients with Friedreich Ataxia (FA).1 The data reviewed included findings from both the 25 mg and 50 mg cohorts in participants who received daily dosing of nomlabofusp for 14 days followed by every other day dosing until day 28.

In the phase 2 study, results demonstrated that nomlabofusp, a novel protein replacement therapy aimed to address the root cause of FA through delivery of frataxin to mitochondria, was generally well-tolerated among participants throughout the 4-week treatment period. The treatment revealed a predictable pharmacokinetic profile and showed a dose-dependent increase in frataxin levels in skin and buccal cells. All participants with quantifiable levels at baseline and day 14 in the 50 mg cohort achieved frataxin levels in skin cells over 33% of the average level reported in healthy volunteers at day 14, and 3 patients achieved levels greater than 50% of the average healthy volunteer level.2

“We are very excited the FDA has removed the partial clinical hold on our nomlabofusp program following review of our phase 2 data. Helping patients with FA is our top priority and we appreciate the attention and thorough review by the FDA of all submitted data,” Carole Ben-Maimon, MD, president, and chief executive officer at Larimar, said in a statement.1 “Importantly, we are now cleared to dose escalate to the 50 mg dose in our ongoing open label extension (OLE) study which we plan to do following further characterization of frataxin PD at the 25 mg dose. The OLE study is evaluating the long-term safety as well as frataxin levels following daily administration of nomlabofusp and we look forward to interim data in the fourth quarter of the year.”

Top Clinical Takeaways

  • The FDA has lifted the clinical hold on CTI-1601 after reviewing positive phase 2 data.
  • Nomlabofusp was well-tolerated and showed significant increases in frataxin levels in patients with Friedreich Ataxia.
  • Larimar Therapeutics plans further dose escalation in the ongoing OLE study, with interim data expected by the end of 2024.

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Currently, investigators are assessing the long-term safety and tolerability, pharmacokinetics, and frataxin levels in peripheral tissues following nomlabofusp treatment in the ongoing OLE study. This study will initially assess daily subcutaneous injections of 25 mg of nomlabofusp self-administered or administered by a caregiver among patients with FA. The company plans to escalate the dose to 50 mg in the study after additional characterization of frataxin PD at the 25 mg dose.

Larimar noted in the announcement that any necessary further dose escalation above 50 mg would need submission of additional data for the FDA review to support this increase in dose. The company also noted that it anticipates interim data from the OLE study in the fourth quarter of 2024.

In May 2021, the nomlabofusp 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 completed 25 mg cohort of the phase 2 trial. 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 nomlabofusp 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 nomlabofusp -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

1. Larimar Therapeutics Announces FDA has Removed Partial Clinical Hold for Nomlabofusp Program in Friedreich’s Ataxia. News Release. Larimar Therapeutics. Published May 20, 2024. Accessed May 21, 2024. https://investors.larimartx.com/news-releases/news-release-details/larimar-therapeutics-announces-fda-has-removed-partial-clinical
2. Larimar Therapeutics Reports Positive Top-line Data from Phase 2 Dose Exploration Study from 25 mg and 50 mg Cohorts of Nomlabofusp in Patients with Friedreich’s Ataxia. News Release. Published February 12, 2024. Accessed May 21, 2024. https://investors.larimartx.com/news-releases/news-release-details/larimar-therapeutics-reports-positive-top-line-data-phase-2-dose
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 May 21, 2024. https://investors.larimartx.com/news-releases/news-release-details/larimar-therapeutics-provides-updates-cti-1601-clinical-program
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 May 21, 2024. https://www.globenewswire.com/news-release/2023/05/15/2668588/0/en/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.html
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