FDA Removes Partial Clinical Hold on Larimar’s Friedreich’s Ataxia Program

Rare Daily Staff

The U.S. Food and Drug Administration has removed the partial clinical hold previously placed on Larimar Therapeutics’ nomlabofusp clinical program for the treatment of patients with Friedreich’s ataxia.

Friedreich’s ataxia (FA) is an ultra-rare, inherited neurodegenerative disorder that is typically diagnosed during adolescence. Patients with Friedreich’s ataxia experience progressive loss of coordination, muscle weakness, and fatigue, which commonly progresses to motor incapacitation and wheelchair reliance by their teens or early twenties, and eventually death. Friedreich’s ataxia affects approximately 5,000 diagnosed patients in the United States.

Nomlabofusp is a novel protein replacement therapy designed to address the root cause of FA by delivering frataxin to mitochondria. The FDA removed the partial clinical hold after a review of data from the company’s recently completed four-week, placebo-controlled phase 2 dose exploration study. The review included data from both the 25 mg and 50 mg cohorts in patients who received daily dosing of nomlabofusp for 14 days followed by every other day dosing until day 28.

“we are now cleared to dose escalate to the 50 mg dose in our ongoing OLE study which we plan to do following further characterization of frataxin PD at the 25 mg dose,” said Carole Ben-Maimon, president, and CEO of Larimar. “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.”

In the phase 2 dose exploration study, nomlabofusp was generally well-tolerated throughout the four-week treatment period. Nomlabofusp had a predictable pharmacokinetic profile and demonstrated dose-dependent increases in frataxin levels in skin and buccal cells. All patients with quantifiable levels at baseline and Day 14 in the 50 mg cohort achieved frataxin levels in skin cells over 33 percent of the average level observed in healthy volunteers at Day 14, and 3 patients achieved levels greater than 50 percent of the average healthy volunteer level.

The long-term safety and tolerability, pharmacokinetics, and frataxin levels in peripheral tissues following nomlabofusp are currently being evaluated in the ongoing OLE study in patients with FA. The OLE study will initially evaluate daily subcutaneous injections of 25 mg of nomlabofusp self-administered or administered by a caregiver. Larimar plans to dose escalate to 50 mg in the OLE study following additional characterization of frataxin PD at the 25 mg dose. Further dose escalation above 50 mg, if necessary, would require submission of additional data for FDA review to support the increased dose. Interim data from the OLE study is expected in the fourth quarter of 2024. A Biologics License Application (BLA) submission is targeted for the second half of 2025.

Nomlabofusp has been granted Rare Pediatric Disease, Fast Track, and Orphan Drug designations by the U.S. Food and Drug Administration (FDA), Orphan Drug designation by the European Commission, and a PRIME designation by the European Medicines Agency.

Photo: Carole Ben-Maimon, president, and CEO of Larimar