Nomlabofusp

Friedreich's ataxia is caused by an expanded GAA repeat in the FXN gene, which leaves the body short of frataxin, a protein that supports mitochondria, the cell's energy centers^[13]. Nerve cells and the heart are hit hardest, which is why balance and coordination problems and a thickened heart muscle are common^[13]. Nomlabofusp is the complete human frataxin protein joined to a short cell-penetrating peptide, a tag that helps it get inside cells; inside mitochondria the tag is cut off to leave mature frataxin^[5].

Larimar describes it as a protein replacement therapy designed to address frataxin deficiency, the underlying cause of the disease^[1]. Skyclarys (omaveloxolone), the approved treatment, does not replace frataxin, and its label says its exact mechanism is unknown^[12].

The FDA filing rests on skin frataxin levels from the open-label study (NCT06447025)^[1][7]. Larimar reported in June 2026 that mean skin frataxin rose from 3.7pg/µg at baseline to 12.5pg/µg at 3 months, and that all 9 participants measured at 12 months were above 8.2pg/µg, a level Larimar set at about half the healthy volunteer average^[2].

Larimar also reported what it called directional improvement on the mFARS ataxia rating scale and other measures at 1 year in 13 participants, compared with a natural history group of untreated patients rather than a placebo group^[2]. FORWARD-FA (NCT07778836) is the Phase 3 study meant to confirm a clinical benefit: a randomized, double-blind, placebo-controlled comparison of daily nomlabofusp for 72 weeks, with change in the mFARS upright stability score and total mFARS as primary outcomes^[6].

ClinicalTrials.gov lists ages 12 to 40 and 150 participants, while Larimar's November 2026 release describes ambulatory participants aged 2 to 40 who are new to the drug^[6][1].

Anaphylaxis, a severe allergic reaction, is the main safety finding so far^[2]. Larimar reported in June 2026 that 10 participants in the open-label study had anaphylaxis, 9 of whom had received nomlabofusp in an earlier study; the release gives the total as 10 of 43 in its highlights and 10 of 41 in its body^[2]. Of 11 participants with no prior exposure, 1 had anaphylaxis, and every case returned to baseline health after standard treatment^[2].

Larimar's August 2026 update said those 10 participants left the study^[3]. Larimar also reported generalized hives in 3 participants, with no new cases after antihistamine therapy began^[2], and its August 2026 update said those 3 also left the study^[3]. Larimar reported mild to moderate injection site reactions, the most common side effect, which became less frequent over time and led no one to stop^[2].

When it granted Breakthrough Therapy designation, the FDA said the adequacy of the safety database would be a matter of review when the application is submitted^[4].

Larimar first tested the drug, then called CTI-1601, in Phase 1 studies completed in 2020 and 2021, in which side effects were mostly mild and frataxin rose with higher and more frequent doses^[5][8][9]. MedCity News reported on May 26, 2021 that the FDA had placed the program on clinical hold after monkeys died at the highest dose in a toxicology study^[10].

NeurologyLive reported on May 21, 2024 that Larimar announced the FDA had removed the remaining partial hold after reviewing Phase 2 data^[11]. Larimar announced on February 24, 2026 that the FDA had granted Breakthrough Therapy designation, and the drug also holds Fast Track, Rare Pediatric Disease and Orphan Drug designations^[4][1]. Larimar completed its rolling BLA on November 9, 2026 and has said it expects FDA acceptance in early 2027 and, if approved, a decision in mid-2027^[1].