Despite tolerability concerns, nomlabofusp’s overall efficacy represents a “large win” for Larimar, according to analysts at William Blair, who lauded the therapy’s functional benefits.
Larimar Therapeutics’ investigational frataxin therapy nomlabofusp significantly improved functional outcomes in an ongoing open-label study of patients with Friedreich’s ataxia—but safety signals have left investors disappointed. The biotech was down 33% at market close on Monday.
Data reported Monday showed that patients treated with daily nomlabofusp saw a substantial increase in frataxin levels at 6 months, with skin concentrations matching those in asymptomatic carriers. The drug also led to a “consistent directional improvement” in key functional outcomes, including fatigue and activities of daily living, findings that Larimar said suggest a “potential clinical benefit across a broad spectrum of patients” with Friedreich’s ataxia (FA).
Analysts at William Blair appeared to agree, telling investors in a Monday note that the frataxin improvement is “a large win” for nomlabofusp, while its functional benefits “have not been seen in an interventional FA trial to our knowledge.” Taken together, these results paint an “impressive” clinical efficacy profile for nomlabofusp, the analysts wrote.
Tolerability results, however, were mixed. In its news release on Monday, Larimar claimed that nomlabofusp was “generally well-tolerated” but revealed that seven of 39 treated patients had experienced anaphylaxis and needed to be pulled from the study. Following these cases, the biotech has decided to modify its starting dose regimen for nomlabofusp, which the FDA has agreed to.
Despite regulatory alignment on the changes, the anaphylaxis episodes “are undoubtedly a concern for investors,” William Blair said on Monday, noting that risks will remain “somewhat unknown” as Larimar moves toward a biologics license application in the second quarter of 2026.
Still, “the unmet need in FA remains high with no disease-modifying therapy currently available, and we still see a path forward for nomlabofusp approval here given impressive efficacy/biomarker data,” the analysts wrote.
Friedreich’s ataxia is a rare mitochondrial disorder that affects 1 in 50,000 people in the U.S. The disease is characterized by a deficiency in the frataxin protein, which is crucial for mitochondrial function. Patients with FA experience motor and other movement difficulties, fatigue and problems with speech or swallowing, among other symptoms.
Leading the FA space is Biogen with its Nrf2 agonist Skyclarys, which won the FDA’s approval in 2023. The drug has since become a major product for Biogen, bringing in $382.5 million worldwide last year.
Also in the FA game is PTC Therapeutics and its small-molecule drug vatiquinone, which inhibits key disease pathways. The drug’s development has been rocky, however. In May 2023, vatiquinone failed the Phase III MOVE-FA study when it did not significantly improve disease progression versus placebo. Last month, the FDA rejected vatiquinone, noting that “substantial evidence of efficacy was not demonstrated.”
