Larimar's Nomlabofusp Shows Promise for Friedreich's Ataxia, Despite Safety Concerns

Larimar Therapeutics has reported significant improvements in functional outcomes for patients with Friedreich's ataxia (FA) treated with its investigational frataxin therapy, nomlabofusp. However, safety concerns have dampened investor enthusiasm, leading to a 33% drop in the company's stock price.

Efficacy Results and Functional Benefits

In an ongoing open-label study, patients receiving daily nomlabofusp treatment demonstrated a substantial increase in frataxin levels after six months. Skin concentrations of frataxin matched those found in asymptomatic carriers, suggesting a potential for disease modification.

The drug also showed "consistent directional improvement" in key functional outcomes, including reduced fatigue and improved activities of daily living. These findings indicate a "potential clinical benefit across a broad spectrum of patients" with FA, according to Larimar.

Analysts at William Blair have described the frataxin improvement as "a large win" for nomlabofusp, noting that the observed functional benefits "have not been seen in an interventional FA trial to our knowledge."

Safety Concerns and Regulatory Response

Despite the promising efficacy data, tolerability results were mixed. Seven out of 39 treated patients experienced anaphylaxis, necessitating their withdrawal from the study. In response, Larimar has decided to modify the starting dose regimen for nomlabofusp, a change that has received FDA agreement.

The anaphylaxis episodes "are undoubtedly a concern for investors," according to William Blair analysts. They noted that risks will remain "somewhat unknown" as Larimar progresses toward a biologics license application, expected in the second quarter of 2026.

Market Context and Competition

Friedreich's ataxia, affecting 1 in 50,000 people in the U.S., is characterized by a deficiency in the frataxin protein crucial for mitochondrial function. Patients experience motor difficulties, fatigue, and problems with speech and swallowing.

Currently leading the FA treatment space is Biogen's Skyclarys, an Nrf2 agonist approved by the FDA in 2023. Skyclarys has become a major product for Biogen, generating $382.5 million in worldwide sales last year.

PTC Therapeutics is also active in FA drug development with vatiquinone, a small-molecule drug inhibiting key disease pathways. However, vatiquinone's development has faced setbacks, including a failed Phase III study and recent FDA rejection citing insufficient evidence of efficacy.

Despite the safety concerns surrounding nomlabofusp, William Blair analysts remain optimistic about its potential, citing the high unmet need in FA and the lack of currently available disease-modifying therapies. They see a path forward for nomlabofusp's approval, given its "impressive efficacy/biomarker data."