Larimar's Friedreich's Ataxia Drug Shows Promise Despite Safety Concerns

Nomlabofusp Demonstrates Efficacy in Open-Label Study

Larimar Therapeutics has reported significant improvements in functional outcomes for patients with Friedreich's ataxia (FA) treated with its investigational frataxin therapy, nomlabofusp. In an ongoing open-label study, patients receiving daily doses of nomlabofusp experienced a substantial increase in frataxin levels after six months of treatment. Skin concentrations of frataxin in treated patients matched those found in asymptomatic carriers, suggesting a potential breakthrough in addressing the underlying cause of FA.

The drug also showed promise in improving key functional outcomes, including reduced fatigue and enhanced ability to perform 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 noted that such functional benefits "have not been seen in an interventional FA trial to our knowledge," underscoring the potential significance of nomlabofusp in the treatment landscape.

Safety Concerns and Regulatory Response

Despite the encouraging efficacy data, nomlabofusp's development has been marred by safety concerns. Larimar reported that seven out of 39 treated patients experienced anaphylaxis, necessitating their withdrawal from the study. This revelation led to a 33% drop in Larimar's stock price at market close on Monday.

In response to these adverse events, Larimar has decided to modify the starting dose regimen for nomlabofusp. The U.S. Food and Drug Administration (FDA) has agreed to this adjustment, potentially paving the way for continued development. However, William Blair analysts noted that the anaphylaxis episodes "are undoubtedly a concern for investors," and risks will remain "somewhat unknown" as Larimar progresses towards a biologics license application, expected in the second quarter of 2026.

Competitive Landscape in Friedreich's Ataxia Treatment

Friedreich's ataxia, a rare mitochondrial disorder affecting approximately 1 in 50,000 people in the U.S., is characterized by a deficiency in the frataxin protein crucial for mitochondrial function. The disease leads to motor difficulties, fatigue, and problems with speech and swallowing, among other symptoms.

Currently, Biogen's Skyclarys, an Nrf2 agonist approved by the FDA in 2023, leads the FA treatment space. The drug 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 lack of substantial evidence of efficacy.

Despite the safety concerns surrounding nomlabofusp, William Blair analysts maintain that "the unmet need in FA remains high with no disease-modifying therapy currently available." They see a potential path forward for nomlabofusp's approval, given its "impressive efficacy/biomarker data" in addressing this critical gap in FA treatment.