Background: Friedreich’s ataxia (FA) is a hereditary neurodegenerative disease that results from a deficiency in frataxin (FXN). Nomlabofusp is a recombinant fusion protein developed to increase FXN levels in adults and children with FA. Data from an ongoing open label (OL) study evaluating long term administration of nomlabofusp in patients with FA were reviewed.
Objective: Evaluate interim observations related to FXN levels, clinical measures, and safety in patients with FA receiving long term administration of nomlabofusp
Methods: Enrolled subjects received daily administration of nomlabofusp. Skin FXN levels and key clinical measures (mFARS, FARS_ADL, MFIS, 9HPT) were measured at baseline and every three months. Safety evaluations were performed monthly either during in person or remote study visits.
Results: Data from 39 subjects who received at least 1 dose of nomlabofusp were reviewed. Subjects received nomlabofusp treatment for up to 18 months. Median baseline skin FXN level was 2.7 pcg/mcg (16.5% of healthy controls). Mean age at screening and symptom onset were 30.2 and 12.7 years, respectively. Mean baseline results for mFARS, FARS_ADL, MFIS, and 9HPT were 55.7, 17.5, 33.2 points and 95.4 seconds, respectively. After 6 months of nomlabofusp treatment (n=10) median FXN levels increased to 13.4 pcg/mcg (82.2% of healthy controls); all 10 subjects had FXN levels that were above 50% of healthy controls. After 1 year of nomlabofusp treatment (n=8) clinical measure median values decreased (mFARS -2.25, FARS_ADL -0.50, MFIS -6.50, 9HPT -7.40). Mild-moderate injection site reactions were the most commonly reported adverse events. Within the first 42 days of treatment anaphylaxis was observed in 7 subjects and most occurred on Day 1: 6 of 7 subjects were exposed to nomlabofusp during a prior study. Frequency of adverse events decreased after the first 3 months of treatment.
Conclusion: In patients with FA, daily administration of nomlabofusp for 6 months resulted in increased skin FXN to levels that were within the range expected in asymptomatic carriers with no phenotypic expression of disease. After 1 year of nomlabofusp treatment, values from clinical measures trended lower, suggesting a potential for clinical improvement in the context of increased FXN levels. There is a risk of anaphylaxis during early treatment, particularly in patients who had past exposure to nomlabofusp. Long term treatment with nomlabofusp appeared to be well tolerated.