Twenty-four-week data from the FIREFLEYE randomized phase 3 study suggest intravitreal aflibercept for treatment of acute-phase retinopathy of prematurity (ROP) in premature neonates is not associated with clinically relevant effects on blood pressure, further systemic adverse events, or immunogenicity.
Infants (gestational age ≤32 weeks or birthweight ≤1500 g) with treatment-requiring ROP in ≥1 eye were randomized 2:1 to receive aflibercept 0.4 mg or laser photocoagulation at baseline in the 24-week, randomized, open-label, noninferiority, phase 3 study. Endpoints include concentrations of free and adjusted bound aflibercept in plasma, pharmacokinetic/pharmacodynamic exploration of systemic anti-vascular endothelial growth factor effects, and immunogenicity.
Of 113 treated infants included in the study, 75 received aflibercept 0.4 mg per eye at baseline (mean age: 10.4 weeks), mostly bilaterally (71 infants), and with 1 injection/eye (120/146 eyes). Concentrations of free aflibercept were highly variable, with maximum concentration at day 1, declining thereafter. Plasma concentrations of adjusted bound (pharmacologically inactive) aflibercept increased from day 1 to week 4, decreasing up to week 24. Six infants experienced treatment-emergent serious adverse events within 30 days of treatment; aflibercept concentrations were within the range observed in other infants.
No pattern was observed between free and adjusted bound aflibercept concentrations and blood pressure changes up to week 4. A low-titer (1:30), non-neutralizing, non-clinically relevant treatment-emergent anti-drug antibody response was reported in 1 infant.
Reference
Stahl A, Azuma N, Wu WC, et al; FIREFLEYE Study Group. Systemic exposure to aflibercept after intravitreal injection in premature neonates with retinopathy of prematurity: results from the FIREFLEYE randomized phase 3 study. Eye (Lond). 2024;doi:10.1038/s41433-023-02919-9
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