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Purpose: To analyse pooled safety data of intravitreal bevacizumab gamma across all trials included within the NORSE clinical programme for nAMD.

Methods: Post-hoc safety analysis included all eyes receiving ≥1 intravitreal injection of bevacizumab gamma for nAMD across the NORSE clinical programme.

Results: A total of 432 eyes received intravitreal bevacizumab gamma for treatment of nAMD. Mean age 78.7yrs, 67.6% female; 68.1% treatment-naïve. Mean drug exposure across studies ranged from 89 to 335 days. The safety population reflected a real-world demographic, as participants were not excluded based on prior cardiovascular or neurologic history; 28.6% had a history of cardiac disorder, including prior myocardial infarction (n=16) or transient ischemic attack (n=15). Ocular treatment emergent adverse events (AEs) related to bevacizumab gamma or injection procedure occurred in 11.8%, slightly lower among previously treated eyes (9.3%) compared with treatment-naïve eyes (11.9%). Most common ocular AEs were post-injection conjunctival haemorrhage (3.7%) and increased IOP (2.1%). Vitreous detachment and vitreous haemorrhage each occurred in 1%. No cases of retinal artery occlusion, retinal vasculitis, choroiditis, retinal tears, or retinal detachment were reported. Less than 1% of treatment-related ocular AEs were Grade ≥3, including transient blindness with increased IOP, iritis, iridocyclitis, and endophthalmitis (n=1 each), all resolved without sequalae. Overall, 7.4% experienced at least one SAE; however, <1% were considered related to bevacizumab gamma or injection procedure. Thirty-seven systemic SAEs were reported. The most common non-serious systemic AEs were urinary tract infection (7.6%) and hypertension (3.2%). Four deaths occurred across all studies; none related to treatment or study procedures. Study discontinuation due to AEs was uncommon (n=8 [1.9%]).

Conclusions: This pooled analysis represents the largest safety dataset reported for intravitreal bevacizumab gamma to date. In a population reflective of real-world patients with substantial cardiovascular comorbidity, bevacizumab gamma demonstrated an anticipated ocular and systemic safety profile with rates of adverse events comparable to other VEGF-inhibiting therapies. These findings support the favourable safety profile of intravitreal bevacizumab gamma and its continued use in the management of nAMD. A further comparison of safety findings of bevacizumab gamma and other intraocular anti-VEGF agents will be presented.