Abstract
Purpose :
There is an unmet need for longer-acting treatments that reduce the treatment burden associated with anti-vascular endothelial growth factor (anti-VEGF) therapy in neovascular age-related macular degeneration (nAMD). Abicipar is a DARPin anti-VEGF therapy optimized for duration by balancing high affinity binding, a long half-life in the vitreous, and high molar dose. Two phase 3 studies compared the efficacy and safety of 2 dosing regimens of abicipar versus monthly ranibizumab in patients with treatment-naïve nAMD.
Methods :
Two 2-year, multicenter, randomized (1:1:1; 1 eye/patient), double-masked, identically designed phase 3 studies (CEDAR, SEQUOIA). Patients received intravitreal abicipar 2 mg every 8 weeks after initial doses at baseline, Week 4, and Week 8 (Q8), abicipar 2 mg every 12 weeks after initial doses at baseline, Week 4, and Week 12 (Q12), or ranibizumab 0.5 mg every 4 weeks (Q4). Primary efficacy endpoint: proportion of patients with stable vision (<15-letter loss from baseline) at Week 52. For patients who remained on therapy, secondary efficacy endpoints at Week 104 included patients (%) with stable vision and mean changes from baseline in best-corrected visual acuity (BCVA) and central retinal thickness (CRT). Safety measures included treatment-emergent adverse events (TEAEs). Pooled data from both studies were used for analysis.
Results :
Abicipar Q8 and Q12 both met the primary endpoint of noninferiority to ranibizumab Q4 in the primary endpoint of stable vision at Week 52. At Week 104, the proportion of patients with stable vision was similar in the abicipar Q8 (93% [n=426]), abicipar Q12 (90% [n=422]), and ranibizumab Q4 (94% [n=498]) arms. Week 104 mean gains in BCVA from baseline were 7.8, 6.1, and 8.5 letters, and mean changes in CRT from baseline were −147, −146, and −142 μm, in the abicipar Q8 (14 injections), abicipar Q12 (10 injections), and ranibizumab Q4 (25 injections) arms, respectively. The overall incidence of intraocular inflammation TEAEs was 15.4%, 15.3%, and 0.3% from baseline through Week 52 and 0.8%, 2.3%, and 1.0% from Week 52 through Week 104.
Conclusions :
DARPin anti-VEGF therapy represents a powerful new technology that extends the duration of effect of anti-VEGF therapy and reduces treatment burden. Two-year results of the CEDAR and SEQUOIA studies confirm the efficacy and safety of quarterly dosing with abicipar in nAMD.
This is a 2020 ARVO Annual Meeting abstract.