Double-Masked, Randomized, Phase 2 Evaluation of Abicipar Pegol (an Anti-VEGF DARPin Therapeutic) in Neovascular Age-Related Macular Degeneration

Abstract

Purpose: To evaluate safety and efficacy of the vascular endothelial growth factor binding protein abicipar pegol (abicipar) versus ranibizumab for neovascular age-related macular degeneration.Methods: Phase 2, multicenter, randomized, double-masked comparison (REACH study, stage 3). Patients (n = 64) received intravitreal injections of abicipar 1 mg or 2 mg at baseline, week 4, and week 8 (3 injections) or ranibizumab 0.5 mg at baseline and monthly (5 injections).Results: In the abicipar 1 mg (n = 25), abicipar 2 mg (n = 23), and ranibizumab (n = 16) arms, respectively, least-squares mean best-corrected visual acuity (BCVA) change from baseline was +6.2, +8.3, and +5.6 letters at week 16 (primary endpoint) and +8.2, +10.0, and +5.3 letters at week 20. Least-squares mean central retinal thickness (CRT) reduction from baseline was 134, 113, and 131 μm at week 16 and 116, 103, and 138 μm at week 20. Intraocular inflammation adverse events (AEs), reported in 5/48 (10.4%) abicipar-treated patients, resolved without sustained vision loss or other sequelae.Conclusions: Abicipar demonstrated durability of effect: BCVA and CRT improvements were similar between abicipar and ranibizumab at weeks 16 and 20 (8 and 12 weeks after the last abicipar injection and 4 weeks after the last ranibizumab injection). No serious AEs were reported.

A Mechanistic and Translational Pharmacokinetic-Pharmacodynamic Model of Abicipar Pegol and Vascular Endothelial Growth Factor Inhibition

“…In the REACH phase 2 study, abicipar groups had visual acuity improvements that were numerically greater than ranibizumab at week 16, corresponding to 8 weeks after the final abicipar injection (Callanan et al, 2018). This difference for treatment groups was sustained at week 20, corresponding to 12 weeks after the final abicipar injection (Callanan et al, 2018). Our model simulation also suggests that the Q16 treatment may be a feasible dose in some patients in terms of maintaining the VEGF inhibition during a 52-week treatment period.…”

“…Our model predictions align with the visual acuity outcomes in REACH phase 2 study and CEDAR and SEQUOIA phase 3 studies. In the REACH phase 2 study, abicipar groups had visual acuity improvements that were numerically greater than ranibizumab at week 16, corresponding to 8 weeks after the final abicipar injection (Callanan et al, 2018). This difference for treatment groups was sustained at week 20, corresponding to 12 weeks after the final abicipar injection (Callanan et al, 2018).…”

“…In phase II and III trials, abicipar 1 and 2 mg demonstrated sustained effectiveness in patients with nAMD. In the REACH phase 2 study, abicipar was effective in patients with nAMD at 8-12 weeks after receiving the last injection of abicipar (Callanan et al, 2018). Both 1 or 2 mg of abicipar produced greater improvements in best-corrected visual acuity with fewer IVT injections administered than 0.5 mg ranibizumab (Callanan et al, 2018).…”

“…In the REACH phase 2 study, abicipar was effective in patients with nAMD at 8-12 weeks after receiving the last injection of abicipar (Callanan et al, 2018). Both 1 or 2 mg of abicipar produced greater improvements in best-corrected visual acuity with fewer IVT injections administered than 0.5 mg ranibizumab (Callanan et al, 2018). In the CEDAR and SEQUOIA identical phase III studies, abicipar (2 mg 8week or quarterly dosing) demonstrated noninferiority compared with ranibizumab (0.5 mg dosed monthly) on the primary endpoint of stable vision at week 52 (Rodrigues et al, 2018).…”

The role of steroids in treating diabetic macular oedema in the era of anti-VEGF

“…New drugs emerge with pronounced anti-inflammatory effect like faricimab (Roche, Genentech) targeting both angiopoietin-2 and VEGF-A [23] and drugs with longer duration of action such as brolucizumab (Novartis) [24], and abicipar pegol (Allergan) [25]. New slow release devices such as the port delivery system will enable us to reduce the number of injections.…”