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.

Keywords: abicipar pegol; age-related macular degeneration; anti-VEGF; choroidal neovascularization; optical coherence tomography; vascular endothelial growth factor.

Conflict of interest statement

Dr. Callanan is a consultant for Abbvie, Alcon, Allergan, Graybug Vision, Regeneron, Sanofi, and Santen and serves on the speakers' bureaus of Abbvie and Allergan. Dr. Kunimoto is a consultant to Genentech and Graybug Vision. Dr. Maturi is a consultant for Allergan and Graybug Vision and receives clinical research funding from Allergan, Allegro Pharmaceuticals, Genentech, and Santen. Dr. Patel is a consultant for Graybug Vision and Roche and has received support for clinical trials from Acucela, Alcon, Allergan, Apellis, Astellas, Genentech/Roche, Ophthotech, and Regeneron. Dr. Staurenghi is a consultant/advisor for Boehringer, Carl Zeiss Meditec, and Genentech; has received grant support from Centervue, Optos, and Optovue; is a consultant/advisor for and has received grant support from Heidelberg Engineering and Quantel Medical; is a consultant/advisor for and has received lecture fees from Alcon, Allergan, Bayer, GlaxoSmithKline, Novartis, and Roche; and has patents with royalties from Ocular Instruments. Dr. Wolf is a consultant for Alcon, Allergan, Bayer Healthcare, Heidelberg Engineering, Novartis, Roche, and Zeiss. Dr. Cheetham, Dr. Hohman, and Dr. Schneider were employees of Allergan at the time of this work. Dr. Kim and Dr. López are employees of Allergan.

Figures

FIG. 1.

Change in BCVA (letters) from baseline in the modified intent-to-treat population of patients treated with abicipar 1 mg (light green lines and squares; n = 25), abicipar 2 mg (dark green lines and squares; n = 23), or ranibizumab 0.5 mg (orange lines and circles; n = 16). Data shown are least-squares means ± standard errors from the mixed-effects model for repeated measures. There were no statistically significant differences between abicipar 1 mg or 2 mg and ranibizumab 0.5 mg in change in BCVA from baseline. Green and orange arrows indicate when the 3 abicipar injections or 5 ranibizumab injections were administered. Mean ± standard error of the mean BCVA at baseline for the abicipar 1 mg, abicipar 2 mg, and ranibizumab 0.5 mg arms was 58.4 ± 3.7, 58.5 ± 3.8, and 60.4 ± 4.1 letters, respectively. B, baseline. BCVA, best-corrected visual acuity.

FIG. 2.

Proportion (%) of patients in the modified intent-to-treat population gaining ≥15 letters of best-corrected visual acuity from baseline after treatment with abicipar 1 mg (light green bars; n = 25), abicipar 2 mg (dark green bars; n = 23), or ranibizumab 0.5 mg (orange bars; n = 16). Proportions are calculated for patients with data available who had not been rescued (unless rescued with ranibizumab in the ranibizumab group). There were no statistically significant differences between treatment arms. Green and orange arrows indicate when the 3 abicipar injections or 5 ranibizumab injections were administered.

FIG. 3.

Change from baseline in CRT (μm) in the modified intent-to-treat population of patients treated with abicipar 1 mg (light green lines and squares; n = 25), abicipar 2 mg (dark green lines and squares; n = 23), or ranibizumab 0.5 mg (orange lines and circles; n = 16). Data shown are least-squares means ± standard errors from the mixed-effects model for repeated measures. There were no statistically significant differences between abicipar 1 mg or 2 mg and ranibizumab 0.5 mg in change in CRT from baseline. Green and orange arrows indicate when the 3 abicipar injections or 5 ranibizumab injections were administered. Mean ± standard error of the mean CRT at baseline for the abicipar 1 mg, abicipar 2 mg, and ranibizumab 0.5 mg arms was 526 ± 33, 466 ± 26, and 463 ± 24 μm, respectively. B, baseline. CRT, central retinal thickness.

FIG. 4.

Proportion (%) of patients in the modified intent-to-treat population achieving resolution of the 3 fluid compartments of subretinal fluid, intraretinal cyst, and intraretinal fluid (an “all dry” retina) after treatment with abicipar 1 mg (light green bars; n = 25), abicipar 2 mg (dark green bars; n = 23), or ranibizumab 0.5 mg (orange bars; n = 16). Proportions are calculated for patients with data available who had not been rescued (unless rescued with ranibizumab in the ranibizumab group). Green and orange arrows indicate when the 3 abicipar or 5 ranibizumab injections were administered. *P = 0.017 versus ranibizumab; †P = 0.049 versus ranibizumab, ‡P = 0.003 versus ranibizumab.