Dual inhibition of Ang-2 and VEGF-A with faricimab in diabetic macular edema: Evidence for increased durability from the BOULEVARD phase 2 trial

Abstract

Purpose : Faricimab, the first bispecific antibody designed for intraocular use, binds and neutralizes both angiopoietin-2 (Ang-2) and vascular endothelial growth factor A (VEGF-A). Owing to the role of the angiopoietin/Tie signaling pathway in vascular stabilization, it is hypothesized that Ang-2 inhibition may provide increased durability over anti-VEGF monotherapy in diabetic macular edema (DME).

Methods : BOULEVARD (NCT02699450) evaluated the efficacy and safety of faricimab in patients with centre-involving DME. Anti–VEGF treatment-naïve (N=168 enrolled) and previously anti–VEGF-treated patients (N=61 enrolled) received intravitreal 0.3 mg ranibizumab, 1.5 mg faricimab (treatment-naïve only), or 6.0 mg faricimab, administered every 4 weeks for 20 weeks. The primary efficacy outcome was mean change in best-corrected visual acuity (BCVA) from baseline at week 24 in treatment-naïve patients. In a 16-week off-treatment observation period, durability was assessed by time-to-retreatment using pre-specified BCVA and optical coherence tomography central subfield thickness (CST) criteria.

Results : BCVA and CST improved from baseline in all treatment arms. In treatment-naïve patients, patients receiving 6.0 mg faricimab achieved statistically significant greater BCVA gains over ranibizumab (+3.6 letters, P=0.03) at Week 24. Patients treated with faricimab experienced greater reductions in mean macular cube volume from baseline at week 24 in both treatment-naïve (1.5 mg faricimab, -2.83 mm³; 6.0 mg faricimab, -2.51 mm³) and previously treated (6.0 mg faricimab, -2.46 mm³) patients than with ranibizumab (treatment-naïve, -1.53 mm³; previously-treated, -1.43 mm³). During the observation period, faricimab showed potential for longer time to retreatment compared with ranibizumab in both patient populations. Additional analyses of durability from the off-treatment observation period will be presented.

Conclusions : BOULEVARD met its primary endpoint: faricimab demonstrated greater visual acuity gains versus ranibizumab at week 24 in treatment-naïve patients. Additional analysis of phase 2 data suggests faricimab has a potential for extended durability in both treatment-naïve and previously treated patients compared with anti-VEGF monotherapy. Durability of faricimab will be further explored in the ongoing phase 3 YOSEMITE (NCT03622580) and RHINE (NCT03622593) studies.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.