Regeneron Announces Topline Phase 2 Data of High-Dose Aflibercept in Wet AMD

Regeneron Pharmaceuticals announced that an ongoing phase 2 proof-of-concept trial evaluating an investigational 8 mg dose of aflibercept met its primary safety endpoint, with no new safety signals observed compared to the currently-approved 2 mg dose of Eylea (aflibercept) injection in patients with wet age-related macular degeneration (AMD). In this small trial involving 106 patients, a higher proportion of patients in the aflibercept 8 mg group had no retinal fluid (43.4%, n=23/53) compared to patients treated with Eylea 2 mg (26.4%, n=14/53) (p=0.067) at week 16, the primary efficacy endpoint. At this time point, patients had received three initial doses (administered at weeks 0, 4 and 8), after which dosing was extended.

Aflibercept 8 mg is currently being evaluated in two large phase 3 trials in wet AMD and diabetic macular edema (DME), which are expected to report results in the second half of 2022. The trials will assess the safety and efficacy of aflibercept 8 mg for up to 2 years, with visual acuity as the primary efficacy endpoint at 48 weeks, measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA). Both trials will assess aflibercept 8 mg compared to Eylea 2 mg, testing dosing intervals of every 12 weeks and every 16 weeks.

“We are cautiously optimistic that these early data suggest that a higher dose of aflibercept may potentially benefit patients with wet AMD, and we look forward to phase 3 data next year, which will be crucial to understand its overall efficacy and safety,” George D. Yancopoulos, MD, PhD, President and Chief Scientific Officer of Regeneron, said in a company news release. “Having worked for nearly two decades in retinal disease, we know that large, robust data sets are required to fully understand whether a medicine can achieve three critical things: improved visual and anatomic outcomes, convenient dosing, and a safety profile that is consistent with Eylea.”

During the initial 16 weeks of the phase 2 trial, adverse events (AEs) in the study eye occurred in 17.0% (9 of 53) of aflibercept 8 mg patients and 22.6% (12 of 53) of Eylea 2 mg patients. Serious ocular AEs occurred in two patients overall, one in the aflibercept 8 mg group (retinal tear) and one in the Eylea 2 mg group (visual acuity reduced). There were no AEs of intraocular inflammation (including occlusive retinal vasculitis), anti-platelet trialists’ collaboration (APTC)-defined arterial thromboembolic events or deaths in either patient group.

Aflibercept 8 mg is being jointly developed by Regeneron and Bayer.