Regeneron Reports Positive Phase 2 Results for High-Dose Aflibercept 8 mg in Wet Age-Related Macular Degeneration

On February 11, 2022, Regeneron Pharmaceuticals announced positive results from a proof-of-concept Phase 2 clinical trial of aflibercept for the treatment of wet age-related macular degeneration (AMD). The trial aimed to evaluate the efficacy and safety of an investigational 8 mg high-dose level of aflibercept compared to the approved 2 mg dose level of aflibercept (marketed as Eylea). At 44 weeks, the trial met its primary safety endpoint with no new safety signals observed. Moreover, patients in the 8 mg dose group showed improvements in vision and other anatomical measures compared to the control group. Results from the Phase 3 clinical trials of aflibercept (8 mg) for wet AMD and diabetic macular edema (DME) are expected in the second half of 2022.

Wet AMD is the leading cause of vision loss in people over 60 years old, with approximately 20 million patients worldwide. The growth of abnormal blood vessels, known as choroidal neovascularization (CNV), into the macula can lead to leakage of fluid and blood, causing scar tissue proliferation and subsequent damage to the central retina.

Aflibercept is an ocular injectable solution with the main component being a vascular endothelial growth factor (VEGF) inhibitor. Its mechanism of action involves blocking the growth factors VEGF-A and placental growth factor, which are involved in angiogenesis, thereby inhibiting new blood vessel formation and reducing intraocular vascular permeability. The 8 mg dose level of aflibercept was jointly developed by Regeneron and Bayer. This novel concentrated high-dose formulation increases the amount of medication delivered per treatment and has the potential to extend dosing intervals while maintaining the efficacy and safety profiles observed at the approved dose levels.

This randomized, single-blind Phase 2 clinical trial enrolled 106 treatment-naïve patients with wet AMD. Patients were randomly assigned to receive either 8 mg or 2 mg of aflibercept. Efficacy endpoints were assessed by evaluating the presence of retinal fluid in the central subfield using optical coherence tomography (OCT). Previously published results showed that at week 16, 51% of patients in the 8 mg group had no fluid in the central subfield (p=0.0770), compared to 34% in the 2 mg group.

Key results at 44 weeks are shown below:

40% (n=21/53) of patients in the 8 mg group and 28% (n=15/53) of patients in the 2 mg group had no fluid in the central subfield (p=0.2185).

32% (n=17/53) of patients in the 8 mg group had no macular fluid, twice that of the 2 mg group (15%, n=8/53) (p=0.0395). Compared with the central subfield, the retinal area assessed for macular fluid is larger and may provide a better understanding of the anatomical effects of treatment.

According to the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score, the 8 mg group showed an average improvement of 7.9 letters from baseline, compared to 5.1 letters in the 2 mg group (p=0.1957).

Nearly half (47%) of the patients in the 8 mg group achieved a visual acuity improvement of at least 10 letters, and more than a quarter (28%) experienced an improvement of over 15 letters. The corresponding values for the 2 mg group were 35% and 18%, respectively.

At 44 weeks, the safety profiles of the two groups were similar.

References:

[1] Regeneron Presents Encouraging Phase 2 Results For High-Dose Aflibercept 8 Mg In Wet Age-Related Macular Degeneration At Angiogenesis Meeting. Retrieved February 11, 2022, from https://investor.regeneron.com/news-releases/news-release-details/regeneron-presents-encouraging-phase-2-results-high-dose

(Original text has been abridged)

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