Aflibercept 8 mg Exhibits Non-Inferior Vision Gains in PULSAR, PHOTON Trials

David M. Brown, MD

Credit: Retina Consultants of Texas

One-year results from the pivotal PULSAR and PHOTON trials demonstrated extended dosing regimens with aflibercept 8 mg (EYLEA HD) were non-inferior to aflibercept 2 mg (EYLEA) for the treatment of wet age-related macular degeneration (AMD) and diabetic macular edema (DME).

According to the results, extended 12- or 16-week dosing regimens of aflibercept 8 mg exhibited non-inferior vision gains to standard-of-care aflibercept 2 mg with fixed 8-week dosing in the first year.

The one-year results for the two double-masked, active-controlled pivotal trials, PULSAR and PHOTON trials, were recently published in The Lancet.

“The publication of 48-week results from PULSAR and PHOTON in The Lancet is a recognition of the important advancement EYLEA HD has made in retinal care,” said David M. Brown, MD, director of research at Retina Consultants of Texas and a trial investigator, in a statement. “Less than a year after its approval, EYLEA HD has already made an impact in the treatment of wet AMD and DME.”

In August 2023, EYLEA HD received approval from the U.S. Food and Drug Administration for treating patients with wet AMD, DME, and diabetic retinopathy (DR) based on the one-year data. Two-year data were presented in 2023 for PULSAR at the EURETINA Congress and for PHOTON at the annual American Society of Retina Specialists meeting.

The 96-week, phase 3 PULSAR trial was conducted across 223 global sites, in which adults with nAMD were randomized to aflibercept 8 mg every 12 weeks, aflibercept 8 mg every 16 weeks, or aflibercept 2 mg every 8 weeks, after three initial monthly doses in all groups.

The phase 2/3 PHOTON trial was conducted at 138 hospitals and specialty retina clinics in 7 countries and enrolled eligible patients aged ≥18 years with type 1 or 2 diabetes and center-involved DME. These participants were randomly assigned 1:2:1 to aflibercept 2 mg every 8 weeks, aflibercept 8 mg every 12 weeks, or aflibercept 8 mg every 16 weeks after initial monthly dosing.

Across both trials, the primary end point was the change from baseline in best-corrected visual acuity (BCVA) at week 48. PULSAR (n = 1,009) and PHOTON (n = 658) met the primary study end point, demonstrating non-inferior and clinically equivalent vision gains at 48 weeks.

In PULSAR, in eyes with nAMD, aflibercept 8 mg every 12- or 16 weeks exhibited non-inferior vision gains versus every 8-week aflibercept 2 mg (mean change, +6.7 letters and +6.2 letters vs. +7.6 letters). In PHOTON, in eyes with DME, aflibercept 8 mg every 12- or 16 weeks showed non-inferior vision gains compared with every aflibercept 2 mg (mean change, +8.8 letters and +7.9 letters vs. +9.2 letters).

Results from PULSAR AND PHOTON showed 79% and 77% of patients with wet AMD and 91% and 89% of patients with DME, who were randomized to 12- and 16-week aflibercept 8 mg dosing, maintained these extended dosing windows through 48 weeks.

Overall, the most common adverse reactions (≥3%) in those treated with aflibercept 8 mg were cataract, conjunctival hemorrhage, increased intraocular pressure, ocular discomfort, blurry vision, vitreous floaters, vitreous detachment, corneal epithelium defect, and retinal hemorrhage.

“EYLEA HD has provided disease control for my tough-to-treat cases of diabetic eye disease and allowed both my diabetic and wet AMD patients to enjoy less frequent dosing, with a similar safety profile to EYLEA,” Brown added.

References

1. _{Eylea® HD (aflibercept) injection 8 mg pivotal data in wet age-related macular degeneration (wamd) and diabetic macular edema (DME) published in the Lancet. Regeneron Pharmaceuticals Inc. March 8, 2024. Accessed March 8, 2024. https://investor.regeneron.com/news-releases/news-release-details/eylear-hd-aflibercept-injection-8-mg-pivotal-data-wet-age.}
2. _{Brown DM, Boyer DS, Do DV, et al. Intravitreal aflibercept 8 mg in diabetic macular edema (PHOTON): 48-week results from a randomized, double-masked, non-inferiority, phase 2/3 trial. The Lancet. March 7, 2024. Accessed March 8, 2024. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)02577-1/abstract.}
3. _{Lanzetta P, Korobelnik J-F, Heier JS, et al. Intravitreal aflibercept 8 mg in neovascular age-related macular degeneration (PULSAR): 48-week results from a randomized, double-masked, non-inferiority, phase 3 trial. The Lancet. March 7, 2024. Accessed March 8, 2024. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)00063-1/abstract.}
4. _{Campbell P. Aflibercept 8 mg (eylea HD) approved by FDA for wet AMD, DME, and Diabetic retinopathy. HCP Live. August 23, 2023. Accessed March 8, 2024. https://www.hcplive.com/view/aflibercept-8mg-eylea-hd-approved-by-fda-for-wamd-dme-and-diabetic-retinopathy.}