Regeneron Presents 2-Year PULSAR Trial Results for Aflibercept 8 MG in Wet AMD

Regeneron announced positive, 2-year (96 weeks), topline data from the pivotal PULSAR trial investigating aflibercept 8 mg in patients with wet age-related macular degeneration (AMD). During the trial, aflibercept 8 mg patients were initially randomized to either 12- or 16-week dosing intervals (after three initial monthly doses) and were able to shorten or extend dosing intervals if prespecified criteria were met, according to a company news release.

The longer-term data follow the 2-year results for PHOTON with diabetic macular edema (DME), with PULSAR similarly demonstrating that the vast majority of aflibercept 8 mg patients with wet AMD were able to maintain or further extend their dosing intervals. Among those who completed the 2-year follow-up:

• 88% were on a ≥12-week dosing interval at the end of 2 years
• 78% maintained ≥12-week dosing intervals throughout the 2-year study period, compared to 83% throughout the first year of study (48 weeks)
• 71% met the extension criteria for even longer dosing intervals, including 47% for ≥20-week intervals and 28% for 24-week intervals
• Of those assigned to ≥16-week dosing regimen at baseline, 70% maintained ≥16-week dosing intervals throughout the 2-year study period. At the end of 2 years, 78% were eligible for ≥16-week dosing, with 53% eligible for ≥20-dosing week intervals

“It is great to see aflibercept 8 mg deliver another set of exciting results,” Charles C. Wykoff, MD, PhD, Director of Research at Retina Consultants of Texas and a trial investigator, said in a company news release. “In the PULSAR trial, aflibercept 8 mg achieved impressive durability, while importantly maintaining visual acuity gains from year 1 through year 2. These data are consistent with the results from the PHOTON trial in diabetic macular edema, with both trials demonstrating a consistent safety profile with substantially fewer treatments than Eylea. If approved by regulatory authorities, aflibercept 8 mg has the potential to become the new standard of care for diabetic macular edema and wet age-related macular degeneration.”

PULSAR (N= 1,009) is a double-masked, active-controlled pivotal trial evaluating non-inferiority of aflibercept 8 mg 12-week (n=335) and 16-week (n=338) dosing regimens compared to an 8-week dosing regimen for Eylea (aflibercept) injection (n=336). All patients received three initial monthly doses. The PULSAR trial met its primary endpoint last year with aflibercept 8 mg patients achieving clinically equivalent vision gains to Eylea. Through 2 years, vision gains were sustained and remained largely consistent with the results at 1 year.

In PULSAR, the safety of aflibercept 8 mg continued to be similar to Eylea through 2 years and remained consistent with the known safety profile of Eylea from previous clinical trials for wet AMD. There were no cases of retinal vasculitis, occlusive retinitis or endophthalmitis in the aflibercept 8 mg group. The rate of intraocular inflammation was 1.3% for the aflibercept 8 mg group, and 2.1% for the Eylea group. Anti-platelet trialists' collaboration-defined arterial thromboembolic treatment-emergent adverse events occurred in 1.8% of patients treated with aflibercept 8 mg and 3.3% of patients treated with Eylea.

The 2-year data from PULSAR are planned for presentation at an upcoming medical meeting. The 2-year data from the pivotal PHOTON trial for aflibercept 8 mg in DME were presented at the American Society of Retina Specialists annual meeting in July 2023.

During its second quarter conference call, Regeneron said it anticipates the FDA will take action on its biologics license application (BLA) for high-dose aflibercept during the third quarter.