PULSAR Trial Shows Durability of Aflibercept 8 mg in Wet AMD at 2 Years

Credit: v2osk/Unsplash

Positive, topline 2-year data from the pivotal PULSAR trial indicate durable vision gains and extended dosing intervals with aflibercept 8 mg treatment in patients with wet age-related macular degeneration (AMD).¹

These longer-term data follow positive 2-year results for the PHOTON study in diabetic macular edema (DME), with both trials able to demonstrate the majority of patients treated with aflibercept 8 mg were able to maintain or further extend their dosing intervals.²

“It is great to see aflibercept 8 mg deliver another set of exciting results,” trial investigator Charles C. Wykoff, MD, PhD, director of research at Retina Consultants of Texas, said in a statement. In the PULSAR trial, aflibercept 8mg achieved impressive durability, while importantly maintaining visual acuity gains from year one through year two. 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 aflibercept (EYLEA).”

Including more than 1,000 patients, the PULSAR study 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 of aflibercept injection (n = 336). All patients included in PULSAR received 3 initial monthly doses.

Last year, the PULSAR trial met its primary endpoint with patients treated with aflibercept 8 mg achieving clinically equivalent vision gains to aflibercept. Now, through 2 years of study, the vision gains were sustained and mainly remained consistent with the 1-year results.

Among patients who completed the 2-year PULSAR follow-up, 88% were on ≥12-week dosing intervals at the end of the 2-year period. Moreover, results showed 78% maintained ≥12-week dosing intervals throughout the 2-year study period, compared with 83% in the first year of study (48 weeks).

The analysis showed 71% met extension criteria for longer dosing intervals, including 47% for ≥20-week intervals and 28% for 24-week intervals.

For 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% of patients were eligible for ≥16-week dosing and 53% were eligible for ≥20-dosing week intervals.

Safety analyses in PULSAR showed aflibercept 8 mg continued to be similar to aflibercept through 2 years and remained consistent with the known safety profile observed in previous clinical trials for wet AMD. The investigative team observed no cases of retinal vasculitis, occlusive retinitis, or endophthalmitis in the aflibercept 8 mg group.

The analysis showed the rate of intraocular inflammation was 1.3% for the aflibercept 8 mg group and 2.1% for the aflibercept group. Additionally, 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 aflibercept.

In June, the US Food and Drug Administration (FDA) filed a Complete Response Letter (CRL) in response to Regeneron’s biologics license application for aflibercept 8 mg as a treatment of patients with wet AMD, DME, and diabetic retinopathy.³

The CRL pertained “solely” to an ongoing review of findings from a third-party filler inspection and did not identify any issues with clinical efficacy or safety, trial design, labeling, or drug substance manufacturing. No additional clinical data or trials were requested by the FDA.

“If approved by regulatory authorities, aflibercept 8 mg has the potential to become the new standard of care for diabetic macular edema and wet AMD,” Wykoff said.

References

1. Two-year pulsar trial results for aflibercept 8 mg demonstrate durable vision gains at extended dosing intervals in wet age-related macular degeneration. Regeneron Pharmaceuticals Inc. August 10, 2023. Accessed August 10, 2023. https://investor.regeneron.com/news-releases/news-release-details/two-year-pulsar-trial-results-aflibercept-8-mg-demonstrate.
2. Aflibercept 8 mg two-year results from pivotal photon trial in diabetic macular edema presented at ASRS. Regeneron Pharmaceuticals Inc. July 29, 2023. Accessed August 10, 2023. https://investor.regeneron.com/news-releases/news-release-details/aflibercept-8-mg-two-year-results-pivotal-photon-trial-diabetic.
3. Iapoce C, Kunzmann K. FDA issues complete response letter for Aflibercept 8 mg as AMD, DME treatment. HCP Live. July 7, 2023. Accessed August 10, 2023. https://www.hcplive.com/view/fda-issues-complete-response-letter-aflibercept-8-mg-amd-dme.