PULSAR: Aflibercept 8mg Shows Noninferiority to Aflibercept 2mg in nAMD Treatment

Credit: v2osk/Unsplash

Results from the PULSAR trial indicate aflibercept 8mg met the primary efficacy endpoint in eyes with neovascular age-related macular degeneration (nAMD), showing non-inferiority to aflibercept 2 mg and no new safety signals through 48 weeks of study.¹

The data, presented in a symposium at the American Society of Retina Specialists (ASRS) 41st Annual Scientific Meeting, showed the majority of patients were able to extend both ≥12-week dosing (83% in aflibercept 8mg combined) and 16-week dosing (77% in 8q16).

“Overall, aflibercept 8 mg provides greater therapeutic benefit, an extended injection interval, and equivalent safety versus aflibercept 2 mg,” wrote the investigative team, led by Jignesh Patel, MD, an attending retinal specialist at Colchester Hospitals University Foundation Trust.

The PULSAR trial evaluated the efficacy and safety of intravitreal aflibercept 8 mg injection administrated every 12 or 16 weeks versus aflibercept 2mg every 8 weeks, each after 3 initial monthly injections in patients with treatment-naive nAMD.² Investigators sought to determine the therapeutic benefit, injection interval, and safety of aflibercept 8mg compared to aflibercept 2mg in this population.

The trial is an ongoing, double-masked, 96-week, phase 3 trial, wherein patients aged ≥50 years with nAMD were randomly assigned 1:1:1 to receive 12-week aflibercept 8 mg injections, 16-week aflibercept 8mg injections, or 8-week aflibercept 2mg injections. The primary endpoint was BCVA change from baseline at Week 48, considered a non-inferiority margin at 4 letters.

Meanwhile, the key secondary endpoint was the proportion of patients with no intraretinal or subretinal fluid in the central subfield at Week 16, as well as safety. Other exploratory endpoints included the proportion of patients with ≥12-week and 16-week treatment intervals through Week 48.

A total of 1,009 patients were evaluated in the analysis, consisting of 54.5% female patients and with a mean age of 74.5 years. Of this population, 335 patients received aflibercept 8 mg every 12 weeks, 338 patients received aflibercept 8mg every 16 weeks, and 336 patients received aflibercept 2 mg every 8 weeks.

Upon analysis, the investigative team found the primary endpoint was met with aflibercept 8 mg (every 12-week aflibercept 8 mg vs. every 8-week aflibercept 2 mg: P = .0009; every 16-week aflibercept 8mg vs. every 8-week aflibercept 2mg: P = .0011). The observed mean change from baseline in BCVA at Week 48 was 6.7 ± 12.6 (baseline: 59.9 ± 13.4), 6.2 ± 11.7 (baseline: 60.0 ± 12.4), and 7.6 ± 12.2 letters (baseline, 58.9 ± 14.0) with every 12-week aflibercept 8 mg, every 16-week aflibercept 8mg, and every 8-week aflibercept 2 mg, respectively.

For those in the 12-week aflibercept 8mg group, the analysis showed 79% of patients (n = 316) maintained 12-week treatment intervals, and 77% of patients in the 16-week aflibercept 8mg (n = 312) maintained 16-week treatment intervals at 1-year.

Overall, 83% (n = 628) of patients receiving aflibercept 8mg maintained ≥12-week treatment intervals at 1 year. Moreover, aflibercept 8mg showed superior drying versus aflibercept 2 mg at Week 16. According to the data, 63% versus 52% of patients, respectively, had no intraretinal or subretinal fluid in the central subfield (P = .0002). Safety data reported similar safety profiles between aflibercept 8 mg and aflibercept 2mg.

References

1. Patel J, PULSAR Study Investigators. Intravitreal Aflibercept 8 mg Injection in Patients With Neovascular Age-Related Macular Degeneration: 48-week Results From the Phase 3 PULSAR Trial. Paper presentation at the American Society of Retina Specialists 41st Annual Meeting. July 28 - August 1.
2. Study to gather information on safety and use of high dose AFLIBERCEPT injection into the eye in patients with an age related eye disorder that causes blurred vision or a blind spot due to abnormal blood vessels that leak fluid into the light sensitive lining inside the eye - full text view. ClinicalTrials.gov. Accessed July 29, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04423718.