PULSAR Phase 3 trial 96-week results: Robust treatment response with aflibercept for nAMD

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Reviewed by Sunir Garg, MD

Sunir Garg, MD, reported the 96-week results of the effects of aflibercept 8 mg intravitreal injections (Eylea HD, Regeneron Pharmaceuticals) to treat neovascular age-related macular degeneration (AMD) at the Hawaiian Eye meeting in Maui.

He reported the findings on behalf of the PULSAR study investigators. He is from Mid Atlantic Retina, The Retina Service of Wills Eye Hospital, Thomas Jefferson University, Philadelphia.

The principle finding of this phase 3 trial was that aflibercept 8 mg demonstrated similar improvements in best-corrected visual acuity (BCVA) and central subfield thickness (CST) compared to the 2 mg dose of aflibercept, through week 96 among treatment-naïve patients with neovascular AMD.

The PULSAR Study

In this randomized study, patients with neovascular AMD were assigned to 1 of 3 treatment groups, i.e., aflibercept 2 mg every 8 weeks, aflibercept 8 mg every 12 weeks, or aflibercept 8 mg every 16 weeks after 3 initial monthly doses. The primary efficacy endpoint was the mean change in BCVA from baseline at week 48 (with a non-inferiority margin of 4 letters), Garg recounted.

The results showed that at weeks 48 and 96, the 2 groups treated with aflibercept 8 mg demonstrated non-inferior BCVA gains compared to aflibercept 2 mg administered every 8 weeks. The non-inferiority P values at week 96 for aflibercept 8mg every 12 and 16 weeks were 0.0006 (nominal) and 0.0007 (nominal), respectively.

The improvements in CST were similar in the 3 treatment arms, with minimal fluctuations throughout treatment.

The mean numbers of injections through week 96 were 12.8, 9.7, and 8.2, respectively, in the 2-mg group and in the 8mg groups with injections administered every 12 and 16 weeks.

Garg reported that “the vast majority of patients maintained the dosing interval they were assigned to at baseline with 78% of patients treated with aflibercept 8 mg every 16 weeks having last assigned treatment intervals that were at least 16 weeks and 53%having last assigned dosing intervals that were at least 20 weeks."

Importantly, the investigators found no new ocular safety signals for aflibercept 8 mg compared with aflibercept 2 mg.

“It’s tremendous to see such a robust response to treatment with 3-quarters of patients being able to be dosed every 16 weeks, while having a similar safety profile as the 2-mg dose we have used for more than a decade,” Garg concluded.