Alejandra Maiz, MD
Ophthalmology Resident, University of Michigan
The 2023 Annual Retina Society Meeting kicked off its third day and second age-related macular degeneration session with several outstanding talks. Dr. Michael Singer, clinical professor at the University of Texas Health Science Center in San Antonio, presented subgroup analysis results for patients with polypoidal choroidal vasculopathy (PCV) in the Phase 3 PULSAR trial.
The PULSAR trial (NCT04423718) is a, double-masked, Phase 3 trial in patients with treatment-naïve neovascular age-related macular degeneration. Participants are randomly assigned 1:1:1 to intravitreal aflibercept 8 mg every 12 or 16 weeks (8q12, 8q16) or 2 mg every 8 weeks (2q8), after a series of three initial monthly injections. A subgroup of these patients with indocyanine green angiography (ICGA) proven PCV were analyzed separately. The primary endpoint was change from baseline in best-corrected visual acuity (BCVA) at week 48. The secondary endpoint was the proportion of patients with no intraretinal/subretinal fluid (IRF/SRF) in central subfield at Week 16.
Dr. Singer quickly pointed out that the primary endpoint was successfully met in this group of patients, which is classically very difficult to treat. With a noninferiority margin at 4 letters, change from baseline in BCVA was similar among the three groups (6.7±12.6 (8q12), 6.2±11.7 (8q16), and 7.6±12.2 (2q8) letters). The proportion of patients with no central IRF/SRF was also similar in the pooled 8 mg intravitreal aflibercept group (67.8%) versus those who received the standard 2 mg (63.0%). Eighty patients in the 8q12 or 8q16 subgroup analysis were successfully followed for a total of 48 weeks, 69 (86.3%) of whom were able to be maintained on ≥12-week treatment intervals. The safety profile was similar in patients with PCV and the overall PULSAR nAMD population.
Dr. Singer concluded his talk with an exclusive snapshot of the 96-week results of the overall PULSAR trial which showed 87% randomized to 8q12 were able to be extended to 12 weeks or longer during this timeframe and 78% randomized to 8q16 were able to be extended to 16 weeks or longer. Twenty five percent and 31% in the 8q12 and 8q16 groups, respectively, were able to be extended to 24 weeks.
A lively discussion followed Dr. Singer’s presentation. Moderator, Dr. Mark Johnson, raised the point that the study design did not allow those in the 2q8 week to be extended beyond 8 weeks. We know, from in-clinic experience, that several patients can be extended beyond 8 weeks with 2 mg intravitreal aflibercept as well. In his rebuttal, Dr. Singer acknowledged this reality and noted that the PULSAR Trial organizers have considered this concern and are working to expand what is considered standard of care in future trials.