Abstract
Purpose :
In PULSAR (NCT04423718), the primary endpoint of change from baseline in best-corrected visual acuity at Week 48 (non-inferiority margin at 4 letters) was met with intravitreal aflibercept 8 mg every 12 or 16 weeks (8q12 or 8q16) vs aflibercept 2 mg every 8 weeks (2q8). Here, we report safety and tolerability through Week 48.
Methods :
PULSAR is an ongoing, double-masked, 96-week, Phase 3 trial. Patients aged ≥50 years with treatment-naïve neovascular age-related macular degeneration (nAMD) were randomly assigned 1:1:1 to 8q12, 8q16 or 2q8, each after three initial monthly injections.
Results :
Of 1,009 patients (mean age 74.5 years) randomly assigned and treated (2q8: n=336; 8q12: n=335; 8q16: n=338), 11 (1.1%) discontinued with adverse events (AEs) as the primary reason. In the 2q8, 8q12 and 8q16 groups, 46/336 (13.7%), 34/335 (10.1%), and 32/338 patients (9.5%) had treatment-emergent (TE) non-ocular serious AEs, respectively; adjudicated Antiplatelet Trialists’ Collaboration (APTC) events occurred in 1.5%, 0.3%, and 0.6%, respectively. In total, 38.3% of patients experienced at least one TE ocular AE in the study eye (2q8: 130/336 [38.7%]; 8q12: 129/335 [38.5%]; 8q16: 127/338 patients [37.6%]); most common were reduced visual acuity (6.0%, 3.6%, 5.3% for 2q8, 8q12 and 8q16, respectively), cataracts (3.0%, 3.6%, and 3.6%, respectively), and retinal hemorrhage (4.2%, 3.3%, and 3.0%, respectively). Pre-injection intraocular pressure (IOP) values were similar to baseline at all timepoints through Week 48. The proportion of patients with pre- or post-dose IOP ≥35 mmHg was similar in 2q8, 8q12 and 8q16 groups (0.3%, 0.9%, and 0.3%, respectively). Seven patients had intraocular inflammation (IOI; 2q8: 0.6%; 8q12: 1.2%; 8q16: 0.3%), none discontinued and there were no cases of endophthalmitis or occlusive retinal vasculitis. In all groups, proportions of patients with TE anti-drug antibody (ADA)-positive status were very low and consistent with rates previously reported for aflibercept 2 mg.
Conclusions :
The safety profile of aflibercept 8 mg was similar to that of aflibercept 2 mg through Week 48 in patients with nAMD. Of note, rates of APTC events, IOI and TE ADA-positivity were very low; IOI was not associated with positive ADA status.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.