Aflibercept 8mg noninferior to Aflibercept 2mg in nAMD Treatment: PULSAR Trial
New research revealed that aflibercept 8 mg was non-inferior to aflibercept 2 mg and provided more significant therapeutic benefit, prolonged injection interval, and similar safety compared to aflibercept 2 mg. The study was presented at the 2023 ARVO Annual Meeting and published in the journal Investigative Ophthalmology and Visual Science.
Neovascular age-related macular degeneration, also known as exudative or wet AMD is a common, progressive retinal degenerative macular disease that is characterized by neovascularization of the choroid, mainly affecting the elderly population leading to gradual vision impairment. Anti-VEGF is the main modality of the treatment of nAMD. Aflibercept, a 115 kDa completely human recombinant fusion protein that binds to VEGF-A, VEGF-B, and placental growth factor (PlGF), is made up of the immunoglobulin binding domains of VEGF receptors 1 and 2. Recent literature has shown that aflibercept 2mg can be used for naïve neovascular age-related macular degeneration (nAMD). Hence researchers conducted a trial to evaluate the efficacy and safety of intravitreal aflibercept 8 mg injection administered every 12 (8q12) or 16 weeks (8q16) for the management of treatment-naïve neovascular age-related macular degeneration (nAMD).
PULSAR trial is an ongoing, double-masked, 96-week, Phase 3 trial that recruited patients aged ≥50 years with nAMD. Participants were randomly assigned 1:1:1 to receive 8q12, 8q16, or 2q8 of aflibercept 8 mg injection and 2mg injection. The best-corrected visual acuity (BCVA) change from baseline and measured at Week 48 by a non-inferiority margin at four letters was considered as the primary endpoint. The key secondary endpoint was the proportion of patients with no intraretinal/subretinal fluid (IRF/SRF) in the central subfield at Week 16, and other secondary endpoints included safety. The proportion of patients with ≥12-week and 16-week treatment intervals through Week 48 was the Exploratory endpoint.
Results:
- Nearly 1009 patients with a mean±SD age of 74.5±8.4 years () were evaluated, of which there were 54.5% female.
- There were 335 in the 8q12 group, 338 in the 8q16 group, and 336 in the 2q8.
- Aflibercept 8 mg met the primary endpoint (8q12 vs. 2q8: p=0.0009; 8q16 vs. 2q8: p=0.0011).
- Observed mean (±SD) change from baseline (±SD) in BCVA at Week 48 was +6.7±12.6, +6.2±11.7, and +7.6±12.2 letters with 8q12, 8q16, and 2q8, respectively.
- In the 8q12 group, 79% of patients (n=316) maintained 12-week treatment intervals, and 77% of patients in the 8q16 group (n=312) maintained 16-week treatment intervals in Year 1.
- Overall, 83% (n=628) of patients receiving aflibercept 8 mg maintained ≥12-week treatment intervals in Year 1.
- Aflibercept 8 mg demonstrated superior drying versus aflibercept 2 mg at Week 16; 63% versus 52% of patients, respectively, had no IRF/SRF in the central subfield (p=0.0002).
- Aflibercept 8 mg had a similar safety profile to aflibercept 2 mg.
Thus, Aflibercept 8 mg was safe, and efficacious and was maintained by the patients for ≥12-week dosing, and 16-week dosing than Aflibercept 2 mg.
Further reading: Intravitreal aflibercept 8 mg injection in patients with neovascular age-related macular degeneration: 48-week results from the Phase 3 PULSAR trial. Invest. Ophthalmol. Vis. Sci. 2023;64(8):461.
