The updated PULSAR results support aflibercept 8 mg as a treatment option for nAMD.Updated results from the phase III PULSAR trial show that intravitreal (IVT) aflibercept 8 mg, when administered at extended dosing intervals of up to 20 weeks, led to visual gains and anatomic improvements comparable to the 2-mg dose, with no new safety concerns over 96 weeks, in treatment-naïve individuals with neovascular age-related macular degeneration (nAMD).
“Consistent with the week (W)48 results, there were comparable best-corrected visual acuity (BCVA) gains … with aflibercept 8 mg (with extended dosing intervals) and 2 mg, with aflibercept 8 mg Q12W and Q16W remaining above the predefined noninferiority margin compared with aflibercept 2 mg Q8W,” the researchers said.
A total of 1,009 participants were randomized 1:1:1 to receive aflibercept 8 mg Q12W (group 1), 8 mg Q16W (group 2), or 2 mg Q8W (group 3). Patients who completed W96 in groups 1, 2, and 3 received a mean of 9.7, 8.2, and 12.8 active injections, respectively, through W96. [Ophthalmology 2026;133:39-50]
Efficacy, durability
At W96, the least-squares mean (LSM) changes in BCVA from baseline in groups 1, 2, and 3 were 5.6, 5.5, and 6.6 letters, respectively. For central retinal thickness, the corresponding LSM changes were -152, -148.8, and -146.8 μm.
Seventy-five percent of group 1 patients maintained their randomized dosing interval, and 70 percent of those in group 2 were qualified for further dosing interval extension through W96.
“Collectively, [these results show] that aflibercept 8 mg [can] provide sustained disease control in nAMD as defined by the interrelated goals of maintaining vision gains, rapid and resilient fluid control without clinically meaningful fluctuation, and both with extended treatment intervals in a substantial proportion of patients,” the researchers said.
Safety outcomes
Approximately half of the overall cohort had ocular treatment-emergent adverse events (TEAEs) in the study eye through W96, the most common being cataract (9.6–10.1 percent) and reduced visual acuity (6.3–7.1 percent).
Twenty-four patients had serious ocular TEAEs in the study eye. One serious ocular TEAE (angle-closure glaucoma [ACG]) was reported in a group 2 patient with a medical history of ACG in the study eye, and it was considered treatment-related. This was resolved, and the patient continued to receive treatment through the end of the trial without recurrence.
The rates of intraocular inflammation events were low across treatment groups (0.9–2.1 percent), and all but one (severe case of endophthalmitis in group 3) were mild-to-moderate in severity.
The rates of increased intraocular pressure events were comparable across groups (3–3.6 percent), as were the rates of non-ocular TEAEs (73.1–76.5 percent), serious TEAEs (18.9–21.8 percent), arterial thromboembolic events (1.5–3.3 percent), and hypertension events (8–8.3 percent).
The death rates were also similar and low (2.1–3.6 percent), and none were deemed treatment-related.
Reduced treatment burden
Aflibercept 2 mg is approved for the treatment of nAMD in several countries. [Lancet 2018;392:1147-1159] “To address the need to reduce treatment burden while maintaining visual benefits, an 8-mg formulation was developed to enable the IVT delivery of a four-times higher molar dose compared with the 2-mg formulation,” the researchers said. [JAMA Ophthalmol 2023;141:834-842]
These results support the previously reported W48 results and show that dosing intervals for aflibercept 8 mg can be extended to 24 weeks, providing strong support for the potential of this treatment to reduce treatment burden. [Lancet 2024;403:1141-1152]
The results were achieved with up to five fewer injections in group 2 than in group 3. “The less frequent dosing required with aflibercept 8 mg, compared with other agents, may reduce treatment burden, potentially increasing patient adherence and improving treatment outcomes,” the researchers said.