Aflibercept 8 mg for DME Dosed Every 12/16 Weeks: Comparable BCVA to Every-8-Week Dosing
Few injections lowers treatment burden and maintains safety profile.
(Image Credit: ©Aliaksandr Marko - Adobe.Stock.com)
Reviewed by Charles Wykoff, MD, PhD
Aflibercept 8 mg (Eylea, Regeneron Pharmaceuticals) dosed every 12 weeks and every 16 weeks in the 2-year phase 2/3 PHOTON Study achieved best-corrected visual acuity (BCVA) results that were non-inferior to aflibercept dosed every 8 weeks in patients with diabetic macular edema (DME). This resulted in a lower treatment burden of up to 6 fewer injections.
Charles Wykoff, MD, PhD, reported the 96-week results at the Euretina Congress, Amsterdam. He is from Retina Consultants of Texas, Houston.
Other topline findings were that through week 96, 89% of the patients treated with the 8-mg aflibercept dose maintained a dosing interval of 12 weeks or longer, with 44% of patients receiving the 8-mg dose at a 20-week or 24-week interval at week 96. Importantly, the safety of the 8-mg dose was comparable to the drug’s 2-mg dose over the course of the study.
Aflibercept is a fully human recombinant fusion protein that binds vascular endothelial growth factors (VEGF) A and B and placental growth factor; this activity inhibits activation of cognate VEGF receptors.
The 8-mg dose of aflibercept 8 mg delivered intravitreally both provides a 4-fold higher molar dose than aflibercept 2 mg in a 70-µL injection and improved functional and anatomic outcomes at dosing intervals of 12 weeks or longer in ongoing clinical trials of its effects against neovascular age-related macular degeneration, DME, and diabetic retinopathy.1,2
PHOTON Study
This was a multicenter, randomized, double-masked study in patients with DME who were randomized 1:2:1, respectively, to aflibercept 2 mg every 8 weeks in 167 patients after 5 initial monthly injections, aflibercept 8 mg every 12 weeks after 3 initial monthly injections in 328 patients, and aflibercept 8 mg every 16 weeks after 3 initial monthly injections in 163 patients.
The primary endpoint at 48 weeks was the mean change in the BCVA. An optional extension study after week 96 extended out to week 156. An average of more than 80% of patients in the 3 treatment arms completed the study at 96 weeks.
The primary endpoint, ie, the mean change in the BCVA at 96 weeks, showed the following letter increases, 8.8, 8.4, and 7.5, respectively, in the every-12-week dosing group, the every-8-week dosing group, and the every-16-week dosing group.
In addition, 89% of patients randomized to 8 mg aflibercept maintained dosing intervals of 12 weeks or longer, Wykoff reported. At the last assigned dosing interval at 96 weeks, 44% of patients randomized to 8 mg aflibercept had assigned dosing intervals of 20 weeks or longer.
The mean number of injections at 96 weeks were 13.8, 9.5, and 7.8, respectively, in the every-8 week, every-12-week, and every 16-week groups.
The increases in the BCVA were accompanied by decreases in the central retinal thickness. The mean changes were -155 microns, -185 microns, and -187 microns, respectively in the every-16-week, every 12-week, and every-8 week dosing groups.
Cataract, vitreous floaters, and conjunctival hemorrhages were the ocular adverse effects that developed in 5% or more of patients in any of the 3 arms. Ischemic optic neuropathy did not develop in any group over 96 weeks. Intraocular inflammation developed in 1.2% of patients in all groups. Increased intraocular pressure developed in 0.4% of all groups.
“While every trial has limitations, Aflibercept 8 mg has demonstrated impressive durability in the PHOTON Study, with great safety through 96 weeks. It is a welcome addition to our clinical armamentarium for optimizing visual and anatomic outcomes, while minimizing the treatment burden for our patients,” Wykoff concluded.
References:
Lanzetta P. Intravitreal aflibercept injection 8 mg for nAMD: results from the phase 3 PULSAR trial. Presented at the American Academy of Ophthalmology; September 30, 2022; Chicago, IL.
Brown DM. Intravitreal aflibercept injection 8 mg for DME: results from the phase 2/3 PHOTON trial. Presented at the American Academy of Ophthalmology; September 30, 2022; Chicago.
Charles Wykoff, MD, PhD
E: Charleswykoff@gmail.com
Wykoff is a consultant to Regeneron and Bayer.
