Regeneron Pharmaceuticals, Inc. announced top-line, two-year data from the PHOTON trial assessing aflibercept 8 mg for diabetic macular edema (DME).
Give me some details on aflibercept first.
Aflibercept is in a medication class of vascular endothelial growth factor A (VEGF-A) and placental growth factor (PIGF) antagonists that stops the growth of abnormal blood vessels and leakage in the eyes in patients diagnosed with retinal diseases.
And aflibercept 8 mg?
The high-dose drug is in joint development with Regeneron and Bayer AG; Regeneron owns exclusive rights to both Eylea (aflibercept) and aflibercept 8 mg in the United States, while Bayer has licensed the exclusive marketing rights outside of the country.
To note, both companies are currently equally splitting sales profits from Eylea and will follow suit for any future sales of aflibercept 8 mg (pending regulatory approval).
Tell me more.
A Biologics License Application (BLA) for the high-dose drug was accepted and given priority review by the FDA in February 2023 for DME, wet age-related macular degeneration (wAMD), and diabetic retinopathy (DR).
And, most recently, the FDA sent a complete response letter (CRL) to Regeneron that stated the agency would not approve the BLA. Read more about that here.
How does 8 mg aflibercept compare to Eylea?
Both medications are intravitreal injections of aflibercept formulations.
However, Eylea is a 2 mg aflibercept dosage prescription medicine and FDA approved for:
- wAMD
- Macular edema following retinal vein occlusion (RVO)
- DME
- DR
- Retinopathy of prematurity (ROP) in infants
Now talk about this trial.
Launched in 2020, the randomized, double-masked, active-controlled phase 2/3 PHOTON study (NCT04429503) randomized 658 patients with DME to receive either:
- Aflibercept 8 mg for 12 weeks (n = 328) (after three initial monthly doses)
- Aflibercept 8 mg for 16 weeks (n = 163) (after three initial monthly doses)
- Eylea for 8 weeks (n = 167) (after five initial monthly doses)
And the goal?
The primary endpoint was to determine if 12 or 16-week intervals of aflibercept provides non-inferior best-corrected visual acuity (BCVA) compared to aflibercept dosed in 8-week intervals.
What were the initial results?
The study reported positive data and met its primary endpoint.
Additionally, 91% and 89% of patients treated with aflibercept 8 mg were able to maintain their 12- and 16-week dosing regimens, respectively, through 48 weeks.
And what is this 2-year data showing?
According to Regeneron, a majority of aflibercept 8 mg patients maintained or further extended the 12- and 16-week dosing intervals through the 2-year period
Give me some numbers.
Two-year dosing interval maintenance included:
- 89% for ≥12 weeks (vs 93% at 48 weeks)
- 83% for ≥16 weeks (vs 89% at 48 weeks)
Any other dosing intervals?
Actually, yes … a reported 43% of aflibercept 8 mg patients met the study criteria for ≥20-week dosing intervals by week 96, including 16% and 27% who were eligible for 20- and 24-week dosing intervals, respectively.
Adverse events?
Ocular treatment adverse events (TAEs) were reported in ≥5% of patients among all treatment groups. These included (in decreasing frequency):
- Cataract
- Vitreous floaters
- Conjunctival hemorrhage
There were no reported cases of retinal vasculitis, occlusive retinitis, or endophthalmitis.
How do these findings compare to Eylea’s clinical data?
The safety of aflibercept 8 mg was demonstrated as similar to Eylea for DME through 2 years and visual gains were consistent with 1-year data.
So what does this mean?
“The aflibercept 8 mg clinical trial program is the first to demonstrate the high-dose drug’s ability to immediately treat DME patients with 12- or 16-week dosing after their initial monthly doses as well as experience lasting vision control, according to George D. Yancopoulos, MD, PhD, Board Co-Chair, President and CSO at Regeneron, and a principal inventor of Eylea.
What else to know?
According to Clinical Trials.gov, the PHOTON study is slated to conclude in June 2024.
Additionally, Regeneron expects to release 2-year data from the pivotal PULSAR trial (NCT04423718) on aflibercept 8 mg for wet AMD by Q3 2023.