Regeneron Pharmaceuticals, Inc. announced positive, 2-year topline data from the pivotal PULSAR trial assessing the use of aflibercept 8 mg in patients diagnosed with wet age-related macular degeneration (AMD).
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 can stop 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 2 mg) 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).
Wait … didn’t the company just release data on this?
Not quite … aflibercept 8 mg is undergoing further evaluation in the phase 2/3 PHOTON study (NCT04429503) for the treatment of diabetic macular edema (DME).
See here for the positive, topline-data from that study (reported in June 2023).
I feel like there was other news recently...
Indeed there was! In June 2023, the FDA sent a complete response letter (CRL) to Regeneron that stated the agency would not approve the company’s submitted Biologics License Application for DME, wet AMD, and diabetic retinopathy (DR).
Read more about that here.
So how does 8 mg aflibercept compare to Eylea?
While both medications are intravitreal injections of aflibercept formulations, Eylea is a 2 mg aflibercept dosage prescription medicine and FDA approved for:
- Wet AMD
- Macular edema following retinal vein occlusion (RVO)
- DME
- DR
- Retinopathy of prematurity (ROP)
Now talk about this study.
Launched in 2020, the randomized, double-masked, active-controlled phase 3 PULSAR study (NCT04423718) randomized 1,011 patients with wet AMD to receive either:
- Group 1
- Eylea every 8 weeks (after three initial monthly doses) (n =336)
- Group 2
- Aflibercept 8 mg every 12 weeks (after three initial monthly doses) (n= 335)
- Group 3
- Aflibercept 8 mg every 16 weeks (after three initial monthly doses) (n = 338)
Anything special about the dosings?
Actually … in the first year, patients in the aflibercept 8 mg groups [2 and 3] may have their dosing intervals shortened down to an every 8-week interval if protocol-defined criteria for disease progression were observed. Intervals could not be extended until the second year of the study.
Patients in all EYLEA groups maintained a fixed 8-week dosing regimen throughout their participation in the trials.
And the goal?
The primary outcome measure was change in best-corrected visual acuity (BCVA), as measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score (at baseline and Week 48).
Secondary outcomes included:
- Change in BCVA as measured by ETDRS (at baseline and Week 60).
- Proportion of patients with no intraretinal fluid or subretinal fluid in the center subfield (at Week 48)
- Change in central subfield retinal thickness(at baseline to Week 48).
- Number of patients gaining at least 15 letters in BCVA (at baseline and Week 48).
See here for the complete list.
Before we get to this new data ... what did 1-year results show?
PULSAR met its primary endpoint, with aflibercept 8 mg-treated patients achieving clinically equivalent vision gains compared to Eylea.
Now these 2-year findings.
The study reported positive data—similar to 2-year data from the PHOTON trial—with the majority of patients treated with aflibercept 8 mg “ able to maintain or further extending their dosing interval,” Regeneron reported.
Give me some numbers.
For patients who completed the 2-year follow-up:
- 88% were on a ≥12-week dosing interval at the end of 2 years.
- 78% maintained ≥ 12-week doing intervals throughout the 2-year study period (vs 83% at 48 weeks)
- 70% maintained ≥16-week dosing intervals at the end of 2 years.
Any other dosing intervals?
Yup! A reported 71% of aflibercept 8 mg patients met the extension criteria for ≥20-week dosing intervals by week 96, including 47% and 28% who were eligible for 20- and 24-week dosing intervals, respectively.
Further, for those at the end of the 2-year period, 78% were eligible for ≥16-week dosing and 53% were eligible for ≥20-dosing week intervals.
Did any other retinal cases pop up?
Similar to PHOTON, there were no reported cases of retinal vasculitis, occlusive retinitis, or endophthalmitis among aflibercept 8 mg patients.
The rate of intraocular inflammation (IOI) was 1.3% for aflibercept 8 mg patients and 2.1% for Eylea-treated patients.
Adverse events?
Treatment-emergent adverse events (TEAEs) occurred in 1.8% (aflibercept 8 mg) and 3.3% (Eylea) of patients.
How do these findings compare to Eylea’s clinical data?
According to trial investigator Charles C. Wykoff, MD, PhD: “These data are consistent with the results from the PHOTON trial in (DME), with both trials demonstrating a consistent safety profile with substantially fewer treatments than Eylea.”
Significance?
Pending FDA approval, aflibercept 8 mg has the potential to be a new standard of care for DME and wet AMD, Wykoff stated.
What else to know?
According to Clinical Trials.gov, the PULSAR study is expected to conclude by August 2024.