On this episode of Evidence Based Retina, Rishi P. Singh, MD, FASRS, is joined by David Eichenbaum, MD, FASRS, to discuss aflibercept 8mg (EYLEA HD, Regeneron) for macular edema following retinal vein occlusion (RVO) and conclusions from the QUASAR study (NCT05850520).
Dr. Eichenbaum is a partner and Director of Research at Retina Vitreous Associates of Florida. He also serves as a Volunteer Collaborative Associate Professor of Ophthalmology at the Morsani College of Medicine, University of South Florida.
QUASAR study fast facts
- Design: Patients were randomized into three groups to receive either:1
- Group 1: Aflibercept 8mg every 8 weeks following 3 initial monthly doses
- Group 2: Aflibercept 8mg every 8 weeks following 5 monthly doses
- Note: n=591 for these two groups
- Group 3: Aflibercept 2mg every 4 weeks (n=301)
- Study duration: 64 weeks
- Participants: 892 patients diagnosed with macular edema following RVO
- Primary endpoint: Mean change in best-corrected visual acuity (BCVA) from randomization through Week 36, measured via Early Treatment Diabetic Retinopathy Study (ETDRS) letter score
- Findings: The study met its primary endpoint at 36 weeks, wherein both aflibercept 8mg groups achieved non-inferior VA gains compared to the aflibercept 2mg group with fewer injections.1 These results were consistent across all studied RVO subtypes.
- A total of 88% of participants sustained an 8-week dosing regimen following the required 3 monthly doses, with 93% maintaining this regimen after completing 5 initial monthly doses.1
- Safety: Treatment-emergent adverse events occurred in ≥5% of all aflibercept 8mg patients, including increased ocular pressure (5%).1 The rate of intraocular inflammation (IOI) was 0.5% for aflibercept 8mg and 1.3% for aflibercept 2mg. One case of endophthalmitis and retinal vasculitis each was reported.
- Relevance: The FDA approved macular edema after RVO as a new indication for aflibercept 8mg and expanded dosing intervals based on data from QUASAR.2
Relevance of findings from QUASAR
While Dr. Eichenbaum’s practice was involved in the PULSAR (NCT04423718) and PHOTON (NCT04429503) trials, he was particularly excited to see the results of the QUASAR study because RVO pathogenesis is heavily mediated by vascular endothelial growth factor (VEGF).3 Due to the high load of VEGF found in RVO patients, a potent VEGF antagonist like aflibercept at a higher dose would likely be especially well-suited for RVO.
Case in point, after 3 initial monthly injections, patients in the aflibercept 8mg groups required an average of 6.1 injections at week 36 compared to 8.8 injections in the 2mg group.4 At Week 36, about 70% of patients had a last assigned dosing interval of every 12 weeks. Conversely, 25% of patients in the aflibercept 2 mg group still required monthly injections, compared with only 6% in the 8mg arms.4
Looking for an update on RVO treatments? Check out Advances in the Management of Retinal Vein Occlusion.
Identifying optimal RVO patients for aflibercept 8mg
Dr. Eichenbaum explained that the higher molar dosing of aflibercept provides a combination of improved drying and durability, with the potential for even longer extensions than have been seen in previous agents for RVO.
Consequently, he recommended clinicians consider aflibercept 8mg in the following patients:
- Those who can’t dry out completely on aflibercept 2mg or faricimab (especially now that the aflibercept label includes monthly dosing)
- Individuals who cannot extend past 6 or 7 weeks on aflibercept 2mg or on faricimab, with the goal of getting them to 8-, 9-, or 10-week injection intervals.
- Treatment-naive patients, since all patients want to achieve the longest extension intervals as quickly as possible between injections.
What’s next for aflibercept 8mg?
Now that aflibercept 8mg has been approved for RVO and with more flexible dosing, collecting and analyzing real-world data on outcomes and durability in RVO is critical to see how it performs generally and compares to faricimab.
Dr. Eicheinbaum noted that he is also looking forward to the convenience of having a prefilled syringe (PFS), although the availability of PFS is not a major factor when he recommends a treatment.
In terms of existing real-world safety data, he highlighted a recent study presented by Diana Do, MD, using the IRIS database to identify patients on aflibercept 8mg for neovascular age-related macular degeneration (nAMD). This analysis included over 10,000 eyes and revealed no new safety signals, aligning with previous clinical trial findings of both aflibercept 2mg and 8mg.5
What is the durability of aflibercept 8mg in other retinal diseases?
Aflibercept 8mg has already demonstrated exceptional durability in registration trials for DME and nAMD, with 16% of patients extended to 20 weeks and 27% extended to 24-week dosing intervals in DME, while 47% of patients were eligible for ≥20-week intervals and 28% for 24-week intervals in nAMD without loss of vision gains.6,7
Additionally, the ELARA (NCT06491914) clinical trial demonstrated that monthly dosing in prior-treated eyes with DME or nAMD provided beneficial and impactful improvements in both vision and reductions in retinal thickness.5
Conclusion
One key question that remains unanswered is whether faricimab or aflibercept 8mg is the superior second-generation anti-VEGF for drying or durability. Of note, there is no head-to-head comparative data in any disease state for these two drugs.
The differences may come down to patient factors as much as drug factors, but with the recent FDA approval of the RVO indication and more flexible dosing intervals for aflibercept 8mg, retina specialists now have even more treatment options for these patients.
