In this episode of Evidence Based Retina, Rishi P. Singh, MD, FASRS is joined by Diana Do, MD, to discuss the real-world use of aflibercept 8mg (EYLEA HD, Regeneron Pharmaceuticals) as reported in the IRIS Registry, a clinical database managed by the American Academy of Ophthalmology (AAO).
Dr. Do is the Vice Chair of Clinical Affairs and Professor of Ophthalmology at the Byers Eye Institute at Stanford University in California.
Aflibercept 8mg fast facts
- Aflibercept is a vascular endothelial growth factor (VEGF) inhibitor that prevents the growth of abnormal blood vessels associated with retinal diseases.1
- Aflibercept 8mg (marketed as EYELEA HD) was developed by Regeneron and Bayer AG (with exclusive rights owned by Regeneron in the US) as a high-dose drug administered by intravitreal injection.2,3
- It was approved by the FDA in August 2023 for use in patients with wet age-related macular degeneration (AMD), diabetic macular edema (DME), and diabetic retinopathy (DR).2,3
- Aflibercept 8mg is four times the molar dose of aflibercept 2mg (marketed as EYELEA) which gained FDA approval to treat the above conditions in 2019.4
- Safety and efficacy was determined via clinical trial data from the PULSAR study for wAMD and the PHOTON study for DME.5,6,7,8
- Recommended use of aflibercept 8mg is 3 initial monthly doses followed by:
- 8mg every 8 to 16 weeks (2 to 4 months) for wet AMD and DME
- 8mg every 8 to 12 weeks (2 to 3 months) for DR
Real-world data on aflibercept 8mg from the IRIS Registry
Both the PULSAR and PHOTON studies used specific dosing regimens designed for testing durability and drug approval. However, real-world use often varies based on individual patient needs.
Dr. Do shares promising data on the real-world outcomes of aflibercept 8mg treatment by analyzing patient populations in the IRIS Registry.
They primarily looked at two populations:
- Treatment-naive patients who had not received any prior anti-VEGF agents
- Treatment-experienced patients eligible to receive other medicines for either wet AMD or DME
Dr. Do says they wanted to assess how these patients did when they started aflibercept 8mg compared to at least a 1-year follow-up period to see how retina specialists utilize it in their clinics every day. They identified over 1,300 treatment-naive wet AMD eyes and nearly 400 treatment-experienced DME eyes.
The majority received the three initial monthly loading doses of aflibercept 8mg. Drs. Rishi and Do agreed that while there is value in loading doses, many clinicians have adopted a “treat to dry” approach individualized for each patient because some may still have very active edema. However, three loading doses is optimal.
Check out the Glance story FDA approves expanded EYLEA HD dosing intervals for a recent update on aflibercept 8mg.
Findings on aflibercept 8mg for wet AMD and DME
The IRIS Registry data revealed that for treatment-naive patients with wet AMD, when vision was 20/50 or better they were more likely to gain at least 4 letters in vision. Importantly, 6 months following the first injection, the patients were able to extend their dosing intervals to 12 weeks.
Dr. Rishi remarks that AMD patients who receive aflibercept 2mg would never see an extension at that interval. Given that aflibercept 8mg is four times the molar dose of aflibercept 2mg, Dr. Do says it’s reasonable that the higher dose should extend the action of the drug inside the eye.
In treatment-naive DME patients, Dr. Do found a similar outcome. Patients gained almost 5 letters in vision and were able to extend their dosing intervals to at least 12 weeks at 6 months. These findings are promising given that treatment for DME often has restrictions on therapeutic options.
There were no new safety signals found in the IRIS Registry data, and aflibercept 8mg appears comparable to aflibercept 2mg in terms of safety.
What’s next for aflibercept 8mg?
Retinal vein occlusion (RVO) is often difficult to treat because those patients have the highest VEGF load.9 Treatment requires multiple visits, and Dr. Rishi says that if a patient misses a visit or two, they might end up with significant retinal thickness increases and drops in visual acuity.
Recently, Dr. Rishi discussed the results of the QUASAR study with Dr. David Eichenbaum and the expanded indications of aflibercept 8mg with FDA approval for macular edema after RVO.10,11
One of the challenges with treating wet AMD and DME is that without adequate drying, the dosing interval cannot be extended. Dr. Do shares promising results from the ELARA study which indicate that aflibercept 8mg can be used to treat every 4 weeks if necessary.12
Patients with a lot of disease activity may benefit from this shorter interval, even briefly, with potential to extend the interval slowly later on.
This article was written by Mariel Mohns, MS, based on the recorded video conversation between Drs. Rishi and Do.
