Lowering Treatment Burden and Maintaining Vision Gains with Aflibercept

The introduction of anti-vascular endothelial growth factor (anti-VEGF) therapy revolutionized the management and treatment of exudative retinal diseases — and over the past decade the evolution has continued. In 2011, aflibercept was FDA approved to treat neovascular age-related macular degeneration (nAMD). Since then, its commercial use has increased along with its efficacy in achieving meaningful vision gains across indications, including diabetic macular edema (DME) and retinal vein occlusion (RVO), among others.

To share the latest updates and best practices in managing and treating exudative retinal disease, experts will convene during a Bayer-sponsored symposia at the 22nd European Society of Retina Specialists Congress (EURETINA 2022) in Hamburg, Germany.

Below are preview of some of the highlights…

Ten Years of Delivering Outcomes that Matter

To see how far we’ve come, sometimes we need to look back — so, Prof. Focke Ziemssen of Leipzig University, Germany, will present with a background on aflibercept during his presentation entitled A Decade Long Legacy: From Clinical Trials to the Real World.

According to Prof. Ziemssen, aflibercept has transformed the management of exudative retinal disease — both in the approach to clinic management and patient outcomes — and real world outcomes have been similar to those in clinical trials. He says that a key component of the treatment’s efficacy can also be attributed to the proactive treat-and-extend (T&E) dosing regimen, which has shown to maintain vision gains while reducing the treatment burden through interval extensions up to 16 weeks. Not only that, Prof. Ziemssen will share that aflibercept has a well- established safety profile with more than eight million patient-years of exposure.

Looking Behind the Molecule

To understand how aflibercept works, it’s crucial to understand the science behind it. During his presentation, entitled Aflibercept: Behind the Molecule, Prof. Richard Gale of York Teaching Hospital NHS Foundation Trust, United Kingdom, will dissect the different mechanisms at play and how those contribute to the drug’s efficacy. He explains that VEGFR-1 and VEGFR-2 play a critical role in angiogenesis; excessive activation of VEGFR-1 and VEGFR-2 by ligands VEGF-A and PlGF activates three pathways involved in pathogenesis: inflammation, neovascularization, and retinal vascular leakage and edema.

Aflibercept is a multi-targeted fusion protein, incorporating domains from two VEGFRs for tight binding of VEGF-A and PlGF, blocking all VEGFR-1 ligands including PlGF, and the key VEGFR-2 ligand VEGF-A. This means aflibercept has the highest binding affinity for VEGF and the longest half-life when compared with other anti-VEGFs.

Continuing the momentum gained from positive patient outcomes and research, Prof. Nicole Eter, University of Münster, Germany, will share her insight during her talk entitled A Vision for the Future: What do the Next 10 Years Hold? According to her, there are three top spots to watch — those are novel anti- VEGF formulations, home monitoring, and cell and gene therapies. Prof. Eter says that previous targeting of novel pathways has failed to deliver additional functional benefits over currently available anti-VEGF agents in multiple trials, including those that target the Ang-2 pathway. In this example, she referred to the FDA approval package for faricimab: Patients treated with faricimab q12 experienced large central subfield thickness (CST) fluctuations and lost vision over time in TENAYA and LUCERNE, as did patients treated with faricimab q8 in TENAYA.

Further, whether a higher dose of the anti-VEGF may increase duration of VEGF suppression, and therefore allow for a reduced treatment burden, is currently evaluated in phase III studies of aflibercept 8 mg (increased from 2 mg) in nAMD and DME.

Patient Outcomes Across Indications

Experts will highlight patient cases across four indications, including nAMD, DME, RVO and polypoidal choroidal vasculopathy (PCV).

Prof. Justus G. Garweg, Berner Augenklinik, University of Bern, Switzerland, will share his experience during his presentation, entitled Exploring Patient Cases in DME. He says that a proactive, individualized approach to treatment with aflibercept is well suited to patients with DME. Further, aflibercept T&E regimen can achieve meaningful vision gains with extended intervals of ≥12 weeks in patients with DME — and this is especially important for patients who may have difficulty making frequent visits to the clinic.

During his presentation entitled Exploring Patient Cases in nAMD, Prof. Varun Chaudhary of McMaster University, Canada, will share details from a case of an 81-year-old patient with nAMD and 20/200 visual acuity (VA) in her right eye. The patient received monthly anti-VEGF for six months and asked to stop treatment; she could not sustain the monthly visits and said her vision wasn’t improving. Prof. Chaudhary says this is when he switched her to aflibercept — and under T&E, not only did her vision improve, her treatment intervals were proactively extended up to 16 weeks in her first year of treatment.

Next, Professor Gemmy Cheung of Singapore National Eye Centre, Singapore, will share her experience during her talk entitled Exploring Patient Cases in PCV. A key takeaway? She says that unlike other anti-VEGF agents in PCV — which may require concurrent treatment with photodynamic therapy to maximize VA gains — aflibercept q16 monotherapy reduces treatment burden with favorable long-term vision gains.

Finally, Exploring Patient Cases in RVO will be presented by Prof. Sobha Sivaprasad of Moorfields Eye Hospital, United Kingdom. She will share pearls from patient cases backed by studies, including the potential for a reduced treatment burden when compared with other anti-VEGF agents for patients with CRVO (LEAVO study). Meanwhile, Prof. Sivaprasad says that in CENTERA, patients treated with aflibercept T&E for macular edema secondary to CRVO gained an average of four lines of vision over 76 weeks.

The Future and Next Level in Patient Care

It’s clear that in the past 20 years, there has been major progress in surgery, imaging and therapies for managing retinal disease. However, there is still much work to be done — including access to diagnosis and treatment, along with increasing the understanding of disease mechanisms and advanced cell death.

Discussing some of these innovations will be Prof. Paolo Lanzetta (University of Udine, Italy) and Prof. Francine Behar-Cohen (Paris Descartes University, France) during their respective presentations on Innovating Treatments: Novel Approaches with Aflibercept and Treating the Currently Incurable: What is Coming Next? Among the highlights: There are a number of potential therapeutic targets under investigation to meet unmet needs in retinal disease. For example, targeting of the nitric oxide (NO) pathway using a novel oral formulation is currently under investigation in NEON-NPDR for the treatment of non-proliferative diabetic retinopathy. Researchers are also looking toward the future with aflibercept: The phase II CANDELA study has assessed the safety profile of aflibercept 8 mg and experts are optimistic about the data.

Additionally, with the aim of restoring vision after cell death, cell therapies aim to replace degenerative cells and/or supplement trophic factors to restore vision using stem/progenitor cells for their abilities of self-renewal and multidirectional differentiation. They noted that preclinical studies have shown promising results and early phase trials for the treatment of retinal degeneration are ongoing. Bayer is also involved in a collaboration investigating next-generation cell therapies for AMD and inherited retinal diseases.

But it’s not just our understanding of disease or continued innovations in treatments that will contribute to improving patient outcomes — technology can help, too. In particular, home monitoring has the potential to improve timing of intervention and therefore preserve vision – thereby reducing treatment burden, as Prof. Chaudhary will discuss during the presentation on Optimizing Treatment Outcomes Through Technological Innovation. Some of these tools are already available, and others may be available soon, including smartphone applications, at-home medical devices, handheld non-mydriatic fundus cameras, preferential hyperacuity perimetry devices, and home OCT devices.

The final speaker, Prof. Anat Loewenstein of Tel Aviv Medical Center, Israel, will remind delegates of the importance of education and collaboration during her talk, Improving Patient Care Through Holistic Disease Understanding. She says that ongoing initiatives supported by Bayer are striving to advance clinical knowledge and create a network of worldwide expertise; some of these initiatives include The Global Retinal Network Program and Vision Academy, among others.

All in all, it’s refreshing to have such a comprehensive overview — backed by clinical and real-world studies — that illustrate the progress made in managing exudative retinal diseases. With aflibercept T&E, it’s clear that patient outcomes are improving while their treatment burden is being reduced. And in the future, more advances promise even greater returns.

Editor’s Note: This is a preview of the Bayer symposia held at the recent EURETINA Congress (September 1-4, 2022) held in Hamburg, Germany. Writing for this article was based on materials provided by Bayer. This article was first published in PIE magazine issue 23.