Switching to Aflibercept 8mg in Patients Showing Limited Response to Previous Treatment

Phase

Condition

Macular Degeneration

Geographic Atrophy

Treatment

Aflibercept 8mg

Clinical Study ID

NCT06683950

2024-07-002

Ages > 50
All Genders

Study Summary

The treatment landscape for neovascular AMD has evolved with various anti-VEGF agents since 2006. Ranibizumab initially led the way, but its limited efficacy in reducing retinal edema paved the way for aflibercept in 2011, which became globally popular for its effectiveness and safety. Yet, aflibercept did not fully meet all patients' needs. In 2019, brolucizumab showed promising anatomical results but had higher risks of inflammation, limiting its use. Faricimab, introduced in 2022, aimed for longer-lasting effects by targeting VEGF-A and angiopoietin 2. Though it required fewer injections, questions remain about its long-term efficacy compared to aflibercept.

Despite recent advancements, no agent has established itself as the new standard since aflibercept's introduction, leaving significant unmet needs. Aflibercept 8mg, approved in 2023, has shown promise by matching long-term visual outcomes of aflibercept 2mg with fewer injections and comparable safety. This study examines the effects of switching to aflibercept 8mg for patients with a limited response to previous treatments, addressing the potential for aflibercept 8mg to meet current needs more effectively and providing timely data for its global rollout.

Eligibility Criteria

Inclusion

Inclusion Criteria:

Willing, committed, and able to return for ALL clinic visits and complete all studyrelated procedures.
Able to read, (or, if unable to read due to visual impairment, be read to verbatimby the person administering the informed consent or a family member) understand andwilling to sign the informed consent form.
Signed informed consent
Patients aged 50 years or older
Patients diagnosed with neovascular AMD or PCV
Patients underwent faricimab or aflibercept 2mg injections with an inverval of 4 to 16 weeks
Patients who continued to show persistent subretinal fluid (SRF) or intraretinalfluid (IRF) despite receiving two consecutive faricimab or aflibercept 2mginjections at the same injection interval.
In cases where the central retinal thickness did not decrease by more than 50 μmduring two consecutive treatments prior to inclusion in the study
ETDRS BCVA letter score ≥25 letters (approximately 20/320 or better) in the studyeye

Exclusion

Exclusion Criteria:

Any prior ocular (in the study eye) or systemic treatment or surgery for neovascularAMD except dietary supplements or vitamins.
Significant media opacities, including cataract, in the study eye that mightinterfere with visual acuity, assessment of safety, or fundus photography.
Any concurrent ocular condition in the study eye which, in the opinion of theinvestigator, could either increase the risk to the patient beyond what is to beexpected from standard procedures of intraocular injection, or which otherwise mayinterfere with the injection procedure or with evaluation of efficacy or safety.
Any ocular or periocular infection within the last 2 weeks prior to Screening ineither eye.
Any history of uveitis in either eye.
Presence of definite chorioretional anastomosis
Scar or fibrosis, making up > 50% of total lesion in the study eye.
Scar, fibrosis, or atrophy involving the center of the fovea in the study eye.
Presence of retinal pigment epithelial tears or rips involving the macula in thestudy eye.
History or clinical evidence of diabetic retinopathy, diabetic macular edema or anyother vascular disease affecting the retina, other than AMD, in either eye.
Any concurrent intraocular condition in the study eye (e.g. cataract) that, in theopinion of the investigator, could require either medical or surgical interventionduring the 76 week study period.
Prior vitrectomy in the study eye
Any history of macular hole of stage 2 and above in the study eye.
Any intraocular or periocular surgery within 3 months of Day 1 on the study eye,except lid surgery, which may not have taken place within 1 month of day 1, as longas its unlikely to interfere with the injection.
Prior trabeculectomy or other filtration surgery in the study eye.
Uncontrolled glaucoma (defined as intraocular pressure ≥ 25 mmHg despite treatmentwith antiglaucoma medication) in the study eye.
Active intraocular inflammation in either eye.
Active ocular or periocular infection in either eye.
Aphakia or pseudophakia with absence of posterior capsule (unless it occurred as aresult of a yttrium aluminum garnet [YAG] posterior capsulotomy) in the study eye.
History of corneal transplant or corneal dystrophy in the study eye.

Study Design

Aflibercept 8mg

October 21, 2024

May 31, 2026

Study Description

The treatment of neovascular AMD with anti-VEGF agents has evolved significantly. Introduced in 2006, ranibizumab heralded the era of anti-VEGF therapies but had limitations in duration and effectiveness in reducing retinal edema. To overcome these issues, aflibercept was introduced in 2011 and has been recognized for its superior efficacy and safety,1 becoming the most widely used drug globally. However, aflibercept also showed limited response in some patients, and the duration of its effectiveness was not always satisfactory.

Brolucizumab, introduced in 2019, demonstrated excellent anatomical outcomes but had a relatively high incidence of intraocular inflammation, ranging from 3 to 10%, preventing it from becoming a widely accepted standard treatment. The most recent, faricimab, introduced in 2022, was developed to inhibit not only VEGF-A but also angiopoietin 2, aiming for longer-lasting effects. In the TENAYA/LUCERNE clinical trials comparing its efficacy and safety with aflibercept, faricimab showed similar effects with fewer injections. However, due to differences in the treatment protocols between the aflibercept and faricimab groups, there remains a question about whether faricimab truly offers a longer duration of effect.

In conclusion, despite the introduction of brolucizumab and faricimab over the long span of 13 years since aflibercept was first introduced, these drugs have struggled to establish themselves as the new standard agents, especially when considering their overall efficacy and safety. Consequently, there has been a significant accumulation of unmet needs in the clinical treatment landscape over this extended period.

Aflibercept 8mg, the most recently FDA-approved agent in 2023, demonstrated not only superior initial anatomical effects compared to aflibercept 2mg in the PULSAR study, but also achieved similar long-term visual outcomes with fewer injections. Furthermore, it exhibited excellent safety, comparable to that of aflibercept 2mg. Based on these outcomes, many experts anticipate that aflibercept 8mg will become the new standard agent in the treatment of neovascular AMD, officially succeeding aflibercept 2mg.

Excluding aflibercept 2mg, faricimab could be considered the strongest contender for establishing aflibercept 8mg as the new standard. This is attributed to faricimab demonstrating satisfactory effects and excellent safety in clinical trials, as well as in subsequent real-world studies. Currently, there are no head-to-head clinical trials comparing these two drugs, and even if such trials are planned, it would take a considerable amount of time to ascertain the results. However, there is a simpler method to compare the effectiveness of a new agent against existing ones, which involves evaluating the effects of switching treatment in patients who have shown limited response to the current medication. In fact, such switching to new pharmaceutical agents after their introduction is widely practiced in clinical settings.10 Historically, the excellent efficacy observed when switching from ranibizumab to aflibercept 2mg played a significant role in the widespread adoption of aflibercept 2mg.

In this study, investigators aimed to evaluate the effects of switching to aflibercept 8mg in patients who have shown limited response to previous faricimab or aflibercept 2mg treatment. To the best of our knowledge, no such study has been reported in the English literature so far. This study not only has the potential to highlight the extended duration of action of aflibercept 8mg, but also holds significant importance in addressing the current unmet needs in the treatment of neovascular AMD. Additionally, by completing the study in a short period, investigators can contribute to generating timely data that aligns with the global introduction of aflibercept 8mg.

Connect with a study center

Kim's Eye Hospital
Seoul, 150-034
Korea, Republic of
Active - Recruiting

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.