EYP-1901 vs Aflibercept for Age-Related Macular Degeneration

(wAMD Trial)

Recruiting at 74 trial locations

Overseen By Ramiro Ribeiro, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: EyePoint Pharmaceuticals, Inc.

Must be taking: Anti-VEGF injections

Disqualifiers: Subfoveal fibrosis, Atrophy, Scarring, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 56 weeks

400 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase 3 randomized, double -masked study comparing the efficacy of EYP-1901 against Aflibercept.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are already receiving anti-VEGF injections for your condition, you may need to continue them as part of the study.

What data supports the effectiveness of the drug Aflibercept for treating age-related macular degeneration?

Research shows that Aflibercept is effective in treating age-related macular degeneration, with studies reporting positive outcomes in visual improvement and reduced need for frequent injections. ^{1 2 3 4 5}

Is EYP-1901 or Aflibercept safe for humans?

Studies on aflibercept (also known as Eylea or Zaltrap) show it is generally safe for treating eye conditions like age-related macular degeneration and diabetic macular edema, with no major adverse events reported in the short term. ^{6 7 8 9 10}

How is the drug EYP-1901 (Aflibercept) unique for treating age-related macular degeneration?

EYP-1901 (Aflibercept) is unique because it acts as a decoy receptor for VEGF, a protein that promotes abnormal blood vessel growth in the eye, and it requires fewer injections compared to some other treatments, potentially reducing the treatment burden for patients. ^{9 11 12 13 14}

Eligibility Criteria

This trial is for individuals with wet Age-Related Macular Degeneration (wAMD), either new or previously treated. Participants must have a certain level of vision, measured by the ETDRS letter score, and if previously treated, they should have had at least two anti-VEGF injections in the past six months.

Inclusion Criteria

I've had at least 2 eye injections for wet AMD in the last 6 months.

My vision in the study eye ranges from 20/32 to 20/200 with correction.

I have been diagnosed with wet AMD in one eye, regardless of prior treatments.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either EYP-1901 or Aflibercept for the treatment of wet AMD

56 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Participants may continue to receive treatment for up to 2 years

Additional 48 weeks

Treatment Details

Interventions

• Aflibercept
• EYP-1901

Trial Overview The study compares EYP-1901 to Aflibercept over two years to see which is more effective for wAMD. It's a phase 3 trial where participants are randomly assigned treatments and neither they nor the researchers know who gets which treatment (double-masked).

Participant Groups

Group I: EYP-1901 2686 µg Experimental Treatment 1 Intervention

EYP-1901

Group II: Aflibercept Active Control 1 Intervention

Aflibercept is already approved in United States, European Union for the following indications:

Approved in United States as Eylea for:

• Neovascular (Wet) Age-Related Macular Degeneration (AMD)
• Macular Edema following Retinal Vein Occlusion (RVO)
• Diabetic Macular Edema (DME)
• Diabetic Retinopathy (DR)

Approved in European Union as Eylea for:

• Neovascular (Wet) Age-Related Macular Degeneration (AMD)
• Macular Edema following Retinal Vein Occlusion (RVO)
• Diabetic Macular Edema (DME)
• Diabetic Retinopathy (DR)

Approved in United States as Zaltrap for:

• Metastatic Colorectal Cancer

Who Is Running the Clinical Trial?

EyePoint Pharmaceuticals, Inc.

Lead Sponsor

Trials

19

Recruited

2,700+

Findings from Research

In a study of 28 patients with newly diagnosed wet age-related macular degeneration (ARMD), treatment with aflibercept showed significant efficacy, with 89.3% of eyes maintaining or improving visual acuity after one year.

The treatment was safe, with no recorded complications, and resulted in a substantial reduction in central retinal thickness, indicating effective management of the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ONE-YEAR FOLLOW-UP OUTCOMES OF TREATMENT OF WET AGE-RELATED MACULAR DEGENERATION WITH AFLIBERCEPT. Klimešová, YM., Penčák, M., Straňák, Z., et al.[2019]

In a study of 36 patients with neovascular age-related macular degeneration (AMD), aflibercept treatment resulted in a significant improvement in visual acuity, with a mean gain of nearly 16 letters after an average follow-up of 12 months.

The treatment was safe and effective, with 97.3% of patients maintaining their vision, and a decrease in central macular thickness, indicating a positive impact on the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The results of aflibercept therapy as a first line treatment of age-related macular degeneration. Unsal, E., Cubuk, MO.[2023]

In a study of 1027 treatment-naïve patients with neovascular age-related macular degeneration, both ranibizumab and aflibercept showed similar improvements in visual acuity after one year, indicating their comparable efficacy.

Patients treated with aflibercept required 15% fewer injections than those treated with ranibizumab, suggesting that aflibercept may offer a more convenient treatment regimen without compromising visual outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neovascular age-related macular degeneration treated with ranibizumab or aflibercept in the same large clinical setting: visual outcome and number of injections. Rasmussen, A., Sander, B., Larsen, M., et al.[2022]

In a study of 28 patients with refractory wet age-related macular degeneration, switching to high-dose aflibercept (4 mg every 4 weeks) led to a dry retina in an average of 3.8 months, demonstrating its efficacy in treating resistant cases.

The treatment resulted in significant reductions in retinal fluid and thickness, with 45% of patients experiencing improved vision, and importantly, no serious adverse events were reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HIGH-DOSE HIGH-FREQUENCY AFLIBERCEPT FOR RECALCITRANT NEOVASCULAR AGE-RELATED MACULAR DEGENERATION. You, QS., Gaber, R., Meshi, A., et al.[2019]

In a study of 26 patients with neovascular age-related macular degeneration (nv-AMD), intravitreal injections of aflibercept (Eylea) led to a significant improvement in visual acuity over 14 months, with 61.5% of eyes showing improvement and a mean visual acuity change from 0.26 to 0.14 LogMAR (P=0.02).

The treatment also resulted in a significant reduction in central macular thickness from 409μm to 229μm (P<0.02), and no adverse events were reported, indicating that aflibercept is a safe and effective option for treating naïve patients with nv-AMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal aflibercept (A-IVI) for the treatment of neovascular age-related macular degeneration (nv-AMD): one year experience. Papavasileiou, E., Zygoura, V., Richardson, T., et al.[2019]

A study involving 12 patients showed that a single intravitreal injection of ziv-aflibercept for treating choroidal neovascularization due to age-related macular degeneration was safe, with no serious ocular or systemic adverse events reported after 30 days.

While there was only a slight improvement in best-corrected visual acuity after treatment, the absence of significant side effects suggests that ziv-aflibercept could be a viable low-cost alternative for macular disease therapy, especially in resource-limited settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SHORT-TERM SAFETY PROFILE OF INTRAVITREAL ZIV-AFLIBERCEPT. Chhablani, J., Narayanan, R., Mathai, A., et al.[2022]

In a study of 60 patients receiving an average of 8.4 intravitreal injections of ziv-aflibercept over a mean follow-up of 9.2 months, significant improvements in best-corrected visual acuity (BCVA) and reductions in central macular thickness (CMT) were observed, indicating the treatment's efficacy for retinal disease.

The treatment was found to be safe, with no significant increases in intraocular pressure, no progression of lens opacities, and only one case of mild transient iritis, suggesting that repeated injections of ziv-aflibercept are well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of ziv-aflibercept in retinal diseases. Mansour, AM., Ashraf, M., Dedhia, CJ., et al.[2022]

In a study of 553 patients with diabetic macular edema treated with intravitreal aflibercept over 52 weeks, there was a significant improvement in vision-related quality of life, as measured by the NEI VFQ-25 total score, which increased by an average of +6.11 points.

The treatment also led to notable improvements in best-corrected visual acuity (BCVA) and a reduction in central retinal thickness (CRT), while the safety profile was consistent with known effects, with 53.6% of patients experiencing treatment-emergent adverse events, including a low incidence of serious ocular events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vision-Related Quality of Life in Patients with Diabetic Macular Edema Treated with Intravitreal Aflibercept: The AQUA Study. Garweg, JG., Stefanickova, J., Hoyng, C., et al.[2020]

A patient with exudative age-related macular degeneration showed significant improvement in visual acuity and reduction of fluid after receiving an intravitreal injection of ziv-aflibercept, indicating its efficacy in treating this condition.

The treatment was well-tolerated with no adverse events reported, demonstrating both short-term safety and effectiveness in managing neovascular macular degeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal injection of ziv-aflibercept in patient with refractory age-related macular degeneration. de Oliveira Dias, JR., Xavier, CO., Maia, A., et al.[2015]

In a study of 94 patients with diabetic macular edema (DME), intravitreal aflibercept injections significantly improved best-corrected visual acuity (BCVA) by an average of +7.4 letters after 36 months, with treatment-naive patients showing even greater improvement (+8.9 letters).

The treatment was found to be safe, with only mild, non-sight-threatening ocular adverse events reported, indicating that aflibercept is a viable option for managing DME in a real-life setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aflibercept for Diabetic Macular Edema in Real-Life Practice in GREece: Three-Year Outcomes of the ADMIRE Study. Chatziralli, I., Agapitou, C., Dimitriou, E., et al.[2023]

Aflibercept, a treatment for wet age-related macular degeneration, was found to be noninferior to ranibizumab in maintaining vision after one year, based on two pivotal phase III studies involving similar designs.

Patients treated with aflibercept required, on average, five fewer injections over 96 weeks compared to those receiving ranibizumab, while both treatments had similar safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aflibercept for intravitreal injection: in neovascular age-related macular degeneration. Frampton, JE.[2021]

A single intravitreal injection of ziv-aflibercept led to a significant reduction in the height of a treatment-resistant retinal pigment epithelial detachment (PED) in a 67-year-old woman, demonstrating its efficacy in managing neovascular age-related macular degeneration.

The treatment was well-tolerated with no signs of toxicity, suggesting that ziv-aflibercept could be a safe alternative for patients in regions where other treatments like aflibercept are unavailable or too expensive.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FLATTENING OF A TREATMENT-RESISTANT RETINAL PIGMENT EPITHELIAL DETACHMENT AFTER A SINGLE INTRAVITREAL INJECTION OF ZIV-AFLIBERCEPT. Yogi, R., Stewart, M., Chhablani, J.[2017]

Ziv-aflibercept, an analogue of aflibercept, has shown a similar safety profile to existing treatments for neovascular age-related macular degeneration (nAMD), effectively maintaining or improving best-corrected visual acuity (BCVA) and reducing retinal fluid and central foveal thickness (CFT).

Clinical trials indicate that ziv-aflibercept is also effective in treating other neovascular conditions like diabetic macular edema (DME) and retinal vein occlusion (RVO), but further randomized studies are necessary to confirm its efficacy specifically for nAMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal Ziv-Aflibercept: A Comprehensive Review. Barmas-Alamdari, D., D'Souza, HS., Kapoor, KG., et al.[2019]

Aflibercept, a recombinant fusion protein, effectively inhibits VEGF signaling and has been shown to significantly improve visual acuity in patients with macular edema due to central retinal vein occlusion (CRVO) when administered intravitreally at a dose of 2 mg monthly, as demonstrated in clinical trials with significant improvements over sham injections.

The treatment was generally well tolerated with minimal risk of systemic drug accumulation, making aflibercept a safe and effective option for managing CRVO-related macular edema, although optimal monitoring strategies for long-term efficacy still need further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal aflibercept (Eylea(®)): a review of its use in patients with macular oedema secondary to central retinal vein occlusion. Yang, LP., McKeage, K.[2021]

References

1. Czech Republic pubmed.ncbi.nlm.nih.gov

ONE-YEAR FOLLOW-UP OUTCOMES OF TREATMENT OF WET AGE-RELATED MACULAR DEGENERATION WITH AFLIBERCEPT. [2019]

2. India pubmed.ncbi.nlm.nih.gov

The results of aflibercept therapy as a first line treatment of age-related macular degeneration. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Neovascular age-related macular degeneration treated with ranibizumab or aflibercept in the same large clinical setting: visual outcome and number of injections. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

HIGH-DOSE HIGH-FREQUENCY AFLIBERCEPT FOR RECALCITRANT NEOVASCULAR AGE-RELATED MACULAR DEGENERATION. [2019]

5. Greece pubmed.ncbi.nlm.nih.gov

Intravitreal aflibercept (A-IVI) for the treatment of neovascular age-related macular degeneration (nv-AMD): one year experience. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

SHORT-TERM SAFETY PROFILE OF INTRAVITREAL ZIV-AFLIBERCEPT. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of ziv-aflibercept in retinal diseases. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Vision-Related Quality of Life in Patients with Diabetic Macular Edema Treated with Intravitreal Aflibercept: The AQUA Study. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Intravitreal injection of ziv-aflibercept in patient with refractory age-related macular degeneration. [2015]

10. England pubmed.ncbi.nlm.nih.gov

Aflibercept for Diabetic Macular Edema in Real-Life Practice in GREece: Three-Year Outcomes of the ADMIRE Study. [2023]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Aflibercept for intravitreal injection: in neovascular age-related macular degeneration. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

FLATTENING OF A TREATMENT-RESISTANT RETINAL PIGMENT EPITHELIAL DETACHMENT AFTER A SINGLE INTRAVITREAL INJECTION OF ZIV-AFLIBERCEPT. [2017]

13. England pubmed.ncbi.nlm.nih.gov

Intravitreal Ziv-Aflibercept: A Comprehensive Review. [2019]

14. New Zealand pubmed.ncbi.nlm.nih.gov

Intravitreal aflibercept (Eylea(®)): a review of its use in patients with macular oedema secondary to central retinal vein occlusion. [2021]