Real-world utilization and initial experience with aflibercept-ayyh (PAVBLU(R)) for retinal disorders in United States retina practices: A descriptive retrospective analysis

This retrospective real-world analysis of 1,000 eyes treated with the aflibercept biosimilar aflibercept-ayyh (PAVBLU) in US retina practices demonstrated stable visual acuity in previously treated patients, improved vision in treatment-naive patients, and a safety profile consistent with the reference drug, supporting its use as an effective alternative for retinal disorders.

The Gist

🧐 The Big Picture: What is this study about?

Imagine your eye's retina is like a garden. Sometimes, this garden gets overgrown with weeds (diseases like macular degeneration or diabetic retinopathy) that choke the plants and ruin the view.

For years, doctors have used a special "weed killer" called Aflibercept (brand name EYLEA) to stop these weeds from growing. It works so well that it's the standard tool for gardeners (doctors) everywhere.

Recently, a new version of this weed killer arrived, called Aflibercept-ayyh (brand name PAVBLU). Think of this as a generic brand or a "knock-off" version of the famous name-brand tool. It's made by a different company (Amgen), but it is designed to be a perfect twin to the original.

The Question: Does this new, cheaper twin work just as well as the famous original in the real world, not just in a controlled lab?

The Answer: Yes. This study looked at 1,000 real-life gardens (eyes) and found that the new tool works exactly like the old one. It keeps the garden looking good, and it doesn't cause any new, weird problems.

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🔍 How Did They Check? (The Method)

The researchers didn't run a fake experiment in a lab. Instead, they acted like detectives reviewing old case files.

• The Data: They looked at the medical records of 1,000 eyes from patients across the United States who started using the new drug (PAVBLU) between late 2024 and late 2025.
• The Two Groups: They split the patients into two teams:
  1. The Switchers (91%): These patients were already using the original weed killer (or another brand) and decided to switch to the new one.
  2. The Newbies (9%): These patients had never used any weed killer before and started fresh with the new drug.

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📊 What Did They Find? (The Results)

1. The "Switchers" (People changing brands)

Imagine you have been driving a Toyota for 10 years. You decide to switch to a Honda that is built exactly the same way.

• The Result: When these patients switched to the new drug, their vision stayed exactly the same. They didn't get worse, and they didn't get significantly better.
• Why this is good: In the world of eye diseases, "staying the same" is a huge victory. It means the new drug is just as good at holding the line as the old one. It didn't cause a crash in vision quality.

2. The "Newbies" (People starting fresh)

Imagine a garden that has never been treated before. The weeds are everywhere.

• The Result: When these patients started using the new drug, their vision got better.
• Why this is good: It proves the drug is powerful enough to clear up the problem when used from the very beginning.

3. The Safety Check (Did anything go wrong?)

Every time you use a strong chemical, you worry about side effects. The researchers looked for "Special Interest Accidents" (like infections or bleeding in the eye).

• The Result: Out of 3,730 injections (that's a lot of shots!), there were only two tiny incidents of eye inflammation (iritis).
• The Analogy: If you drove 3,730 cars and only two had a flat tire, that's a very safe car. Both of those inflammation cases were minor, treated easily with eye drops, and went away completely. No one went blind, and no one got a serious infection.

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💡 The "So What?" (The Conclusion)

Think of the original drug (EYLEA) as a famous, expensive designer handbag. The new drug (PAVBLU) is the high-quality, identical-looking generic version.

This study confirms that:

1. The Generic is Real: It works just like the designer brand.
2. No Surprises: It doesn't have any hidden "bugs" or dangerous side effects that the original didn't already have.
3. Good for Everyone: Whether you are switching from another drug or starting fresh, this new option is a safe and effective choice.

In short: Doctors and patients can feel confident using this new, more affordable version of the drug. It's a win for the healthcare system because it offers more options without sacrificing quality or safety.

Technical Summary

1. Problem Statement

Anti-vascular endothelial growth factor (anti-VEGF) therapies are the standard of care for vision-threatening retinal diseases, including neovascular age-related macular degeneration (nAMD), diabetic retinopathy (DR), diabetic macular edema (DME), and retinal vein occlusion (RVO). Aflibercept (marketed as EYLEA®) is a well-established reference biologic. Aflibercept-ayyh (PAVBLU®) is a biosimilar approved by the FDA based on analytical, functional, and clinical data demonstrating no clinically meaningful differences from the reference product.

However, real-world evidence (RWE) regarding the utilization patterns, visual acuity outcomes, and safety profile of aflibercept-ayyh in routine clinical practice across diverse US patient populations was limited at the time of this study. This study aimed to fill that gap by analyzing the initial real-world experience with the biosimilar.

2. Methodology

• Study Design: A descriptive, retrospective, observational analysis.
• Data Source: Electronic Medical Records (EMRs) from the Retina Consultants of America (RCA) network, comprising 175 retina specialists across 146 locations in 24 US states.
• Study Period: December 1, 2024, to October 31, 2025.
• Study Population:
  • Sample: The first 1,000 consecutively treated eyes from 989 patients.
  • Inclusion Criteria: Adult patients (≥18 years) with a documented diagnosis of nAMD, DR, DME, or RVO; received at least one intravitreal injection of aflibercept-ayyh; and had a best recorded visual acuity (BRVA) of 20/400 or better.
  • Cohorts: Eyes were categorized as Anti-VEGF treatment-naïve (9%) or Switchers (91%, previously treated with another anti-VEGF agent).
• Outcomes Measured:
  • Utilization: Treatment patterns, injection intervals, and prior therapy history.
  • Efficacy: Change in Best Recorded Visual Acuity (BRVA) expressed in logMAR units from baseline to follow-up (≥84 days).
  • Safety: Incidence of Adverse Events of Special Interest (AESIs) within 21 days of injection, including endophthalmitis, retinal vasculitis, iritis, vitreous cells, retinal detachment, and vitreous hemorrhage.
• Statistical Analysis: Descriptive statistics were used for demographics and treatment patterns. Within-eye changes in BRVA were analyzed using the Wilcoxon signed rank test. Safety events were summarized descriptively.
• Ethics: The study was exempt from IRB oversight by Advarra due to the use of de-identified data.

3. Key Contributions

• First Large-Scale Real-World Data: Provides the first comprehensive real-world dataset on aflibercept-ayyh utilization in the US, covering a broad geographic and demographic spectrum.
• Differentiated Outcomes: Clearly distinguishes between outcomes for treatment-naïve patients (who typically show improvement) and switchers (who typically require maintenance of existing vision), validating the biosimilar's performance in both scenarios.
• Safety Validation: Confirms the safety profile of the biosimilar in a routine practice setting, specifically validating the low incidence of intraocular inflammation and other AESIs compared to historical data of the reference product.
• Biosimilar Equivalence in Practice: Adds to the body of evidence supporting the "no clinically meaningful difference" regulatory conclusion by demonstrating that real-world performance aligns with pre-approval clinical trial expectations.

4. Results

• Demographics & Baseline:
  • Median age: 79 years; 55% female; 63% never smokers.
  • Disease Distribution: nAMD (58%), RVO (19%), DME (16%), DR (7%).
  • Prior Treatment: 91% were switchers (median 21 prior injections); 9% were naïve.
• Treatment Patterns:
  • Total injections: 3,730.
  • Median injections per eye: 4 (IQR 3–5).
  • Median injection interval: 54 days overall.
  • Interval Disparity: Switchers had a median interval of 56 days, while naïve eyes had a shorter interval of 37 days (consistent with loading dose protocols).
• Visual Acuity (BRVA) Outcomes (≥84 days follow-up, n=889):
  • Switchers: Mean logMAR remained stable (0.4 to 0.4; P=0.96).
  • Naïve Eyes: Mean logMAR significantly improved (0.5 to 0.4; P<0.01).
  • Results were consistent across all diagnosis subgroups.
• Safety:
  • Iritis: 2 confirmed cases (0.05% of injections; 0.54 events per 1,000 injections). One case occurred in an eye that had previously experienced iritis with a different anti-VEGF agent. Both resolved with topical steroids.
  • Other AESIs: Zero events of endophthalmitis, retinal detachment, retinal vasculitis, vitreous hemorrhage, or vitreous cells.

5. Significance

• Clinical Confidence: The study confirms that aflibercept-ayyh performs as expected in routine clinical practice, maintaining vision in chronic/switched patients and improving vision in treatment-naïve patients.
• Safety Profile: The absence of new or unexpected safety signals, particularly regarding serious ocular adverse events, reinforces the biosimilar's safety profile as comparable to the reference product (EYLEA®).
• Healthcare System Impact: By validating the efficacy and safety of the biosimilar in real-world settings, the study supports the adoption of aflibercept-ayyh as a viable treatment option, potentially increasing access and reducing costs for patients and healthcare systems without compromising clinical outcomes.
• Limitations & Future Directions: The authors note limitations such as the short follow-up duration, lack of a concurrent control group, and reliance on EMR data. However, the findings provide a robust foundation for continued long-term monitoring and further real-world studies.

Conclusion: This analysis demonstrates that aflibercept-ayyh (PAVBLU®) is a safe and effective treatment for retinal disorders in the US, with real-world utilization patterns and outcomes consistent with the established profile of reference aflibercept.