As a vitreoretinal surgeon and managing partner of an independent physician owned retina practice, I want to raise several concerns about this study that I believe are material to its interpretation and that the retina community deserves to consider carefully.

1. Conflict of Interest and Data Provenance The data for this study was drawn exclusively from the RCA EMR database. RCA is an MSO in which Cencora holds approximately 85% ownership as of January 2025. Cencora also owns Besse Medical, one of the primary US distributors of Pavblu. The study was funded by Amgen. The presenting author is a disclosed paid Amgen consultant.

Every party involved in the design, data provision, funding, and presentation of this study has a direct financial interest in Pavblu adoption. The structural nature of these relationships, where the data source, the distributor, and the funder are financially interconnected through Cencora and Amgen, goes beyond a standard COI disclosure. These relationships raise questions about the independence of the study that should be explicitly acknowledged and discussed in the manuscript.

1. Reason for Switching: A Critical Missing Variable 91% of the study population switched from prior anti-VEGF therapy to aflibercept-ayyh. The manuscript acknowledges that reasons for switching were not captured. This is the most important missing variable in the study. In independent physician owned practices, switching decisions typically reflect individual clinical judgment based on disease activity, treatment response, and patient need. In a large MSO operating under centralized drug purchasing arrangements, switching decisions may additionally reflect institutional formulary policies or organizational priorities. The relative contribution of clinical versus institutional factors to the switching decisions observed in this study is unknown and unknowable from the data presented. A study designed to describe real world clinical adoption of a new biosimilar should be able to characterize the basis on which prescribing decisions were made. The inability to do so is a fundamental limitation that should be prominently disclosed rather than noted as a minor caveat.

2. ASP Trajectory, and Missing Economic Analysis In a buy and bill specialty, economics may drive prescribing decisions especially in larger practices. This study contains no economic analysis. Independent review of publicly available CMS Medicare Part B ASP data shows that aflibercept-ayyh entered the CMS payment system on April 1, 2025 at an ASP identical to reference aflibercept at $795.861 per mg. In its first full quarter the ASP rose to $869.084 per mg while reference aflibercept declined to $790.037 per mg. As of Q2 2026 aflibercept-ayyh is priced at $821.396 per mg versus $731.885 per mg for reference aflibercept. Aflibercept-ayyh has never been priced below the reference product since entering the CMS payment system. The retina biosimilar market has demonstrated a consistent and observable pattern in which products maintain ASPs above their reference products during periods of concentrated corporate network adoption supported by rebate arrangements. During these managed periods the reported ASP does not reflect the true net price being experienced by large corporate customers. Under Section 1847A of the Social Security Act, rebates must be reported in the quarter they are earned, not the quarter in which they are paid. When deferral arrangements expire and rebates are reported, ASPs have corrected suddenly and dramatically in this market. Independent practices making formulary decisions during the managed ASP period are doing so on the basis of pricing data that may not reflect the true market price. A real world study that omits this economic context does not provide the complete picture that independent practices need to make informed decisions.

3. Formulation Disparity and Patient Safety Equity Aflibercept-ayyh received FDA approval on August 23, 2024 in two formulations simultaneously. FDA review documents confirm that Amgen submitted separate labeling designating the single dose vial specifically as the physician sample formulation and the prefilled syringe as the commercial trade product. This was a deliberate product design decision made from the date of approval.

These two formulations carry meaningfully different preparation pathways and documented safety profiles. Published systematic review data reports consistently lower endophthalmitis rates with prefilled syringes compared to vials for intravitreal aflibercept, 0.01 to 0.02% versus 0.02 to 0.06%, attributed to reduced handling steps and contamination risk during preparation. This formulation disparity is compounded by Amgen’s own patient support program. The Amgen SupportPlus Co-Pay Program is explicitly limited to patients with commercial insurance and is expressly unavailable to patients whose costs are covered by Medicare, Medicaid, or any other federal or state healthcare program. The retina patient population is predominantly elderly and Medicare dependent. Those patients cannot access Amgen’s co-pay support and are most likely to depend on manufacturer provided samples. Amgen directs Medicare and Medicaid patients to independent third party nonprofit assistance programs over which it states it has no control and for which it takes no responsibility.

The result is a documented and foreseeable chain. Medicare and Medicaid patients are excluded from Amgen’s co-pay program (however, this is not unique to Amgen - all co-pay assistance programs generally assist commercial patients), are most dependent on manufacturer samples, and manufacturer samples are designated as single dose vials carrying a higher preparation burden and documented higher infection risk than the prefilled syringe received by commercially insured patients. The manuscript does not track formulation type as a variable, does not analyze it as a potential safety confounder, and does not address this disparity or its implications for the most financially vulnerable patients in the retina population.

1. A Note on the Broader Pattern The retina community should consider this study in the context of the commercial pattern it represents. Biosimilar manufacturers have repeatedly commissioned real world studies using data from corporate practice networks with which they have direct financial relationships, during periods of managed ASP supported by rebate deferral arrangements, to validate adoption that may be driven by institutional formulary decisions rather than independent clinical judgment. When those commercial arrangements unwind, as they consistently have in the retina biosimilar market, ASPs correct, networks transition to the next available product, and the cycle begins again.

This pattern normalizes commercially driven adoption as clinical evidence and leaves independent physician owned practices without the transparent and unbiased evidence they need to make informed formulary decisions. The patients most affected are disproportionately elderly, Medicare dependent, and reliant on manufacturer samples. They bear the downstream consequences of formulary decisions made on the basis of commercially managed evidence. The solution is not to suppress sponsored research. It is to hold it to standards that make it credible. Independent data sources. Genuine conflict of interest management. Economic outcomes alongside clinical outcomes. Transparent disclosure of rebate structures and their impact on reported ASP. Explicit discussion of patient safety equity implications when product design creates differential risk across patient populations. Until those standards are consistently applied the retina community should interpret sponsored biosimilar real world studies with appropriate skepticism regardless of which product they validate or which network’s data they use.

A Call for Independent Study The retina community would benefit from an independent study, not funded by the manufacturer, not using data from a distributor affiliated network, and not presented by paid consultants, that examines clinical and economic outcomes across a representative sample of US retina practices including independent physician owned practices.