Biosimilars have been used across the global healthcare landscape for the last 15 years in a variety of therapeutic areas.1 In 2009, safety and bioequivalence standards were established in the United States for biosimilars, with the US Food and Drug Administration (FDA) requiring evidence there are “no clinically meaningful differences in safety, purity, and potency between the biosimilar and reference product.”2 Real-life studies have demonstrated biosimilars deliver significant cost savings without affecting the quality of patient care,1 and there is every reason to believe they will have a similar impact within ophthalmology and retina practices.
While there are only 2 biosimilars within the retina space available on the market today, others are currently in development.3 Given the potential advantages of biosimilars in retina practices, it is worth closely examining what they can provide, as well as the various strategies retina practices can employ to begin safely and efficiently incorporating biosimilars into their operations.
Biosimilars in the Retina Market
In the retina space today, there are currently 2 FDA approved biosimilars for Lucentis (Genentech): Byooviz (ranibizumab-nuna; Biogen) and Cimerli (ranibizumab-eqrn; Sandoz). Cimerli is considered interchangeable with Lucentis, meaning that it meets additional requirements and may be substituted for the reference product without prescriber involvement. Additionally, 5 biosimilars for Eylea (Regeneron) have recently been FDA approved but are not yet available on the market: Opuviz (aflibercept-yszy; Samsung Bioepis), Yesafili (aflibercept-jbvf; Biocon Biologics), Ahzantive (aflibercept-mrbb; Formycon AG), Enzeevu (afibercept-abzv; Sandoz), and Pavblu (aflibercept-ayyh; Amgen). Yesafili, Opuviz, and Enzeevu have been FDA approved as interchangeable; however, patent litigation may delay launch timing.
Currently, there are several other retina biosimilars in development. Biosimilars for ranibizumab awaiting FDA approval include CKD-701 (Chong Kun Dang Pharmaceutical) and Xlucane (Xbrane Biopharma), while aflibercept biosimilars in development include AVT106 (Alvotech), SOK583A1 (Sandoz), CT-P42 (Celltrion), and SCD411 (Sam Chun Dang Pharmaceutical).3
In June 2024, the FDA released draft guidance regarding industry considerations for demonstrating interchangeability.4 If finalized, this updated guidance would loosen requirements for biosimilar manufacturers who wish to pursue interchangeability status. Under the draft guidance, manufacturers would no longer be required to conduct switching studies, which involve confirming no issues when switching patients from the reference product to the biosimilar and then back. The FDA’s experience now suggests the risk of safety concerns or diminished efficacy is insignificant following switches in product. Removing these requirements and simplifying the process would reduce hurdles and barriers faced by biosimilar manufacturers.
The Many Advantages of Biosimilars
As biosimilars continue expanding within the retina market, there are numerous benefits for both healthcare professionals and patients. For instance, competition in the market leads to cost savings. Substantial evidence shows biosimilars are increasingly becoming a driver of competition and savings in the United States.5 The biosimilars market has resulted in $21 billion in cumulative savings in the United States for Medicare, employers, patients, and the healthcare system over the 6-year period from 2017 through 2022 within the rheumatology, gastroenterology, dermatology, oncology, and supportive care spaces.6
Patient access to life saving medications is also increased with biosimilars, as they provide the opportunity to utilize more affordable alternatives to reference biologic drugs.7 Additionally, biosimilars provide product differentiation with Group Purchasing Organization (GPO) contracts.
Strategies for Introducing Biosimilars into Clinical Practice
When incorporating biosimilars into a retina practice, providers must consider certain factors to ensure integration is both safe and efficient. To ensure the highest level of success for all key stakeholders, retina providers can leverage a vast amount of knowledge available in various multispecialty disease states.
The following list of considerations is a starting point, because operations within each practice environment will be different, but it does provide a good overview of what would be helpful to know when integrating biosimilars into retina practices, both large and small.
Operational Considerations
1. Will the practice use biosimilars with new starts, or will patients be switched over mid-treatment?
2. Does the staff understand what a biosimilar is and can they talk to patients about it?
3. Has the practice developed an educational plan for patients? Biosimilars can be confusing and concerning to patients.
4. Does the practice have procedures to ensure precertification is completed 2 to 3 days before the patient is scheduled to receive the drug? This gives the staff time to order the right drug or change an order if needed.
5. Does the practice have a double-check process in place? It is extremely important that the order, the drug vial or syringe, and the drug label are all compared and then double checked by a separate staff member to prevent potential dispensing errors.
6. Is the brand name of the biosimilar listed in the EMR? It can be difficult to know which product was ordered if the EMR just says ranibizumab, as opposed to the more specific drug brand name Byooviz, Cimerli, or Lucentis.
7. How will treatment plans be built once the practice is ready to integrate biosimilars into the practice? Will there be a separate plan for each reference drug and biosimilar or will 1 plan include all of them so the physician can pick which drug they will use from a list. The best practice is to have 1 plan that includes all the choices, but clinics may have their own process that works well for them.
Clinical Considerations
1. Do all indications of the biosimilar match the reference product? There are no clinical meaningful differences in the biosimilar product, so in theory it does not matter, but this can matter when it comes to reimbursement from the payer.
2. Is the biosimilar administered the same as the reference product (eg, time and route)?
3. Is the biosimilar stored the same way as the reference product as far as room temperature vs refrigeration? Consider storing biosimilars on different shelves so the wrong product is not administered in error.
4. Is the formulation of the biosimilar the same as the reference product? For example, is it a powder vs solution, and is it prepared the same way? Formulation differences can affect operational workflow.
Revenue Cycle Considerations
1. Has the Centers for Medicare and Medicaid Services (CMS) assigned an HSPCS code to the biosimilar? Biosimilars do not share the same billing code as the reference product. Some products will launch without an assigned code, and then the practice must bill using a miscellaneous J code, which can delay payment. Because biosimilars have their own J or Q code, they will have their own average sale price (ASP) and be reimbursed differently.
2. Do payer contract fee schedules include the biosimilar(s) planned for use? If not, consider working with the payers to get the biosimilar(s) added.
3. Does the patient have copay assistance secured? If so, make sure the biosimilar manufacturer can enroll the patient in a similar program. Otherwise, it may be better for the patient to use the reference product.
4. Has the biosimilar been added to the practice management system so it can be billed properly?
Potential Risks to Consider
Like other areas of healthcare, there are challenges and unanticipated roadblocks that come along with incorporating biosimilars into retina practices that providers should plan for, many of which resemble risks that accompany the introduction of any new therapy or service within a practice. As with any drug, there is the possibility of errors related to ordering, billing the wrong product can also occur, resulting in nonpayment. Finally, biosimilars can be confusing and frustrating to patients and staff when uninformed, which is why robust education and communication is vital to the success of integrating them into a retina practice.
Achieving Success Through Detailed Planning
Incorporating biosimilars into a retina practice requires thoughtful planning, diligent oversight, and an adaptable mindset. To be successful, retina practices should have a detailed implementation plan in place to ensure proper focus is placed on patient safety, operational efficiency, and financial stewardship of the practice.
Retina practices should take the time to develop a comprehensive communication plan for staff and patients to see the best results possible when incorporating biosimilars. The staff must have the necessary knowledge of what biosimilars are and know how to effectively discuss safety, efficacy and cost benefits these alternatives provide patients. While some specific handouts for patients may need to be produced, there is a wealth of educational material already available, such as resources from the FDA, that explain biosimilars and the benefits they provide to patients.
These suggestions and strategies will help retina practices get started with biosimilars, but to succeed, they must be nimble and willing to change quickly, as many new biosimilars are on the horizon that may require different strategies or adjustments within the practice. RP
References
1. Hariprasad SM, Gale RP, Weng CY, Ebbers HC, Rezk MF, Tadayoni R. An introduction to biosimilars for the treatment of retinal diseases: a narrative review. Ophthalmol Ther. 2022;11(3):959-982. doi:10.1007/s40123-022-00488-w
2. US Department of Health and Human Services, et al. Scientific considerations in demonstrating biosimilarity to a reference product. April 2015. Accessed September 27, 2024. https://www.fda.gov/media/82647/download
3. Elhusseiny A, Ghaleb R, et al. Biosimilars in Ophthalmology. American Academy of Ophthalmology Eyewiki. March 19, 2024. Accessed September 27, 2024. https://eyewiki.org/Biosimilars_in_Ophthalmology#An_Overview
4. US Food and Drug Administration. Considerations in demonstrating interchangeability with a reference product: update; draft guidance for industry. Federal Register. 89;52060. June 21, 2024. Accessed September 27, 2024. https://www.federalregister.gov/documents/2024/06/21/2024-13429/considerations-in-demonstrating-interchangeability-with-a-reference-product-update-draft-guidance
5. Seidlitz L. Biosimilars drive savings, but the IRA undermines their development. Pharmaceutical Research and Manufacturers of America. December 14, 2023. Accessed September 27, 2024. https://phrma.org/Blog/Biosimilars-drive-savings-but-the-IRA-undermines-their-development
6. Amgen Biosimilars. 2022 Biosimilar Trends Report. Accessed September 27, 2024. https://www.amgenbiosimilars.com/commitment/2022-Biosimilar-Trends-Report
7. Hobbs AL, Crawford JP. Biosimilars and implications for pharmacy practice: ready or not, here they come! Pharm Pract (Granada). 2019;17(3):1659. doi:10.18549/PharmPract.2019.3.1659
