Derek Burns, PharmD, MBA, BCPS, BCSCP

This article was originally published on 

After a slow start, the growth of biosimilars in the US marketplace is accelerating and rapid expansion is expected in the next decade as many blockbuster biologics will lose exclusivity.

 Given the substantial benefits biosimilars deliver, they are coming to the forefront in many therapeutic areas. There are currently 63 biosimilars approved by the FDA, with many more pending approval.

 Studies within rheumatology, gastroenterology, dermatology, oncology, and supportive care demonstrate biosimilars deliver significant cost savings, while the FDA has determined they are safe and effective and provide the same treatment benefits and risks as the reference product.

Given the impact biosimilars have already had in various specialties, the potential for these drugs within neurology and retina practices is promising. There are already several biosimilars approved within these specialty areas, with more on the horizon. Taking a closer look at biosimilars and some best practices for efficient adoption is worthwhile, as integrating these new therapies requires careful consideration around various operational and clinical components to ensure success.

There are already several biosimilars approved within these specialty areas, with more on the horizon. | Image credit: lexiconimages - stock.adobe.com

Medical professionals in various specialties are still learning about biosimilars, so a quick overview might prove useful. A biosimilar is a biological product highly similar to an existing FDA-approved reference product and has no clinically meaningful differences. To provide detailed guidance, in 2009 the FDA established safety and bioequivalence standards, stipulating there must be evidence there are “no clinically meaningful differences in safety, purity, and potency between the biosimilar and reference product.”

 Additionally, biosimilars must be administered the same way with the same strength and dosage form, and have the same potential adverse effects as their reference product.

Biosimilars undergo rigorous FDA evaluation and safety monitoring to ensure their effectiveness, quality, and safety. The FDA approves biosimilars through a slightly different process than new drug products, known as an abbreviated pathway. This process demonstrates biosimilarity between the proposed biosimilar and its reference product, rather than independently establishing the safety and effectiveness of the biosimilar. This generally means biosimilar manufacturers are not required to conduct as many expensive clinical trials as the reference product.

The FDA also regulates biosimilar manufacturing, requiring the same quality standards that apply to the reference product. The bottom line is that biosimilars provide a safe and effective alternative, while also having the same treatment benefits and risks as the reference product.

Many different factors drive or hinder biosimilar acceptance. Provider and patient confidence, for instance, can often be a hurdle to overcome. Because biosimilars are new in both neurology and ophthalmology, apprehension is common, so education is critical in helping them overcome their concerns. Obviously, a clinical comfort level must be achieved before physicians choose to treat a patient with a biosimilar, but they also need to know there is support from the manufacturer regarding patient assistance services, consistent supply, payer coverage, and representatives available to address questions and concerns.

Patient preferences also come into play, especially when patients are transitioned to biosimilars mid-treatment. When this happens, the nocebo effect may result, where a negative outcome occurs partly from a patient’s expectation that the biosimilar is not as good as the reference product or may actually harm instead of heal.

 To avoid nocebo effects, many providers leverage biosimilars with only new starts rather than switching patients mid-treatment.

Additionally, commercial payers have tremendous power when it comes to driving adoption, as they can mandate whether a biosimilar must be used, or if the reference product is the preferred reimbursable option. A good example of this is adalimumab (Humira; AbbVie), as the adoption of its biosimilar has been inhibited by payers preferring the reference product. In the retina market, Byooviz (Biogen) and Cimerli (Sandoz), biosimilars to ranibizumab (Lucentis; Genentech), both commercially launched in Q3 and Q4 of 2022, respectively. Although it has been 2 years, McKesson is just now seeing 61% adoption of biosimilars in this specialty.

Biosimilars in the Neurology and Retina Space

In the retina market, 2 FDA-approved biosimilars are available for Lucentis: Byooviz (ranibizumab-nuna) and Cimerli (ranbizumab-eqrn). Cimerli meets additional requirements to be designated as interchangeable with Lucentis, so it can be substituted for the reference product without prescriber involvement. Interchangeability does not mean superiority; it simply indicates the product went through additional studies to receive the interchangeable label. Cimerli has the same indications as Lucentis, whereas Byooviz has all the same indications except for diabetic macular edema and diabetic retinopathy.

As of this writing, 5 biosimilars for aflibercept (Eylea; Regeneron) have been approved but only 1 has launched: afibercept-ayyh (Pavblu; Amgen). The following biosimilars have not launched: afibercept-yszy (Opuviz; Biogen), afibercept-jbvf (Yesafili; Biocon Biologics), afibercept-mrbb (Ahzantive; Formycon), and afibercept-abzv (Enzeevu; Sandoz). Yesafili, Opuviz, and Enzeevu have been approved as interchangeable, but patent litigation has caused delays in launch timing.

In June 2024, the FDA released draft guidance regarding industry considerations for demonstrating interchangeability.

 If finalized, this updated guidance would loosen requirements for biosimilar manufacturers who desire to pursue interchangeability status. Loosening these requirements and simplifying the process would reduce hurdles and barriers faced by biosimilar manufacturers.

The situation for biosimilars in neurology is a bit cloudy at present. Natalizumab-sztn (Tyruko; Sandoz), a biosimilar to natalizumab (Tysabri; Biogen) used for multiple sclerosis and Crohn disease, was approved in August 2023 with the condition that John Cunningham virus testing be approved first, and that has not happened yet. This has led to a delayed launch for Tyruko. Another medication for multiple sclerosis, ocrelizumab Ocrevus; Genentech) has patent exclusivity until 2028, so it is unlikely a biosimilar will emerge before then.

Successfully integrating biosimilars into practices requires careful planning and execution, as they impact virtually all aspects of a practice. Unfortunately, no manual exists on how to do this successfully, but looking at specialty areas that have already utilized biosimilars may be helpful. We utilized our experience in oncology to develop the following list of best practices for operationalizing biosimilars:

Decide if you will only do new starts or if you will switch patients to a biosimilar mid-treatment.

Prepare a communication plan for your staff. Make certain they understand what a biosimilar is and the benefits they provide, as well as how to confidently talk to patients about biosimilars.

Define the type of education needed for patients to adequately explain biosimilars so they understand what they are receiving. The FDA has helpful resources practices can use describing how biosimilars work and the advantages they provide.

Ensure procedures are in place to complete pre-certification 2 to 3 days before the patient’s treatment is scheduled. This gives staff time to get the right drug ordered or change the order if needed.

Review your verification process with your staff to make sure they are double checking the order against the drug vial or syringe and the drug label. This step is extremely important to prevent potential dispensing errors.

Make certain the brand name is listed in the electronic medical record. If it just says ranibizumab, as opposed to Byooviz, Cimerli, or Lucentis, it is difficult to know which product was ordered.

Determine how to build your treatment plans once biosimilars are integrated into the practice. Will there be a separate plan for Byooviz, a plan for Cimerli, and a plan for Lucentis, or will one comprehensive plan contain all 3 choices so the physician can pick the recommended treatment from the list?

Ensure all indications match the reference product. Because there are no clinically meaningful differences between biosimilars and their reference biologic, in theory it does not matter; however, payer policies could affect reimbursement if labeled indications are different.

Determine whether the biosimilar is administered the same way as the reference product. For instance, Byooviz and Cimerli are both supplied in single dose vials whereas Lucentis comes in a pre-filled syringe.

Verify how the product should be stored. Is it stored the same way as the reference product as far as room temperature versus refrigeration? As a precaution, store it on a different shelf so the wrong product is not administered.

Check to see if the formulation is the same as the reference product. Is it a powder versus a solution, and is it prepared the same way?

Confirm if the biosimilar has been assigned a J or Q code. Biosimilars do not share the same billing code as the reference product. Products may launch without an assigned code; if so, practices must bill using a miscellaneous J code, which can delay payment.

Make sure payer contract fee schedules include the biosimilars you are adding. If not, meet with payers promptly to discuss these new products.

Check if the patient has secured co-pay assistance. If so, make sure the biosimilar manufacturer can enroll the patient in the same or similar program. Otherwise, it may be better for the patient to use the reference product.

Confirm the biosimilar has been added to the practice management system so it can properly be billed.

The best practices presented here do not address all the issues a practice will face when operationalizing biosimilars, but they can provide the foundation for a comprehensive and successful plan. Operational and clinical efficiency, as well as patient and provider confidence, can be accomplished by planning and employing strategies that integrate and align biosimilars with every step of the patient journey—from diagnosis, treatment planning, patient education, pre-authorization, financial counseling and scheduling, to preparation, treatment administration, billing and follow-up care. A seamless patient experience can be created with careful planning and execution of each phase, helping ensure the patient is satisfied, that optimal outcomes are supported, and that reimbursement is secured without delay.

Practices and their staff must be nimble and willing to change their processes to successfully integrate biosimilars into the practice, and the importance of staff education in the adoption plan cannot be overstated. All staff—including the care team, revenue cycle employees, nurses, pharmacists, and technicians—must understand their part in delivering and ensuring quality care when biosimilars are used. Only then will practices and their patients be able to fully benefit from the many advantages biosimilars provide.

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Successfully integrating biosimilars into practices requires careful planning and execution, as they impact virtually all aspects of a practice.

Derek Burns, PharmD, MBA, BCPS, BCSCP

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