Biosimilars Enter the Multiple Sclerosis Treatment Paradigm

Participating in the panel are, from left, Patricia Melville, MSN, RN, NP-C; John Kramer, PA-C; Amy Perrin Ross, MSN, APN, CNRN, MSCN; and Aliza Ben-Zacharia, PhD, DNP, RN, ANP-BC, FAAN.

MULTIPLE SCLEROSIS (MS) is a disorder of the central nervous system characterized by inflammation, demyelination, and degenerative changes that can lead to functional loss and disability. Over the past 2 decades, the FDA has approved several disease-modifying therapies for relapsing forms of the disease, which include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease. In 2017, ocrelizumab (Ocrevus; Genentech) became the first approved therapy for primary progressive MS.

With the advances in MS therapies, several industry leaders have taken interest in developing biosimilars to previously approved medications. These biosimilars are generally made from living sources, are nearly identical to the original biologics, endure a faster development process, and are typically less expensive than the original biologic. Those who treat patients with MS believe several new biosimilars are expected to enter the market in the coming years. With this in mind, NeurologyLive^® assembled a panel of advanced practice providers from institutions across the United States to offer insight on the who, what, and where of biosimilars; their potential role in MS; and the clinical data on biosimilars currently in development. The panel included Amy Perrin Ross, MSN, APN, CNRN, MSCN; Patricia Melville, MSN, RN, NP-C; Aliza Ben-Zacharia, PhD, DNP, RN, ANP-BC, FAAN; and John Kramer, PA-C.

Mechanisms and Immunogenicity of Biosimilars

Ben-Zacharia, an assistant professor at the Hunter-Bellevue School of Nursing at Hunter College, part of the City University of New York, in New York, began the discussion on the differences between biosimilars and reference products. She noted that biosimilars must have a similar active ingredient but that they may have different inactive ingredients, different packaging, and a different appearance.

Biosimilars may also have an easier regulatory path, she mentioned. Although it’s the same “rigorous” process, the path for biosimilars is more streamlined because these therapies must show clinical equivalence to already approved biologics, whereas biologics must prove efficacy and safety compared with a placebo-controlled drug.

Biosimilars are expected to have a major impact on the global burden of costs for MS care. “I don’t know whether to say unfortunately or fortunately there is a decrease, and we often save millions of dollars with the biosimilars,” Ben-Zacharia said. “However, they are less expensive by about 10% to 20% in the United States; in Europe, it’s about 20% to 35%. Yes, cost goes down. I was so impressed to see, for example, John [Kramer], you mentioned rituximab. There was a decrease in 2019 and 2020, with a savings of $3 million from using biosimilars, which is impressive.”

Perrin Ross, a board-certified neuroscience nurse and the Neuroscience Program coordinator at Loyola University Medical Center in Maywood, Illinois, went on to say that it’s “incumbent upon us all in the health care arena to do what we can to rein in costs. If that means using biosimilars, then that’s fine.”

The longer that patients are on a biologic or biosimilar, the higher the risk for developing antibodies to that drug. These antibodies may eliminate or reduce the efficacy of the medication and sometimes lead to life-threatening complications, Ben-Zacharia said. Thus, following and monitoring patients and recognizing that antibodies may be transient are important to the care of patients with MS.

“I think it’s critically important, particularly when you think about our anti-CD20 [monoclonal antibodies],” Melville stated. Melville, a clinical instructor in neurology at Stony Brook Medicine in New York, added, “Some of them are chimeric models, some of them are humanized. [With] humanized, you’re going to have less immunogenicity. You’re going to have less in the way of allergic-type reactions and things. This is something that I consider when I’m prescribing for my patients.”

FDA’s Approval of First Natalizumab Biosimilar

Aliza Ben-Zacharia, PhD, DNP, RN, ANP-BC, FAAN, talks about the cost effect of biosimilars, as Amy Perrin Ross, APN, MSN, CNRN, MSCN, listens on

In August 2023, the FDA approved Sandoz’s and Polpharma Biologics’ injection treatment natalizumab-sztn (Tyruko) as the first biosimilar to the approved formulation of natalizumab (Tysabri; Biogen), further advancing the treatment possibilities for patients. The biosimilar’s approval was based on findings from the phase 3 Antelope study (NCT04115488), in which the agent matched reference natalizumab in terms of efficacy, safety, and immunogenicity.^1,2

In the discussion, panelists spoke about the similarities between Antelope and AFFIRM (NCT00027300), the phase 3 study that led to natalizumab’s approval in the early 2000s. Although both were similar in design, the Antelope study had a more specific MRI eligibility criterion. Additionally, Ben-Zacharia noted concerns with the length of Antelope, which was a 24-week study in comparison with the 2-year AFFIRM trial. Each study comprised hundreds of patients who came into the study with at least 1 documented relapse in the prior year.

“It’s very interesting that they were both in different eras,” Melville said. “When you think about the AFFIRM and Antelope trials, [they were] almost 15 to 20 years apart. It shows how our knowledge of MS has changed, our expectations, [and how] our outcome measures in trials have changed as well.”

“It’s very interesting that they were both in different eras. When you think about the AFFIRM and Antelope trials, [they were] almost 15 to 20 years apart. It shows how our knowledge of MS has changed, our expectations, [and how] our outcome measures in trials have changed as well.”

– Patricia Melville, MSN, RN, NP-C

Kramer, a physician assistant in the Department of Neurology at Vanderbilt University Medical Center in Nashville, Tennessee, claimed that the use of rituximab as a biosimilar has helped clinicians become accustomed to this process. “That was our first exposure to the use of a biosimilar in the world of neuro-autoimmune disease,” he stated. “My hope is that in other autoimmune conditions [and] other biologic products, there is this framework in place that ideally will allow us to feel a lot more comfortable right out of the gate with these newer biosimilars for patients with MS.”

Implementing Biosimilars in Clinical Practice

As more biosimilars are approved, the clinical community will need to find strategies to ensure that these agents are available in a timely manner. As the conversation went on, the panelists discussed the advantages of updated electronic medical records (EMRs).

“It’s important because the EMR is a tool to show us and demonstrate these medications and the options we have,” Ben-Zacharia stated. “It allows us to choose the options. However, if third-party payers have different ideas about our prescribing, sometimes we justify, we fight. But sometimes if we feel that the biosimilar had good data, then we can prescribe and improve access to care and medication. That will be an important strategy to expedite that formulary phase.”

As these biosimilars become more commonplace in clinic, the time for raising awareness from an educational standpoint is now, Kramer said. In the discussion, he talked about the importance of translating information to key members such as staff nurses and infusion nurses who may be administering these biosimilar products to patients.

“They’re going to clearly need a certain level of education so that they feel comfortable that they can answer questions so that infusion moves forward that day, and we can have the patient come in for a follow-up visit with us to help explain better,” Kramer said. “I think there’s an educational opportunity here for the entire MS care team.”

In the conclusion of the discussion, the panelists expressed their need for additional real-world data as more biosimilars become integrated into clinical care. Additionally, collaboration with other specialty professions that have experience with biosimilars, such as oncologists or rheumatoid arthritis professionals, should be explored more and may ultimately help MS neurologists navigate some of the questions that arise.

REFERENCES
1. FDA approves first biosimilar to treat multiple sclerosis. News release. FDA. August 24, 2023. Accessed October 11, 2023. https://www.fda.gov/news-events/press-announcements/ fda-approves-first-biosimilar-treat-multiple-sclerosis
2. Hemmer B, Wiendl H, Roth K, et al. Efficacy and safety of proposed biosimilar natalizumab (PB006) in patients with relapsing-remitting multiple sclerosis: the Antelope phase 3 randomized clinical trial. JAMA Neurol. 2023;80(3):298-307. doi:10.1001/jamaneurol.2022.5007