5 Key Facts Neurologists Should Know About the First FDA-Approved MS Biosimilar

This article was sponsored by Sandoz

Multiple Sclerosis (MS) is among the costliest chronic conditions in the United States, following only heart failure, in total economic burden.¹ Lifetime direct healthcare costs related to MS are approximately $4.8 million per patient, with annual healthcare expenses that can exceed $68,000.¹ When indirect costs –such as reduced productivity, work absences and early retirement – are factored in, the lifetime burden rises above $5.6 million per patient.¹

The use of biologics and other disease-modifying therapies (DMTs) have transformed the management of MS, helping many patients achieve improved outcomes and quality of life.² However, these treatments come at a significant cost and are a major source of high healthcare spending in MS, limiting access for some patients to these highly effective therapies.²

Biosimilars, which have no clinically significant differences from an existing US FDA-approved biologic (reference biologic), have the potential to provide more affordable, accessible options for effective treatment in MS.^3,4 By introducing competition and offering lower-priced alternatives, biosimilars can deliver meaningful savings for the healthcare system – often including providers themselves – while maintaining the efficacy and safety neurologists expect and demand.⁵ These savings can help fund continued innovation and encourage manufacturers to focus on developing new therapies that advance patient care.

The first and only FDA-approved biosimilar to treat relapsing forms of MS, TYRUKO^® (natalizumab-sztn), 300 mg/15 mL IV, was approved by the FDA in August 2023 and is now commercially available for patients in the United States.^6,7 Like its reference medicine, TYRUKO^® contains a Boxed Warning to inform healthcare professionals and patients about the increased risk of progressive multifocal leukoencephalopathy (PML) with the use of TYRUKO^®.⁸

IMPORTANT SAFETY INFORMATION

See full Important Safety Information below, or click here, and the full Prescribing Information for TYRUKO^®, including Boxed Warning.

INDICATIONS

Multiple Sclerosis (MS)

TYRUKO (natalizumab-sztn) is indicated as monotherapy for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. Natalizumab products increase the risk of progressive multifocal leukoencephalopathy (PML). When initiating and continuing treatment with TYRUKO, physicians should consider whether the expected benefit of TYRUKO is sufficient to offset this risk.

Crohn’s Disease (CD)

TYRUKO is indicated for inducing and maintaining clinical response and remission in adult patients with moderately to severely active Crohn’s disease with evidence of inflammation who have had an inadequate response to, or are unable to tolerate, conventional CD therapies and inhibitors of TNF-α. Important Limitations: In CD, TYRUKO should not be used in combination with immunosuppressants (e.g., 6-mercaptopurine, azathioprine, cyclosporine, or methotrexate) or inhibitors of TNF-α.

Five key facts neurologists should know about biosimilars and their role in MS care

1. Biosimilars are FDA approved as having no clinically meaningful differences from their reference medicines.

Biosimilars undergo a rigorous FDA review to demonstrate they are highly similar to the reference biologic, with no clinically meaningful differences in purity, safety and efficacy.^3,4 This means patients and providers can expect the same clinical results from a biosimilar as from its reference product.

One type of biosimilar, the interchangeable biosimilar, is further studied to demonstrate its ability to be substituted for the reference product without the need for a prescription; importantly, not all biosimilars receive this designation.⁹ To assess if products are interchangeable, manufacturers conduct studies in which patients alternate between the reference product and the biosimilar and compare those patients to those who are just being treated with the reference product. For the interchangeable biosimilar to be approved, the study results must demonstrate that switching between the medications is not less effective and does not increase safety risks.⁹

It is important to note that interchangeability is a regulatory designation and not a scientific one. However, they are not safer nor more effective than biosimilars that do not have this interchangeable designation.⁹

The FDA has also expressed interest in streamlining interchangeability requirements, reinforcing that all biosimilars meet the same high standards for safety, purity and potency.¹⁰

2. Biosimilars are not the same as generic medications.

Like generics, biosimilars can provide lower-cost alternatives to brand-name medicines, but there are key differences. Generics are small-molecule drugs with identical chemical structures to their reference product. Biosimilars are large, complex molecules made in living systems, which introduce natural variability.^3,4

These minor variations also occur in reference biologics – no two batches are identical – but all must meet strict FDA requirements for quality, safety and efficacy. Biosimilar developers must demonstrate through analytical, nonclinical and clinical data that any variability does not affect performance, ensuring that each biosimilar is highly similar to and has no clinically meaningful differences from its reference biologic. ^3,4

Recent FDA guidance emphasizes reducing the need for large Phase 3 efficacy trials when advanced analytical and functional data sufficiently demonstrate biosimilarity, potentially accelerating development of future biosimilars. ¹¹

3. Biosimilars can help reduce healthcare spending.

According to the 2025 U.S. Generic & Biosimilar Medicines Savings Report from the Association for Accessible Medicines, FDA-approved biosimilars generated $20.2 billion in savings in 2024. Since the first biosimilar entered the US market in 2015, these medicines have delivered $56.2 billion in cumulative savings.⁵

Generics and biosimilars together account for 90% of all U.S. prescriptions filled, while representing only 12% of total prescription drug spending. In total, these medicines generated $467 billion in savings for the U.S. healthcare system in 2024 alone, helping reduce costs for patients, employers and taxpayers.⁵

Beyond these system-wide savings, biosimilars typically launch at 15% to 35% below the price of their reference products, creating potentially meaningful cost savings that can increase patients’ access to therapies they might have been unable to afford otherwise.¹²

The considerably lower cost of biosimilars compared with their reference medicines is in part because of the Biologics Price Competition and Innovation Act of 2010, which expedited the approval process to decrease development time and cost while maintaining safety and efficacy.^3,13,14 The biosimilar approval pathway is abbreviated compared to the approval of reference products, but it still includes extensive studies that compare structure and function of the biosimilar and reference medicine.³

4. There is an FDA-approved biosimilar for treating relapsing forms of MS.

As of November 2025, TYRUKO^® is the first and only US FDA approved natalizumab biosimilar for the treatment of relapsing forms of multiple sclerosis (MS).^6,7 TYRUKO^® is approved by the FDA as monotherapy to treat all indications covered by the reference medicine including relapsing forms of MS and Crohn’s disease in adults.⁸

TYRUKO^® is available through a Risk Evaluation and Mitigation Strategy (REMS) program designed to inform prescribers, infusion site healthcare providers and patients about the risk of progressive multifocal leukoencephalopathy (PML) associated with natalizumab, including increased risk of PML with the presence of anti-JCV antibodies, longer treatment duration and prior immunosuppressant use. The program warns against concurrent use with antineoplastic, immunosuppressant or immunomodulating agents and, in patients who are immunocompromised, promotes early diagnosis and timely discontinuation in the event of suspected PML.^5,8

For additional information on the REMS program, including how to enroll, visit the TYRUKO^® REMS program website.

Sandoz entered into a global commercialization agreement for biosimilar natalizumab in 2019. Under this agreement, Polpharma Biologics will maintain responsibility for the development of medicine, manufacturing and supply of the drug substance.^6,7 Through an exclusive global license, Sandoz has the rights to commercialize and distribute it in all markets.⁶ In addition to the US, TYRUKO^® is now available in 14 European countries.⁷

Sandoz has partnered with Labcorp, a global leader of innovative and comprehensive laboratory services, to develop and validate a laboratory-developed test (LDT) for detecting the presence of anti-JCV antibodies.⁷ Labcorp will offer the TYRUKO^® JCV Testing Program at no cost to eligible patients, with Sandoz covering the cost of the test.⁷

5. TYRUKO^® matches the reference medicine in efficacy, safety, and immunogenicity.

In the randomized, double-blind phase 3 Antelope study (NCT04115488) in adults with relapsing-remitting MS, TYRUKO^® (natalizumab-sztn) demonstrated equivalent efficacy, safety and immunogenicity to reference natalizumab.² The primary endpoint – the cumulative number of new active brain MRI lesions over 24 weeks – met prespecified similarity margins (model-based mean difference 0.17; 95% CI, - 0.61 to 0.94).²

Safety and immunogenicity findings were comparable between treatment groups. Patients who switched from reference natalizumab to TYRUKO^® experienced no increase in treatment-emergent adverse events or seroconversion compared to those who continued on reference therapy.² Together, these data support that TYRUKO^® is highly similar to, and has no clinically meaningful differences from, its reference biologic.

Therefore, the FDA concluded that TYRUKO^® adequately demonstrated biosimilarity in this setting, as no clinically significant differences in efficacy, safety, and immunogenicity between the agents were observed.²

Conclusion Disease Modifying Therapies (DMTs), particularly biologics that are used to treat MS, can be cost-prohibitive for people living with MS. Biosimilars like TYRUKO^®, the first and only FDA-approved biosimilar for the relapsing forms of MS, can offer an alternative that has the potential to reduce the cost burden for patients and the healthcare system, fuel increased innovation across areas of highest unmet need, and help people access essential medicines – now and in the future.^5,8

IMPORTANT SAFETY INFORMATION (CONTINUED)

CONTRAINDICATIONS

• Patients who have or have had PML
• Patients who have had a hypersensitivity reaction to natalizumab products or any of the ingredients in TYRUKO

WARNINGS AND PRECAUTIONS

Progressive Multifocal Leukoencephalopathy (PML)

• Infection by the JC Virus (JCV) is required for the development of PML
• Patients who are anti-JCV antibody negative are still at risk for the development of PML due to the potential for a new JCV infection or a false negative test result. Therefore, patients with a negative test result should be retested periodically
• There are no known interventions that can reliably prevent PML or that can adequately treat PML if it occurs
• Postmarketing data suggest that the risk of developing PML may be associated with relative levels of serum anti-JCV antibody compared to a calibrator as measured by ELISA (often described as an anti-JCV antibody index value)
• MRI findings may be apparent before clinical signs or symptoms suggestive of PML. Monitoring with MRI for signs that may be consistent with PML may be useful, and any suspicious findings should lead to further investigation to allow for an early diagnosis of PML, if present. Consider monitoring patients at high risk for PML more frequently. Lower PML-related mortality and morbidity have been reported following natalizumab products discontinuation in patients with PML who were initially asymptomatic compared to patients with PML who had characteristic clinical signs and symptoms at diagnosis
• PML has been reported after discontinuation of natalizumab products in patients who did not have findings suggestive of PML at the time of discontinuation. Patients should continue to be monitored for any new signs or symptoms that may be suggestive of PML for at least 6 months after discontinuation of TYRUKO
• Adverse events that may occur during plasma exchange (PLEX) include clearance of other medications and volume shifts, which have the potential to lead to hypotension or pulmonary edema. Although PLEX has not been prospectively studied in natalizumab-treated patients with PML, it has been used in such patients in the postmarketing setting to remove natalizumab more quickly from the circulation. There is no evidence that PLEX has any benefit in the treatment of opportunistic infections such as PML
• JCV infection of granule cell neurons in the cerebellum, i.e., JCV granule cell neuronopathy (GCN), with symptoms similar to PML, has been reported in patients treated with natalizumab products. JCV GCN can occur with or without concomitant PML and can cause cerebellar dysfunction. Diagnosis and management of JCV GCN should follow guidance provided for PML
• Immune reconstitution inflammatory syndrome (IRIS) has been reported in the majority of natalizumab product-treated patients who developed PML and subsequently discontinued natalizumab products. In almost all cases, IRIS occurred after PLEX was used to eliminate circulating natalizumab products. It presents as a clinical decline in the patient’s condition after natalizumab product removal (and, in some cases, after apparent clinical improvement) that may be rapid, can lead to serious neurological complications or death, and is often associated with characteristic changes in the MRI. Natalizumab products have not been associated with IRIS in patients discontinuing treatment with natalizumab products for reasons unrelated to PML. In natalizumab product-treated patients with PML, IRIS has been reported within days to several weeks after PLEX. Monitoring for development of IRIS and appropriate treatment of the associated inflammation should be undertaken

TYRUKO REMS Program

• Because of the risk of PML, TYRUKO is available only through a restricted distribution program under a REMS called the TYRUKO REMS Program
• Patients must be enrolled in the TYRUKO REMS Program, read the Medication Guide, understand the risks associated with TYRUKO, and complete and sign the Patient Enrollment Form for each patient

Herpes Infections – Encephalitis, Meningitis, and Acute Retinal Necrosis (ARN)

• Natalizumab products increase the risk of developing encephalitis and meningitis caused by herpes simplex and varicella zoster viruses
• Serious, life-threatening, and sometimes fatal cases have been reported in the postmarketing setting in multiple sclerosis patients receiving natalizumab products
• The duration of treatment with natalizumab products prior to onset ranged from a few months to several years
• Monitor patients receiving TYRUKO for signs and symptoms of meningitis and encephalitis. If herpes encephalitis or meningitis occurs, TYRUKO should be discontinued, and appropriate treatment for herpes encephalitis/meningitis should be administered
• Patients being administered natalizumab products are at a higher risk of ARN, a fulminant viral infection of the retina caused by the family of herpes viruses. Patients with eye symptoms such as decreased visual acuity, redness, or eye pain should be referred for retinal screening as serious cases of ARN can lead to blindness of 1 or both eyes
• Following clinical diagnosis of ARN, consider discontinuation of TYRUKO

Hepatotoxicity

• Clinically significant liver injury, including acute liver failure requiring transplant, has been reported in patients treated with natalizumab products in the postmarketing setting
• Signs of liver injury, including markedly elevated serum hepatic enzymes and elevated total bilirubin, occurred as early as 6 days after the first dose; signs of liver injury have also been reported for the first time after multiple doses
• TYRUKO should be discontinued in patients with jaundice or other evidence of significant liver injury (e.g., laboratory evidence)

Hypersensitivity/Antibody Formation

• Hypersensitivity reactions have occurred in patients receiving natalizumab products, including serious systemic reactions (e.g., anaphylaxis) which occurred at an incidence of <1%
• Reactions usually occur within 2 hours of the start of the infusion. Symptoms associated with these reactions can include urticaria, dizziness, fever, rash, rigors, pruritus, nausea, flushing, hypotension, dyspnea, and chest pain
• If a hypersensitivity reaction occurs, discontinue administration of TYRUKO and initiate appropriate therapy. Patients who experience a hypersensitivity reaction should not be re-treated with TYRUKO
• Hypersensitivity reactions were more frequent in patients with antibodies to natalizumab compared with patients who did not develop antibodies to natalizumab in both MS and Crohn’s disease (CD) studies
• Patients who receive natalizumab products for a short exposure (1 to 2 infusions) followed by an extended period without treatment are at higher risk of developing anti-drug antibodies and/or hypersensitivity reactions on re-exposure, compared to patients who received regularly scheduled treatment

Immunosuppression/Infections

• The immune system effects of natalizumab products may increase the risk for infections
• Concurrent use of antineoplastic, immunosuppressant, or immunomodulating agents may further increase the risk of infections over the risk observed with use of natalizumab alone
• In Study MS1, certain types of infections—including pneumonias and urinary tract infections (including serious cases), gastroenteritis, vaginal infections, tooth infections, tonsillitis, and herpes infections—occurred more often in natalizumab-treated patients than in placebo-treated patients. One opportunistic infection, a cryptosporidial gastroenteritis with a prolonged course, was observed in a patient who received natalizumab in Study MS1
• In Studies MS1 and MS2, an increase in infections was seen in patients concurrently receiving short courses of corticosteroids. However, the increase in infections in natalizumab-treated patients who received steroids was similar to the increase in placebo-treated patients who received steroids
• In a long-term safety study of patients with multiple sclerosis, opportunistic infections (pulmonary mycobacterium avium intracellulare, aspergilloma, cryptococcal fungemia and meningitis, and Candida pneumonia) have been observed in <1% of natalizumab-treated patients
• In CD clinical studies, opportunistic infections (pneumocystis carinii pneumonia, pulmonary mycobacterium avium intracellulare, bronchopulmonary aspergillosis, and burkholderia cepacia) have been observed in <1% of natalizumab-treated patients; some of these patients were receiving concurrent immunosuppressants
• In Studies CD1 and CD2, an increase in infections was seen in patients concurrently receiving corticosteroids. However, the increase in infections was similar in placebo-treated and natalizumab-treated patients who received steroids. Concurrent use of antineoplastic, immunosuppressant, or immunomodulating agents may further increase the risk of infections, including PML and other opportunistic infections, over the risk observed with use of natalizumab. The safety and efficacy of natalizumab in combination with antineoplastic, immunosuppressant, or immunomodulating agents have not been established. Patients receiving chronic immunosuppressant or immunomodulatory therapy or who have systemic medical conditions resulting in significantly compromised immune system function should not ordinarily be treated with natalizumab. The risk of PML is also increased in patients who have been treated with an immunosuppressant prior to receiving natalizumab
• For patients with Crohn's disease who start TYRUKO while on chronic corticosteroids, commence steroid withdrawal as soon as a therapeutic benefit has occurred. If the patient cannot discontinue systemic corticosteroids within six months, discontinue TYRUKO

Laboratory Test Abnormalities

• In clinical trials, natalizumab was observed to induce increases in circulating lymphocytes, monocytes, eosinophils, basophils, and nucleated red blood cells. Observed changes persisted during natalizumab exposure, but were reversible, returning to baseline levels usually within 16 weeks after the last dose. Elevations of neutrophils were not observed. Natalizumab induces mild decreases in hemoglobin levels (mean decrease of 0.6 g/dL) that are frequently transient

Hematological Abnormalities

• Cases of thrombocytopenia, including immune thrombocytopenic purpura (ITP), have been reported with the use of natalizumab products in the postmarketing setting. Symptoms of thrombocytopenia may include easy bruising, abnormal bleeding, and petechiae. Delay in the diagnosis and treatment of thrombocytopenia may lead to serious and life-threatening sequelae. If thrombocytopenia is suspected, TYRUKO should be discontinued
• Cases of neonatal thrombocytopenia and anemia have been reported in newborns with in utero exposure to natalizumab products. A complete blood count (CBC) should be obtained in neonates with in utero exposure to TYRUKO

Adverse Reactions

The most common adverse reactions (incidence ≥10%) were headache and fatigue in both the multiple sclerosis (MS) and Crohn’s disease (CD) studies. Other common adverse reactions (incidence ≥10%) in the MS population were arthralgia, urinary tract infection, lower respiratory tract infection, gastroenteritis, vaginitis, depression, pain in extremity, abdominal discomfort, diarrhea NOS, and rash. Other common adverse reactions (incidence ≥10%) in the CD population were upper respiratory tract infections and nausea.

The most common adverse reactions in Study MS1 reported at an incidence of ≥10% with natalizumab and ≥2% difference with placebo were headache (38% vs 33%), fatigue (27% vs 21%), infusion reactions (24% vs 18%), urinary tract infections (21% vs 17%), arthralgia (19% vs 14%), depression (19% vs 16%), pain in extremity (16% vs 14%), rash (12% vs 9%), gastroenteritis (11% vs 9%), and vaginitis (10% vs 6%)

The most frequently reported serious adverse reactions in Study MS1 were infections (3.2% vs 2.6% in placebo, including urinary tract infection [0.8% vs 0.3%] and pneumonia [0.6% vs 0%]), acute hypersensitivity reactions (1.1% vs 0.3%, including anaphylaxis/anaphylactoid reaction [0.8% vs 0%]), depression (1.0% vs 1.0%, including suicidal ideation or attempt [0.6% vs 0.3%]), and cholelithiasis (1.0% vs 0.3%). In Study MS2, serious adverse reactions of appendicitis were also more common in patients who received natalizumab (0.8% vs 0.2% in placebo).

The most common adverse reactions in induction Studies CD1 and CD2 reported at an incidence of ≥10% with natalizumab and ≥2% difference with placebo were headache (32% vs 23%), fatigue (10% vs 8%), upper respiratory tract infection (22% vs 16%), and nausea (17% vs 15%). The most common adverse reactions in maintenance Study CD3 reported at an incidence of ≥10% with natalizumab and ≥2% difference with placebo were headache (37% vs 31%), influenza-like illness (11% vs 6%), influenza (12% vs 5%), and back pain (12% vs 8%). In the controlled CD clinical trials, infusion-related reactions occurred in approximately 11% of patients treated with natalizumab compared to 7% of placebo-treated patients.

The following serious adverse reactions in the induction Studies CD1 and CD2 were reported more commonly with natalizumab than placebo and occurred at an incidence of at least 0.3%: intestinal obstruction or stenosis (2% vs 1% in placebo), acute hypersensitivity reactions (0.5% vs 0%), abdominal adhesions (0.3% vs 0%), and cholelithiasis (0.3% vs 0%). Similar serious adverse reactions were seen in the maintenance Study CD3.

USE IN SPECIFIC POPULATIONS

Based on animal data, natalizumab may cause fetal harm. TYRUKO^® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Please click to see full Prescribing Information for TYRUKO^®.

References

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3. Biosimilar regulatory review and approval. FDA. Last accessed November 20, 2025. https://www.fda.gov/media/151061/download
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6. Sandoz receives FDA approval for Tyruko (natalizumab-sztn), first and only FDA-approved biosimilar for relapsing forms of multiple sclerosis. Sandoz. August 25, 2023. Last accessed November 20, 2025. https://www.us.sandoz.com/news/fda-approves-tyruko-natalizumab-sztn-first-and-only-fda-approved-biosimilar-relapsing-forms
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