On August 24, 2023, the FDA approved natalizumab-sztn (Tyruko; Sandoz) injection, the first biosimilar to natalizumab (Tysabri; Biogen), for the treatment of adults with relapsing forms of multiple sclerosis (MS). Natalizumab-sztn is also approved for the same indications as its reference drug Tysabri, including for inducing and maintaining clinical response and remission in adults with moderately to severely active Crohn disease with evidence of inflammation who have had an inadequate response to, or do not tolerate, conventional therapies for Crohn disease and tumor necrosis factor-alpha inhibitors.
Natalizumab-sztn has the same intravenous dosage form, route of administration, dosing regimen, and presentation as its reference drug.
The FDA approved natalizumab-sztn based on analytical, functional, and clinical data from phase 1 and phase 3 clinical trials, which met their primary end points and showed that natalizumab-sztn has the same safety, efficacy, and immunogenicity profiles as the reference drug natalizumab; this evidence demonstrated that there were no clinically meaningful differences between the 2 drugs in safety and efficacy.
“Biosimilar medications offer additional effective treatment options that have the potential to increase access for people living with relapsing forms of multiple sclerosis,” said Paul R. Lee, MD, PhD, Director of the Division of Neurology 2 in the FDA’s Center for Drug Evaluation and Research. “Today’s approval could have a meaningful impact for patients managing their disease,” Dr Lee noted.
A biosimilar is a biologic drug that is highly similar to, and has no clinically meaningful differences from, a reference biologic drug that was previously approved by the FDA for the same indications. This means that patients can expect the same safety and efficacy from the biosimilar as from the reference drug, but the biosimilar is available at a reduced cost.
“Access to affordable, high-quality healthcare is essential for people with multiple sclerosis to live their best lives. The approval of Tyruko, the first FDA-approved biosimilar disease-modifying treatment for people with relapsing forms of MS, is a milestone. Biosimilars are an important treatment option because they have no clinically meaningful differences from their reference medicines. Prescribing them can increase accessibility to affordable medications, improve adherence and help contain healthcare costs,” said Bari Talente, National MS Society’s Executive Vice President for Advocacy and Healthcare Access.
Natalizumab-sztn is approved for the treatment of relapsing forms of MS, including a clinically isolated syndrome of MS symptoms; relapsing-remitting MS, which occurs when patients have episodes of new neurologic symptoms followed by periods of stability; and active secondary progressive disease, which occurs after a relapsing-remitting MS treatment course when the patient has gradual disability that is worsening with continued relapses.
MS is among the most common causes of acquired neurologic disability in young adults and occurs more frequently in women than men. For most people with MS, episodes of relapse are initially followed by a period of remission. Over time, recovery may be incomplete, leading to a progressive decline in function and increased disability.
“Today’s approval of the first biosimilar product indicated to treat relapsing forms of multiple sclerosis furthers the FDA’s longstanding commitment to support a competitive marketplace for biological products and ultimately empowers patients by helping to increase access to safe, effective and high-quality medications at potentially lower cost,” said Sarah Yim, MD, Director of the Office of Therapeutic Biologics and Biosimilars in the FDA’s Center for Drug Evaluation and Research.
The most common side effects associated with natalizumab drugs, including natalizumab-sztn, are headache and fatigue. Other common side effects are arthralgia, urinary tract infection, lower respiratory tract infection, gastroenteritis, vaginitis, depression, pain in extremity, abdominal discomfort, diarrhea, and rash.
The prescribing information for natalizumab drugs, including natalizumab-sztn, includes a boxed warning about the increased risk for progressive multifocal leukoencephalopathy (PML), a viral brain infection that can lead to death or severe disability. The risk factors for PML include the presence of anti-JC virus antibodies, longer duration of therapy, and the use of immunosuppressants. These factors should be considered in the context of expected benefit when initiating and continuing treatment with natalizumab-sztn. Providers should monitor patients and withhold treatment with natalizumab-sztn at the first sign or symptom of PML.
Because of the risks for PML, natalizumab drugs, including natalizumab-sztn, are available only through a Risk Evaluation and Mitigation Strategy program to ensure that prescribers evaluate patients at 3 months and 6 months after the first infusion, every 6 months thereafter, and immediately and 6 months after discontinuing treatment.
Additional warnings in the prescribing information for natalizumab-sztn include the risks for herpes infections, thrombocytopenia, immunosuppression, and serious hypersensitivity reactions (eg, anaphylaxis and hepatotoxicity).