Tyruko (natalizumab-sztn) / Polpharma, Sandoz - LARVOL DELTA

TREAT-MS: Traditional Versus Early Aggressive Therapy for Multiple Sclerosis Trial (clinicaltrials.gov) - P=N/A | N=900 | Completed | Sponsor: Johns Hopkins University | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Multiple Sclerosis

Natalizumab and Tyruko (natalizumab biosimilar) for treating highly active relapsing-remitting multiple sclerosis after at least one disease-modifying therapy: a systematic review and economic model. (PubMed, Health Technol Assess) - "Fingolimod, glatiramer acetate, interferon beta-1a, interferon beta-1b and peginterferon beta-1a were associated with an increased treatment discontinuation (29 studies, 13 interventions)...Data in highly active relapsing-remitting multiple sclerosis were available for fingolimod, ocrelizumab, alemtuzumab, cladribine, interferon beta, autologous haematopoietic stem cell treatment and placebo...60. See the NIHR Funding and Awards website for further award information."

Clinical • Journal • Review • CNS Disorders • Inflammation • Multiple Sclerosis

FDA's Approval Summary of the First Biosimilar to Natalizumab for the Treatment of Multiple Sclerosis and Crohn's Disease. (PubMed, J Clin Pharmacol) - "The PD assessment incorporated a panel of biomarkers indicative of target engagement and downstream biological responses. The current case underscores the importance of the 351(k) pathway and highlights how the PD-based approach, in conjunction with comparative analytical assessments and PK data, supported the approval of the biosimilar through a study design relying on fewer subjects and a shorter duration compared to an efficacy study."

FDA event • Journal • CNS Disorders • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease • Multiple Sclerosis

Safety and patient experiences with the natalizumab biosimilar in multiple sclerosis treatment. (PubMed, Mult Scler Relat Disord) - "While most patients perceived the biosimilar as equivalent to the originator, overall satisfaction was lower, and some reported more side effects. As these findings differ from blinded approval trials, a nocebo effect may influence patient perceptions in real-world settings when switching from originator to biosimilar natalizumab."

Journal • CNS Disorders • Multiple Sclerosis

Natalizumab for the Treatment of People With Inflammatory Demyelination Suggestive of Multiple Sclerosis, or Definite Multiple Sclerosis, at First Presentation (AttackMS) (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: Queen Mary University of London | Suspended ➔ Recruiting | Trial completion date: Jan 2028 ➔ Oct 2027 | Trial primary completion date: Jan 2028 ➔ Oct 2027

Enrollment open • Trial completion date • Trial primary completion date • CNS Disorders • Multiple Sclerosis

Sandoz launches TYRUKO (natalizumab-sztn) in US, as first and only multiple sclerosis biosimilar (Sandoz Press Release)

Biosimilar launch • Multiple Sclerosis

Natalizumab: originator product and biosimilar use in multiple sclerosis (ECTRIMS 2025) - "In a cohort of Natalizumab (Tysabri) treated patients, an unexpectedly large proportion of patients who were switched to the biosimilar Tyruko experienced a range of symptoms most prominently impacting mobility, but we found no evidence of radiological progression. Higher lymphocyte counts could result from a higher impact of Tyruko in those who switched. Conversely, the increasing symptoms were reminiscent of prior studies where less frequent Tysabri dosing was implemented."

Late-breaking abstract • CNS Disorders • Fatigue • Multiple Sclerosis

A comparison of JC virus assay performance provided with originator and biosimilar natalizumab (ECTRIMS 2025) - "These observed differences create uncertainty in how to counsel patients and best carry out PML surveillance and risk mitigation. Specific concerns include overestimating risk leading to increased patient concern, increased monitoring burden and associated healthcare costs, and lack of access to a highly effective therapy. UK consensus guidance has been developed to assist clinical management and patient counselling in the context of this switch."

Efficacy and safety of switching between originator and biosimilar natalizumab in Norway (ECTRIMS 2025) - "Preliminary results indicate that serum levels and ADAbs are similar between original and biosimilar NTZ, while subjective side effects differ. Four times as many patients were JCV-positive with the Immunowell test compared to the Stratify test. For both clinicians and pwMS, it is important to assess the effect of changing from biosimilar iv to original sc NTZ in a larger cohort."

Clinical • CNS Disorders • Fatigue • Multiple Sclerosis • Musculoskeletal Pain • Rare Diseases

John Cunningham Virus (JCV) Serostatus Discrepancy by two Different Tests: Impact on the Clinicians and Patients Choices in a Cohort Multiple Sclerosis Patients Treated with Natalizumab (ECTRIMS 2025) - "A high rate of discrepancy between the Stratify JCV and Immunowell JCV test results can be expected, particularly in patients with low or negative index values. This discrepancy has a significant impact on clinical decision-making by both physicians and patients regarding natalizumab treatment in multiple sclerosis. Further investigations are warranted to assess the reliability and clinical relevance of these differences."

Clinical • CNS Disorders • Multiple Sclerosis

Safety and experiences with the natalizumab biosimilar in multiple sclerosis treatment (ECTRIMS 2025) - "While most patients perceived Tyruko as similar to Tysabri, some reported more side effects. However, this may be due to a nocebo effect, as this study was not blinded. Additionally, discrepancies in JCV results between the new ImmunoWELL assay and the STRATIFY assay complicate the clinical use of Tyruko."

Clinical • CNS Disorders • Multiple Sclerosis

Correlation of ImmunoWELL JCV IgG and STRATIFY JCV DxSelect for PML risk stratification using the anti-JCV-AK indices (ECTRIMS 2025) - "Objectives/Aims: Following the expiry of the patent for natalizumab (Tysabri, Biogen), the first biosimilar PB006 (TYRUKO®, Sandoz) has now been available since 2023 and, as the name biosimilar suggests, is not identical but very similar to the original preparation and can therefore be used without further safety concerns. The study demonstrates a high diagnostic accuracy of the ImmunoWELL JCV IgG test and leads to the conclusion, that it detects the JC virus equivalently to the STRATIFY DxSelect reference test in cases of infection."

CNS Disorders • Infectious Disease • Multiple Sclerosis

A comparison of JC virus assay performance provided with originator and biosimilar natalizumab. (PubMed, Mult Scler) - "These observed differences create uncertainty in how to counsel patients and best carry out PML surveillance. Specific concerns include overestimating risk leading to increased patient concern, increased monitoring burden and associated healthcare costs and lack of access to a highly effective therapy. It is incumbent on all stakeholders including pharmaceutical industry and test developers, patient groups, governmental authorities (including regulatory bodies) and clinicians to work together to find an expeditious solution."

Clinical • Journal • CNS Disorders • Multiple Sclerosis • Rare Diseases

Approach to JCV testing with natalizumab biosimilar: a UK consensus statement. (PubMed, Mult Scler Relat Disord) - "There remains a real risk that a proportion of patients will be inappropriately classified as being at higher risk of PML, and therefore denied the option of natalizumab, a highly effective therapy, or undergo unnecessarily burdensome monitoring, with resultant cost to the NHS and anxiety. We provide guidance for patients with discordant results between assays, aiming to balance the need for rigorous safety monitoring with patient access to highly effective therapy and unnecessary monitoring burden on healthcare services."

Journal • Review • CNS Disorders • Mood Disorders • Multiple Sclerosis • Psychiatry • Rare Diseases

Sandoz reports strong FY 2024 results and Q4 2024 sales (GlobeNewswire) - "Net sales for the fourth quarter were USD 769 million, up 25% in constant currencies. Net sales for the full year were USD 2.9 billion, up 30% in constant currencies. The biosimilars share of total net sales increased from 23% in FY 2023 to 28% in FY 2024. The strong double-digit biosimilars growth reflects the uptake of Hyrimoz in the US through the private- label agreement with...the Sandoz Hyrimoz and unbranded adalimumab-adaz. In addition...the continued strong demand for the first-ever biosimilar...and the launches of Tyruko and Pyzchiva in Europe all contributed to the strong performance."

Sales • Hidradenitis Suppurativa • Immunology • Inflammatory Bowel Disease • Ophthalmology • Rheumatoid Arthritis

MS patients suffer side-effects after NHS England switches to cheaper drug (Guardian) - "Scores of people with multiple sclerosis (MS) have suffered debilitating side-effects after being put on to a cheaper new drug as part of an NHS drive to save money...About 170 MS patients at Charing Cross hospital in London have had complications, including a relapse of their illness, after being switched from Tysabri to a different drug called Tyruko, made by the pharmaceutical company Sandoz....In a handful of cases, the people affected developed such serious symptoms that they had to be taken to hospital for treatment. Patients have told doctors about side-effects including an inability to use their legs, other mobility problems, fatigue, pain and sudden weight gain."

Commercial • Multiple Sclerosis

TREAT-MS: Traditional Versus Early Aggressive Therapy for Multiple Sclerosis Trial (clinicaltrials.gov) - P=N/A | N=900 | Active, not recruiting | Sponsor: Johns Hopkins University | Recruiting ➔ Active, not recruiting | Trial completion date: Aug 2025 ➔ Aug 2026 | Trial primary completion date: Aug 2025 ➔ Aug 2026

Enrollment closed • Trial completion date • Trial primary completion date • CNS Disorders • Multiple Sclerosis

Introducing the Biosimilar Paradigm to Neurology: The Totality of Evidence for the First Biosimilar Natalizumab. (PubMed, BioDrugs) - "This review presents the totality of evidence that confirmed the biosimilarity of biosimilar natalizumab to its reference medicine, which supported its approval by the FDA and the EMA. [Graphical plain language summary available]."

Journal • Review • CNS Disorders • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease • Multiple Sclerosis

Budget impact analysis of biosimilar natalizumab in the US. (PubMed, Am J Manag Care) - "Adoption of biosimilar NTZ can yield considerable cost savings to US health plans that could result in increased treatment access for patients with RRMS."

HEOR • Journal • CNS Disorders • Multiple Sclerosis

Cost-minimisation analysis of natalizumab biosimilar compared to reference natalizumab for multiple sclerosis (EAN 2024) - No abstract available

HEOR • CNS Disorders • Multiple Sclerosis

PB006: A Natalizumab Biosimilar. (PubMed, Clin Drug Investig) - "The tolerability, safety and immunogenicity profiles of PB006 were similar to those of reference natalizumab, and switching from reference natalizumab to PB006 appeared to have no impact on tolerability or immunogenicity. The role of reference natalizumab in the management of RRMS is well established and PB006 provides an effective biosimilar alternative for patients requiring natalizumab therapy."

Journal • Review • CNS Disorders • Multiple Sclerosis

Sandoz launches first and only biosimilar for multiple sclerosis, Tyruko (natalizumab), in Germany (Sandoz Press Release) - "Sandoz...today announces the launch of Tyruko (natalizumab) in Germany from February 1. Developed by Polpharma Biologics, Tyruko is the first and only biosimilar to treat RRMS....Under this agreement, Polpharma Biologics will maintain responsibility for development of medicine, manufacturing and supply of drug substance."

Biosimilar launch • Immunology • Multiple Sclerosis

Pharmacokinetic and pharmacodynamic similarity of biosimilar natalizumab (PB006) to its reference medicine. A randomized controlled trial. (PubMed, Expert Opin Biol Ther) - "Similarity was confirmed, with PB006 demonstrating PK/PD behavior consistent with that of ref-NTZ. EudraCT number 2019 -003,874-15."

Journal • PK/PD data • CNS Disorders • Multiple Sclerosis • CD34

MACE, VTE Risk Not Increased by Advanced Therapies for Inflammatory Bowel Disease (HCPLive) - "'The strength of this study is the large sample size, from healthcare organizations across the United States. Propensity score matching was used to control for variables that may impact MACE and VTE,' said Regueiro. 'This was a retrospective design, and it was a claim database, which means it does not provide granular detail on such things as disease severity, phenotype, behavior, and others.'"

Media quote

Sandoz receives European Commission approval for Tyruko (natalizumab), first and only biosimilar for multiple sclerosis in Europe (GlobeNewswire) - "Sandoz...announced that the European Commission (EC) granted marketing authorization for the first and only biosimilar Tyruko® (natalizumab), developed by Polpharma Biologics. The authorization covers treatment as a single disease-modifying therapy (DMT) in adults with highly active RRMS, the same indication as approved by the EC for the reference medicine Tysabri® (natalizumab)....The comprehensive regulatory submission package included evidence derived from an extensive analytical and functional characterization, in addition to results from a Phase I PK/PD study and a confirmatory Phase III Antelope study in RRMS patients."

European regulatory • Immunology • Multiple Sclerosis