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

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.'"

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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

FDA Approves First Biosimilar to Treat Multiple Sclerosis (PRNewswire) - "The U.S. Food and Drug Administration today approved Tyruko (natalizumab-sztn), the first biosimilar to Tysabri (natalizumab) injection for the treatment of adults with relapsing forms of multiple sclerosis (MS). Tyruko, like Tysabri, is also indicated for inducing and maintaining clinical response and remission in adult patients with moderately to severely active Crohn's Disease (CD) with evidence of inflammation who have had an inadequate response to, or are unable to tolerate, conventional CD therapies and inhibitors of TNF-α (tumor necrosis factor, a substance in your body that causes inflammation)."

BLA • Crohn's disease • Immunology • Inflammation • Inflammatory Bowel Disease • Multiple Sclerosis

Sandoz receives positive CHMP opinion for multiple sclerosis biosimilar natalizumab (GlobeNewswire) - "Sandoz...announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA), has adopted a positive opinion for marketing authorization for first-of-a-kind biosimilar natalizumab developed by Polpharma Biologics....The comprehensive analytical, preclinical, and clinical data regulatory submission package included evidence derived from an extensive analytical 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

The Totality of Evidence for Proposed Biosimilar Natalizumab PB006 Confirms Biosimilarity to Its Reference Medicine (CMSC 2023) - "The Totality of Evidence confirms biosimilarity of proposed biosimilar natalizumab PB006 to Ref-NTZ."

CNS Disorders • Multiple Sclerosis

Budget Impact Analysis of Transitioning from Reference to Biosimilar Natalizumab from a United States Payer Perspective (CMSC 2023) - "Adoption of a hypothetical biosimilar NTZ can result in considerable cost savings to the US health plans that may allow them to reinvest these cost savings to increase treatment access to patients with RRMS."

HEOR • CNS Disorders • Multiple Sclerosis

Biosimilar Equal to Natalizumab for Relapsing-Remitting MS (Medscape) - "'There will be a biosimilar that with respect to all parameters - efficacy, side effects, immunogenicity - doesn't differ from the original drug and will probably be an option to consider to reduce treatment costs in MS,' lead investigator Bernhard Hemmer, MD...told Medscape Medical News....At week 24, 30 patients were switched from ref-NTZ to biosim-NTZ for the remainder of their infusions. Including such a population is required by regulatory agencies to ensure switching patients from a drug they've been taking to a new biosimilar does not introduce any concerns, said Hemmer."

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First biosimilar monoclonal antibody for MS shown to be safe, effective in phase 3 trial (Healio) - "'PB006 is a biosimilar natalizumab (biosim-NTZ) and was developed by Polpharma Biologics SA as a proposed biosimilar to the reference natalizumab (ref-NTZ) in accordance with FDA and [European Medicines Agency] guidelines, which require biosimilars to match the reference medicine in analytical comparability, bioequivalence, safety, efficacy and immunogenicity, confirming no clinically relevant differences in performance across approved indications,' Bernhard Hemmer, MD...wrote....'The clinical efficacy, safety and immunogenicity of the proposed biosimilar natalizumab matched the reference natalizumab in the tested setting, with no clinically relevant differences observed,' Hemmer and colleagues wrote."

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Efficacy and Safety of Proposed Biosimilar Natalizumab (PB006) in Patients With Relapsing-Remitting Multiple Sclerosis: The Antelope Phase 3 Randomized Clinical Trial. (PubMed, JAMA Neurol) - P3 | "This phase 3 trial supports proposed biosim-NTZ as a biosimilar alternative to ref-NTZ for treating RRMS. ClinicalTrials.gov Identifier: NCT04115488."

Clinical • Journal • P3 data • CNS Disorders • Multiple Sclerosis

Göttingen pigs as a potential model for natalizumab pharmacokinetics, pharmacodynamics, and immunogenicity evaluation. (PubMed, Biomed Pharmacother) - "The presented study was conducted to explore the suitability of Göttingen pigs as a pharmacokinetic/pharmacodynamic model in the preclinical phase of biosimilar natalizumab development. All animals treated appeared to produce ADA. The concentrations of the ADA ranged from 15.8 to 16,748 ng/mL Göttingen pigs represent a suitable model for pharmacokinetic analysis and mechanism of action evaluation related to saturation of CD49d."

Journal • PK/PD data • ITGA4

Phase I PK/PD similarity study of proposed biosimilar natalizumab PB006: A single dose study in healthy individuals (EAN 2022) - No abstract available

Clinical • P1 data • PK/PD data

Effect of proposed biosimilar natalizumab on clinical endpoints in RRMS patients: Data from the Phase III Antelope study (EAN 2022) - No abstract available

Clinical • P3 data • Multiple Sclerosis

Effect of proposed biosimilar natalizumab on MRI endpoints in RRMS patients: Data from the Phase III Antelope study (EAN 2022) - No abstract available

Clinical • P3 data • Multiple Sclerosis

Antelope: Efficacy and Safety of the Biosimilar Natalizumab PB006 in Comparison to Tysabri® (clinicaltrials.gov) - P3 | N=265 | Completed | Sponsor: Polpharma Biologics S.A. | Active, not recruiting ➔ Completed | Trial completion date: Aug 2021 ➔ Feb 2022 | Trial primary completion date: Mar 2021 ➔ Aug 2021

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

Efficacy and safety of proposed natalizumab biosimilar PB006 versus Tysabri® in patients with relapsing remitting multiple sclerosis: Primary data from the Phase III Antelope study (AAN 2022) - P3 | "Analysis of the primary endpoint and safety data suggest that Biosim-NTZ matches Ref-NTZ for efficacy and safety. No new safety signals were observed in the Biosim-NTZ group."

Clinical • P3 data • CNS Disorders • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease • Multiple Sclerosis • Rare Diseases

Bernhard Hemmer, ECTRIMS 2021: Phase 3 Antelope Study Results Investigating Natalizumab Biosimilar PB006 in RMS (Touchneurology) - "touchNEUROLOGY met up with Prof. Bernhard Hemmer...to discuss the primary data from the phase III Antelope study, investigating proposed natalizumab biosimilar PB006 in relapsing remitting multiple sclerosis. The abstract entitled: 'Efficacy and safety of proposed natalizumab biosimilar PB006 versus Tysabri® in patients with relapsing remitting multiple sclerosis: primary data from the phase III Antelope study' was presented at the 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), 13-15 October 2021....Why are biosimilar drugs needed in MS and what are the challenges in their production? (0:17)...What will be the next step in the clinical development of biosimilar natalizumab? (2:02)."

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