TheraRadar
Data updated: May 26, 2026

TYSABRI (natalizumab)

Integrin Receptor Antagonists Trial Activity: Declining
Immunology Approved 2004-11-23

Tysabri (natalizumab) is an integrin receptor antagonist indicated as monotherapy for adults with relapsing forms of multiple sclerosis, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease. It is also used to induce and maintain clinical response and remission in adult patients with moderately to severely active Crohn's disease who show evidence of inflammation and have failed or cannot tolerate conventional therapies and TNF-α inhibitors. Because the drug increases the risk of progressive multifocal leukoencephalopathy (PML), physicians must determine if the expected benefits outweigh this risk. In the treatment of Crohn's disease, Tysabri must not be used in combination with other immunosuppressants or TNF-α inhibitors.

Source: FDA Label • Biogen • Integrin Receptor Antagonist

How TYSABRI Works

Natalizumab binds to the α4-subunit of α4β1 and α4β7 integrins expressed on the surface of most leukocytes, excluding neutrophils. This binding inhibits the adhesion of leukocytes to their receptors, such as VCAM-1 on the vascular endothelium and MAdCAM-1 in the gastrointestinal tract. By disrupting these molecular interactions, the drug prevents inflammatory cells from migrating across the endothelium into parenchymal tissue. In multiple sclerosis, this mechanism is believed to block activated inflammatory cells from crossing the blood-brain barrier, thereby reducing inflammatory activity in the brain.

Development Insights

Biogen conducting 16 trials (62%)
15 indications explored (Broad Platform)
multiple sclerosis (5 trials)
multiple sclerosis, relapsing-remitting (4 trials)
relapsing-remitting multiple sclerosis (4 trials)
6
Indications
--
Phase 3 Trials
2
Priority Reviews
21
Years on Market

Details

Status
Prescription
First Approved
2004-11-23
Patent Cliff
2027
Revenue
$398M (Q4-2025)

Pro Metrics

Patent cliff and revenue data

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Routes
SINGLE-USE
Dosage Forms
VIAL

Companies

Active Ingredient: NATALIZUMAB

TYSABRI Approval History

2005
2006
2007
2008
2009
2010
2011
2012
2013
2014
2015
2016
2017
2018
2019
2020
2021
2022
2023
2024
2025
2026
Original
New Indication
New Form
Label Update
39 FDA actions from 2004 to 2025 · 5 indication expansions
Mar 2025 SUPPL
Label · Labeling
Oct 2023 SUPPL
Label · Labeling
Oct 2023 SUPPL
Label · Labeling

What TYSABRI Treats

2 indications

TYSABRI is approved for 2 conditions since its original approval in 2004. These indications span multiple therapeutic areas including oncology, immunology, and more.

  • Relapsing forms of multiple sclerosis (clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease)
  • Moderately to severely active Crohn's disease
Source: FDA Label

TYSABRI Boxed Warning

PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY TYSABRI increases the risk of progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain that usually leads to death or severe disability. Risk factors for the development of PML include the presence of anti-JCV antibodies, duration of therapy, and prior use of immunosuppressants. These factors should be considered in the context of expected benefit when initiating and continuing treatment with TYSABRI [ see Warnings...

TYSABRI Biosimilars

1 FDA-approved

These 1 alternatives require prescriber approval to substitute for TYSABRI.

What are biosimilars? Lower-cost alternatives to TYSABRI with no clinically meaningful differences.

Auto-substitute OK = FDA "interchangeable" designation — pharmacist can switch without calling the doctor.

TYSABRI Competitive Set

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Three rings of competition based on shared molecular targets and treated indications.

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Filters applied: drops same-active-ingredient (505(b)(2) reformulations), route-mismatch (topical vs systemic), and cross-therapeutic-area matches in same-indication rings.

Drugs Similar to TYSABRI

FDA-approved drugs for similar conditions. Compare mechanisms and indications to understand treatment alternatives.

SKYRIZI
RISANKIZUMAB-RZAA
1 shared
AbbVie
Shared indications:
Moderately to severely active Crohn's disease
TREMFYA
GUSELKUMAB
1 shared
Johnson & Johnson
Shared indications:
Moderately to severely active Crohn's disease
ZEPOSIA
OZANIMOD HYDROCHLORIDE
1 shared
Bristol-Myers Squibb
Shared indications:
Relapsing forms of multiple sclerosis (clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease)
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Clinical Trial Registry

25 trials
Trial Sponsor ID Phase Status Title
NCT05265728 results posted 101MS330 Ph 3 terminated A Study to Evaluate Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of Natalizumab (BG00002) Administered Subcutaneously to Japanese Participants With Relapsing-Remitting Multiple Sclerosis
NCT05618301 202302190 Ph 1 completed Motixafortide and Natalizumab to Mobilize CD34+ Hematopoietic Stem Cells for Gene Therapies in Sickle Cell Disease (SCD)
NCT03046251 NAPPREMS results posted US-TYS-14-10720 Ph 4 completed Natalizumab in Preventing Post-partum Relapses in Multiple Sclerosis
NCT03811886 CASE1718 Ph 1, Ph 2 withdrawn Natalizumab in Recurrent, Refractory or Progressive Pulmonary Metastatic Osteosarcoma
NCT05532163 DE-TYS-12072 2022-001820-14 Ph 4 terminated A Study to Investigate the Radiological Onset of Action After Treatment Initiation With Subcutaneous (SC) Natalizumab in Participants With Relapsing-Remitting Multiple Sclerosis (RRMS)
NCT03689972 results posted 101MS329 2018-002145-11 Ph 3 completed A Study to Evaluate Efficacy, Safety, and Tolerability of EID of Natalizumab (BG00002) in Participants With RRMS Switching From Treatment With Natalizumab SID in Relation to Continued SID Treatment- Followed by Extension Study Comprising SC and IV Natalizumab Administration
NCT02142192 SIMPLIFY 101MS207 2014-000917-30 Ph 2 terminated Natalizumab Subcutaneous Immunogenicity and Safety Study
NCT03093064 IRIS 208083 Ph 1 completed Inflammatory Response In Schizophrenia
NCT02133924 results posted GCO 15-1624 Ph 2 completed Multicenter Study Of Natalizumab Plus Standard Steroid Treatment For High Risk Acute Graft-Versus-Host Disease
NCT03283371 OPUS results posted 101EP201 2017-001995-45 Ph 2 completed Phase 2 Efficacy, Safety, and Tolerability Study of Natalizumab in Focal Epilepsy
NCT02176031 results posted 14-140 Ph 2 completed Phase II Trial of Natalizumab + Prednisone for Initial Therapy of Acute GI GVHD
NCT03516526 PDNMS NL56584.029.16 Ph 4 completed Towards Personalized Dosing of Natalizumab in Multiple Sclerosis
NCT02730455 ACTION2 results posted 101SK202 2015-004783-11 Ph 2 completed Safety and Efficacy of Intravenous Natalizumab in Acute Ischemic Stroke
NCT01416181 ASCEND in SPMS results posted 101MS326 2010-021978-11 Ph 3 terminated A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Participants With Secondary Progressive Multiple Sclerosis
NCT02342704 REVEAL results posted 101MS408 2013-004622-29 Ph 4 terminated Impact of Natalizumab Versus Fingolimod in Relapsing-Remitting Multiple Sclerosis (RRMS) Participants
NCT02241785 ESCALATE results posted 101MS409 2013-005586-39 Ph 4 terminated Natalizumab as an Efficacy Switch in Participants With Relapsing Multiple Sclerosis After Failure on Other Therapies
NCT01955707 ACTION results posted 101SK201 EUDRA CT NO: 2013-001514-15 Ph 2 completed Effect of Natalizumab on Infarct Volume in Acute Ischemic Stroke
NCT01884935 101MS328 2012-005082-13 Ph 1 completed PK and PD Study of Natalizumab in Pediatric Subjects With RRMS
NCT00801125 ELN51-309-503 CD FACTOR Ph 4 withdrawn Study of Tysabri (Natalizumab) in Patients Who Failed Anti-TNF-α Therapy
NCT01416155 results posted 101MS204 Ph 2 completed Extension Study to Evaluate Safety and Efficacy of Natalizumab in Japanese Participants With Relapsing-Remitting Multiple Sclerosis
NCT00744679 101MS406 Ph 4 completed A Pharmacokinetic (PK) Study of Natalizumab (Tysabri) at Steady State
NCT01144052 results posted EOC.NC.09.01 Ph 4 completed Natalizumab De-escalation With Interferon Beta-1b
NCT01071083 RESTORE results posted 101MS205 Ph 2 completed Treatment Interruption of Natalizumab
NCT01077466 NAPMS NAPMS version 3.4 Ph 2 completed Natalizumab Treatment of Progressive Multiple Sclerosis
NCT00942214 Bionat2 0811001 Ph 4 completed Biomarkers and Response to Natalizumab for Multiple Sclerosis Treatment
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Active Pipeline

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Ongoing clinical trials by development phase

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Key Completed Trials

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Completed studies with published results, ranked by significance

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Trial Timeline

Full development history with FDA approval milestones

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Understanding FDA Approval Types
Count Type What it means
- ORIG Original approval - drug first enters market
- SUPPL - Efficacy New indication (new disease/condition approved)
- SUPPL - Labeling Label text changes (warnings, dosing updates)
- SUPPL - Manufacturing Production changes (new facility)
- SUPPL - Chemistry Formulation changes (new dosage strength)

Green lines in the timeline show ORIG and Efficacy approvals - the clinically meaningful milestones.

TYSABRI FDA Label Details

Indications & Usage

FDA Label (PDF)

TYSABRI is indicated for the treatment of Relapsing forms of multiple sclerosis (clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease); Moderately to severely active Crohn's disease.

⚠️ BOXED WARNING

WARNING: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY TYSABRI increases the risk of progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain that usually leads to death or severe disability. Risk factors for the development of PML include the presence of anti-JCV...

Pro Intelligence Preview

Deep insights for TYSABRI

Revenue Insights

  • Q4-2025: $398M
  • Historical trend analysis

Patent Timeline

  • Cliff: 2027
  • Generic/biosimilar risk

Trial Analysis

  • 26 total trials
  • Stage: Declining

Competitive Landscape

  • 3 similar drugs
  • Same target/indication analysis
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Full approval history • All patents • Revenue trends • Competitor analysis

Data Sources

Data sourced from official FDA and NIH databases. Click links to verify on original sources.

How We Calculate These Metrics

Trial Activity Stage

Measures the current development activity pattern based on trial phases, status, and trends. Important: This measures R&D activity, not commercial lifecycle.

Trial statuses: "Active" means recruiting or ongoing. "Completed" means reached planned endpoint. "Terminated" means stopped early—often due to safety, efficacy, or business reasons.

  • Growth: High proportion of early-phase trials (Phase 1/2), active development
  • Expansion: Significant Phase 3 activity, approaching or pursuing approvals
  • Mature: Substantial Phase 4 post-marketing studies
  • Stable: Mixed phase distribution, steady development
  • Declining: Low active trial ratio, reduced R&D investment