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Namilumab - Amgen/Izana Bioscience/Takeda

Drug Profile

Namilumab - Amgen/Izana Bioscience/Takeda

Alternative Names: AMG 203; Amg203; IZN 101; MT-203; MT03

Latest Information Update: 29 Apr 2020

At a glance

  • Originator Micromet Inc
  • Developer Izana Bioscience; Takeda Pharmaceuticals International GmbH
  • Class Anti-inflammatories; Antipsoriatics; Antirheumatics; Monoclonal antibodies
  • Mechanism of Action Granulocyte macrophage colony stimulating factor antagonists
  • Orphan Drug Status

    Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.

    No
  • New Molecular Entity Yes

Highest Development Phases

  • Phase II Ankylosing spondylitis
  • Clinical Phase Unknown COVID 2019 infections
  • Discontinued Plaque psoriasis; Rheumatoid arthritis

Most Recent Events

  • 06 Apr 2020 Clinical trials in COVID-2019 infections in Italy (Parenteral)
  • 06 Apr 2020 The regulatory body granted emergency access for COVID-2019 infections
  • 06 Apr 2020 Izana Bioscience plans a phase III trial in Rheumatoid arthritis (Izana Bioscience website - April 2020)

Development Overview

Introduction

Namilumab (IZN 101), a fully human antibody, is being developed by Amgen, Izana Bioscience and Takeda Pharmaceuticals International for the treatment of acute and chronic inflammatory and autoimmune diseases. Namilumab neutralises the activity of granulocyte macrophage colony stimulating factor (GM-CSF) by preventing GM-CSF from binding to high-affinity cell surface receptors and causing inflammatory reactions. Micromet, who originally developed the compound, believes that namilumab is one of the first human antibodies neutralising the biologic activity of human and non-human primate GM-CSF. Nifurtimox induces DNA damages in hypoxic tumour cells. Namilumab has potential in the treatment of rheumatoid arthritis, asthma, psoriasis, multiple sclerosis, ankylosing spondylitis, and chronic obstructive pulmonary disease. Clinical development of subcutaneous formulation for ankylosing spondylitis is underway in the UK. Namilumab is also under clinical development for the treatment of COVID-2019 infections under the compassionate use pathway in Italy. Phase II development was underway in patients with rheumatoid arthritis however, Takeda discontinued development of the product for this indication. Development of namilumab was discontinued for plaque psoriasis in Canada and the EU, because a phase II trial did not meet its primary endpoint.

In September 2011, Takeda acquired Nycomed and subsequently renamed it as Takeda Pharmaceuticals International GmbH [1] .

In March 2012, Amgen acquired Micromet [2] .

Company Agreements

In December 2017, Izana Bioscience entered into an exclusive worldwide licence agreement with Takeda for the right to develop, manufacture and commercialise namilumab in all indications, further to its right to sublicense under its licence agreement with Amgen. As part of the licence agreement, Takeda has taken a strategic equity stake in Izana. Earlier, in May 2007, Micromet entered into a collaboration and licensing agreement with Nycomed (now Takeda), for the development of namilumab. Under the terms of the agreement, Micromet has conducted preclinical development of the antibody, and Takeda will be responsible for clinical development and commercialisation. Micromet received an upfront license fee of $US7 million, and research and development reimbursements and milestone payments owing to Amgen may total over $US160 million. Amgen will receive royalties on worldwide sales of namilumab, and development will be funded by Takeda. [3] [4] [5]

Key Development Milestones

Active indication:

Ankylosing-spondylitis

In February 2020 , Izana Bioscience completed the phase II NAMASTE trial which evaluated the efficacy of namilumab, in patients with moderate-to-severely active axial spondyloarthritis, including those previously exposed to anti-TNF therapy (IZN101; EudraCT2018-000176-15; NCT03622658). Evaluation of the proportion of subjects who achieve an ASAS20 clinical response, at week 12, was the defined primary endpoint of the trial. The randomised, double blind trial, which was initiated in June 2018, enrolled 42 patients in the UK [6] .

COVID-2019 infections

In April 2020, Izana Bioscience announced that it is providing support for a clinical development programme for namilumab, for the treatment of patients with rapidly worsening COVID-2019 infections in Italy, under the compassionate use pathway. The comapany also reported that the therapy granted emergency access. The company is in discussions with other global regulatory authorities, including the UK, for further development of namilumab for the treatment of COVID-2019 infections [7] [8] .

Discontinued indications:

Rheumatoid arthritis

In May 2017, Takeda reported that it had stopped clinical development of namilumab for the treatment of patients with rheumatoid arthritis. The decision was based on strategic alignment reasons, and the product will be pivoted to external value creation (Takeda pipeline, May 2018). Phase II development was underway for rheumatoid arthritis in Japan (Takeda pipeline, February 2016).

In November 2016, Takeda terminated the phase II TELLUS trial as per the strategic decision to understand data from psoriasis study NCT02129777 [see below] and to wait for results of formal proof of concept study NCT02379091 [see below] (15SC0020; MT203-2004; REec-2015-1508; U1111-1165-2221; NCT02393378; EudraCT2014-002945-23). The trial was initiated in April 2015 to evaluate the efficacy of subcutaneous namilumab compared with adalimumab (both in combination with methotrexate), in patients with moderate to severe early rheumatoid arthritis who have showed an inadequate response to prior methotrexate therapy. The open-label trial enrolled seven patients in Czech Republic, Estonia, Spain, Russia and the UK [9] .

In November 2016, Takeda completed the phase II NEXUS trial which evaluated the safety and efficacy of three dose levels of subcutaneous namilumab (20, 80 and 150 mg), in combination with methotrexate, in patients with moderate to severe rheumatoid arthritis who showed inadequate response following treatment with methotrexate and a TNF-inhibitor (JapicCTI-152979; NCT02379091; EudraCT2013-002805-76). The primary endpoint was the change from baseline in disease activity, assessed at week 12. The randomised, parallel-assignment trial initiated in November 2014, enrolled 108 patients in the UK, Bulgaria, Japan, Czech, South Korea, Poland, Russia and Spain [10] .

A randomised, double-blind, placebo-controlled phase Ib trial was completed in Bulgaria and the Netherlands in patients with mild to moderate rheumatoid arthritis who were receiving methotrexate (PRIORA; NCT01317797). The trial evaluated the safety and tolerability of subcutaneous injections of namilumab, compared with placebo, in 24 patients. Pharmacokinetics, biomarkers and preliminary efficacy were also assessed [11] .

Takeda initiated a phase I trial in November 2014, to investigate the safety, pharmacokinetics and pharmacodynamics of a single subcutaneous injection of namilumab in healthy volunteers (NCT02354599). Approximately 32 volunteers in Japan will be randomised to receive namilumab (80mg, 150mg or 300mg) or placebo [12] .

Nycomed initiated a randomised, double-blind, placebo-controlled phase I trial in June 2009 to evaluate the safety and pharmacokinetics of namilumab [3] [13] . In April 2009, Nycomed filed the first Clinical Trial Application for namilumab, in Europe. Micromet received $US2 million from Nycomed for this milestone [14] .

Micromet initiated preclinical safety studies of namilumab in June 2008. As a result, Micromet received a milestone payment of $US 775 000 from Nycomed [15] .

Plaque psoriasis

As of May 2017, Takeda discontinued development of namilumab for plaque psoriasis in Latvia, Poland, Germany, Denmark, and Canada, because a phase II trial did not meet its primary endpoint (Takeda FY2016 Q4 results, May 2017).

Takeda terminated a randomised, double-blind, placebo-controlled phase II trial, that was designed to evaluate the efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics of four dose levels of namilumab in patients with moderate to severe plaque psoriasis; the study was initiated in May 2014 (Neptune; NCT02129777; EudraCT2013-002806-30; U1111-1146-1219; 172235; M1-1188-203). Patients were to be dosed on days 1, 15, 43 and 71, and the primary endpoint was the percentage of patients achieving an improvement in PASI 75 at week 12. The trial was expected to enrol approximately 122 patients in Germany, Denmark, Poland, Latvia and Canada [16] .

Financing information

Izana Bioscience, in December 2017, announced the award of a grant of £1.35 million by Innovate UK, to support a phase II proof-of-concept study in ankylosing spondylitis [5] .

Drug Properties & Chemical Synopsis

  • Route of administration Parenteral, SC
  • Formulation Injection, unspecified
  • Class Anti-inflammatories, Antipsoriatics, Antirheumatics, Monoclonal antibodies
  • Target Granulocyte macrophage colony stimulating factor
  • Mechanism of Action Granulocyte macrophage colony stimulating factor antagonists
  • WHO ATC code

    D05B-X (Other antipsoriatics for systemic use)

    L04A (Immunosuppressants)

    M01 (Antiinflammatory and Antirheumatic Products)

  • EPhMRA code

    D5B (Systemic Antipsoriasis Products)

    L4X (Other Immunosuppressants)

    M1 (Anti-Inflammatory and Anti-Rheumatic Products)

  • CAS Registry Number 1206681-39-1

Biomarkers Sourced From Trials

Indication Biomarker Function Biomarker Name Number of Trials

rheumatoid arthritis

Inclusion

CRP

2

rheumatoid arthritis

Outcome Measure

Tau protein

GM-CSF

gamma-glutamyltransferase light chain 1

CRP

bestrophin 1

1

1

1

2

1

Biomarker

Drug Name Biomarker Name Biomarker Function
Namilumab - Amgen/Izana Bioscience/Takeda bestrophin 1 Outcome Measure
CRP Inclusion, Outcome Measure
gamma-glutamyltransferase light chain 1 Outcome Measure
GM-CSF Outcome Measure
Tau protein Outcome Measure
For more detail, check out BiomarkerBase: the leading source of information about biomarkers used in drug development and diagnostic tests, tracking a comprehensive list of biomarker uses worldwide by over 800 companies

Development Status

Summary Table

Indication Qualifier Patient Segment Phase Countries Route / Formulation Developers Event Date
Ankylosing spondylitis - Treatment-experienced Phase II United Kingdom SC / Injection Izana Bioscience 19 Jun 2018
COVID 2019 infections under compassionate use - Clinical Phase Unknown Italy Parenteral / unspecified Izana Bioscience 06 Apr 2020
Plaque psoriasis - In adults, In the elderly Discontinued (II) Canada, Denmark, Germany, Latvia, Poland SC / Injection Takeda Pharmaceuticals International GmbH 10 May 2017
Rheumatoid arthritis - - Discontinued (II) Japan SC / Injection Takeda Pharmaceuticals International GmbH 10 May 2017
Rheumatoid arthritis - Combination therapy, In adults, In the elderly Discontinued (II) Bulgaria, Czech Republic, Poland, Russia, South Korea, Spain, United Kingdom SC / Injection Takeda Pharmaceuticals International GmbH 10 May 2017
Rheumatoid arthritis - - Discontinued (I) Bulgaria, Netherlands, USA SC / Injection Takeda Pharmaceuticals International GmbH 10 May 2017

Commercial Information

Involved Organisations

Organisation Involvement Countries
Micromet Inc Originator USA
Amgen Owner USA
Takeda Pharmaceuticals International GmbH Licensee Switzerland
Izana Bioscience Sub-licensee World

Credit Suisse Market Status

Indication Region Company Phase Expected Launch Year Probability of Success% Patent Expiry Year Expected Generic Entry Last Update
RA ex US - II 2021 10 - - 02 Apr 2020

Development History

Event Date Update Type Comment
06 Apr 2020 Phase Change - Clinical Clinical trials in COVID-2019 infections in Italy (Parenteral) [8] Updated 09 Apr 2020
06 Apr 2020 Regulatory Status The regulatory body granted emergency access for COVID-2019 infections [8] Updated 09 Apr 2020
06 Apr 2020 Trial Update Izana Bioscience plans a phase III trial in Rheumatoid arthritis [7] (Izana Bioscience website - April 2020) Updated 09 Apr 2020
02 Apr 2020 Financial Update Credit Suisse financial data update Updated 11 Apr 2020
04 Feb 2020 Trial Update Izana Bioscience completes the phase III NAMASTE trial in Ankylosing spondylitis (Treatment-experienced) in United Kingdom (SC) (NCT03622658) (EudraCT2018-000176-15) Updated 29 Apr 2020
24 Jun 2018 Biomarker Update Biomarkers information updated Updated 31 Aug 2018
19 Jun 2018 Phase Change - II Phase-II clinical trials in Ankylosing spondylitis (Treatment-experienced) in United Kingdom (SC) (EudraCT2018-000176-15) (NCT03622658) Updated 19 Jul 2018
20 Dec 2017 Trial Update Izana Bioscience plans a phase II trial in Ankylosing spondylitis [5] Updated 20 Dec 2017
14 Dec 2017 Licensing Status Namilumab licensed to Izana Bioscience worldwide [5] Updated 20 Dec 2017
10 May 2017 Phase Change - Discontinued(I) Discontinued - Phase-I for Rheumatoid arthritis in Bulgaria, Netherlands, USA (SC) (Takeda pipeline, May 2018) Updated 28 Aug 2018
10 May 2017 Phase Change - Discontinued(II) Discontinued - Phase-II for Rheumatoid arthritis (Combination therapy, In the elderly, In adults) in South Korea, Russia (SC), Bulgaria, Czech Republic, United Kingdom, Poland, Spain (SC) (Takeda pipeline, May 2018) Updated 21 May 2018
10 May 2017 Phase Change - Discontinued(II) Discontinued - Phase-II for Rheumatoid arthritis in Japan (SC) (Takeda pipeline, May 2018) Updated 21 May 2018
10 May 2017 Phase Change - Discontinued(II) Discontinued - Phase-II for Plaque psoriasis (In the elderly, In adults) in Latvia, Poland, Germany, Denmark, and Canada (SC) because a phase II trial did not meet its primary endpoint (Takeda FY2016 Q4 results, May 2017) Updated 16 Jun 2017
16 Nov 2016 Trial Update Takeda terminates the TELLUS phase II trial for Rheumatoid arthritis (Combination therapy, In the elderly, In adults) in Russia, Czech Republic, Estonia and Spain and the United Kingdom (SC) (NCT02393378) Updated 19 Feb 2019
01 Nov 2016 Trial Update Takeda completes the NEXUS trial in Rheumatoid arthritis (Combination therapy, In the elderly, In adults) in Bulgaria, Czech Republic, Japan, South Korea, Russia, Spain and United Kingdom (SC) (NCT02379091) Updated 16 Feb 2017
16 Jul 2016 Phase Change - No development reported No recent reports of development identified for phase-I development in Rheumatoid-arthritis in Bulgaria (SC, Injection) Updated 16 Jul 2016
16 Jul 2016 Phase Change - No development reported No recent reports of development identified for phase-I development in Rheumatoid-arthritis in Netherlands (SC, Injection) Updated 16 Jul 2016
16 Jul 2016 Phase Change - No development reported No recent reports of development identified for phase-I development in Rheumatoid-arthritis in USA (SC, Injection) Updated 16 Jul 2016
31 Dec 2015 Phase Change - II Phase-II clinical trials in Rheumatoid arthritis (Combination therapy, In adults, In the elderly) in Japan before December 2015 (SC) (NCT02379091) Updated 17 Feb 2016
22 Sep 2015 Trial Update Takeda terminates a phase II trial in Plaque psoriasis (In adults, In the elderly) in Canada, Denmark, Germany, Latvia and Poland (EudraCT2013-002806-30) Updated 08 Mar 2016
08 Apr 2015 Trial Update Takeda initiates enrolment in a phase II trial for Rheumatoid arthritis (Combination therapy, In the elderly, In adults) in Russia (SC) (NCT02393378) Updated 19 Feb 2019
01 Feb 2015 Phase Change - II Phase-II clinical trials in Rheumatoid arthritis (Combination therapy, In adults, In the elderly) in South Korea (SC) (NCT02379091) Updated 16 Feb 2017
01 Feb 2015 Phase Change - II Phase-II clinical trials in Rheumatoid arthritis (Combination therapy, In the elderly, In adults) in Czech Republic (SC) (NCT023790910) Updated 31 Dec 2015
16 Dec 2014 Phase Change - II Phase-II clinical trials in Rheumatoid arthritis (Combination therapy, In the elderly, In adults) in United Kingdom (SC) (EudraCT2014-002945-23) Updated 08 Feb 2017
16 Dec 2014 Trial Update Takeda initiates enrolment in the TELLUS trial for Rheumatoid arthritis (Combination therapy, In elderly, In adults) in Czech Republic and Spain after December 2014 (EudraCT2014-002945-23) Updated 07 Feb 2017
30 Nov 2014 Phase Change - I Phase-I clinical trials in Rheumatoid arthritis (In volunteers) in Japan (SC) Updated 06 Feb 2015
06 Nov 2014 Phase Change - II Phase-II clinical trials in Rheumatoid arthritis (Combination therapy, In the elderly, In adults) in Russia, Poland (SC) (NCT02379091) Updated 16 Feb 2017
06 Nov 2014 Phase Change - II Phase-II clinical trials in Rheumatoid arthritis (Combination therapy, In the elderly, In adults) in Bulgaria (SC) after November 2014 Updated 25 Aug 2015
06 Nov 2014 Phase Change - II Phase-II clinical trials in Rheumatoid arthritis (Combination therapy, In adults, In the elderly) in Spain (SC) Updated 18 Nov 2014
08 May 2014 Phase Change - II Phase-II clinical trials in Plaque psoriasis (In adults, In the elderly) in Germany, Denmark, Poland, Latvia & Canada (SC) Updated 09 May 2014
20 Aug 2013 Trial Update Takeda completes the phase I PRIORA trial in Rheumatoid arthritis in Bulgaria and the Netherlands (NCT01317797) Updated 27 Aug 2013
30 Mar 2012 Company Involvement Nycomed is now called Takeda Pharmaceuticals International GmbH Updated 30 Mar 2012
07 Mar 2012 Company Involvement Micromet Inc has been acquired by Amgen Updated 09 Mar 2012
01 Feb 2012 Phase Change - I Phase-I clinical trials in Rheumatoid arthritis in USA (SC) Updated 21 Mar 2012
30 Sep 2011 Company Involvement Nycomed has been acquired by Takeda Updated 04 Oct 2011
28 Feb 2011 Phase Change - I Phase-I clinical trials in Rheumatoid arthritis in Bulgaria (SC) Updated 30 Mar 2011
28 Feb 2011 Phase Change - I Phase-I clinical trials in Rheumatoid arthritis in Netherlands (SC) Updated 30 Mar 2011
18 Jun 2009 Phase Change - I Phase-I clinical trials in Autoimmune disorders in Switzerland (Parenteral) Updated 22 Jun 2009
18 Jun 2009 Phase Change - I Phase-I clinical trials in Inflammation in Switzerland (Parenteral) Updated 22 Jun 2009
24 Jun 2008 Phase Change - Preclinical Preclinical trials in Autoimmune disorders in Germany (Parenteral) Updated 22 Jun 2009
24 Jun 2008 Phase Change - Preclinical Preclinical trials in Inflammation in Germany (Parenteral) Updated 22 Jun 2009

References

  1. Takeda Completes Acquisition and Names New CEO of Nycomed.

    Media Release
  2. Amgen Completes Tender Offer for Outstanding Shares of Micromet, Inc.

    Media Release
  3. Phase 1 Study Initiated with Micromet Anti-GM-CS Human Antibody MT203.

    Media Release
  4. Nycomed and Micromet Enter Into Exclusive Worldwide Collaboration to Develop and Commercialize anti-GM-CSF Antibodies for the Treatment of Inflammatory and Autoimmune Diseases.

    Media Release
  5. Izana Bioscience Launches as New Clinical-Stage Translational Medicine Company Developing Namilumab in Ankylosing Spondylitis.

    Media Release
  6. A phase 2a proof of concept, randomised, double-blind, placebo-controlled study to evaluate the safety/tolerability and efficacy of 4 subcutaneous injections of namilumab (150 mg) given over 10 weeks in subjects with moderate-to-severely active axial spondyloarthritis including those previously exposed to anti-TNF therapy (NAMASTE study)

    ctiprofile
  7. Izana Bioscience: Initiation of two-centre compassionate use study involving namilumab in the treatment of individual patients with rapidly worsening COVID-19 infection in Italy.

    Media Release
  8. Ergomed Announces Provision of Clinical Research Services for Second COVID-19 Clinical Development Programme.

    Media Release
  9. A 24-week Randomized, Open-Label, Parallel-Group, Active-Controlled, Exploratory, Proof-of-Mechanism Imaging Study Investigating the Efficacy of 150 mg of Namilumab Administered Subcutaneously vs Adalimumab in Patients With Moderate to Severe Early Rheumatoid Arthritis Inadequately Responding to Methotrexate

    ctiprofile
  10. A 24-Week Randomized, Double-Blind, Placebo-Controlled, Phase 2 Dose Finding Study to Evaluate the Efficacy and Safety of 3 Doses of Namilumab (20 mg, 80 mg and 150 mg) in Combination With Methotrexate (MTX) in Subjects With Moderate to Severe Rheumatoid Arthritis (RA)

    ctiprofile
  11. A Phase Ib Double-blind, Placebo-controlled, Randomized, Dose-escalating Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of Repeated Subcutaneous Injections of MT203 in Patients With Mild to Moderate Rheumatoid Arthritis on Treatment With Methotrexate.

    ctiprofile
  12. A Randomized, Single-center, Double-Blind, Placebo-Controlled Phase 1 Study to Evaluate Safety and Pharmacokinetics of Single Subcutaneous Injection of MT203 in Healthy Adult Japanese and Caucasian Male Participants

    ctiprofile
  13. Clinical Trials Insight: 700033898

    ctiprofile
  14. Micromet Receives Milestone Payment for Filing of the First Clinical Trial Application for MT203.

    Media Release
  15. Micromet and Nycomed Begin Formal Preclinical Safety Studies for Antibody MT203 for Inflammatory and Autoimmune Diseases.

    Media Release
  16. A Multi-Centre, Randomized, Double-Blind, Placebo-Controlled, Dose-Finding and Proof of Concept Study, to Assess the Efficacy, Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of Namilumab/MT203 at 4 Different Subcutaneous Doses - Together With an Open-Label, Dose-Escalated Extension to Assess Safety and Efficacy of One Year Treatment - in Subjects With Moderate to Severe Chronic Plaque Psoriasis

    ctiprofile
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