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Niclosamide - UNION Therapeutics

Drug Profile

Niclosamide - UNION Therapeutics

Alternative Names: ATx 201 - UNION Therapeutics; ATx201 OINTMENT - UNION Therapeutics; UNI-911

Latest Information Update: 07 Apr 2020

At a glance

  • Originator AntibioTx
  • Developer Institut Pasteur Korea; UNION Therapeutics
  • Class Anthelmintics; Antibacterials; Antineoplastics; Antivirals; Skin disorder therapies; Small molecules
  • Mechanism of Action Mitochondrial oxidative phosphorylation uncouplers; MTOR protein inhibitors; Notch signalling pathway inhibitors; STAT3 transcription factor inhibitors
  • Orphan Drug Status

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

    No
  • New Molecular Entity No

Highest Development Phases

  • Phase II Atopic dermatitis; Impetigo
  • Phase I/II Eczema
  • Phase I Unspecified
  • Preclinical COVID 2019 infections

Most Recent Events

  • 02 Apr 2020 UNION Therapeutics and Institut Pasteur Korea collaborate to develop niclosamide for COVID-2019 infections
  • 02 Apr 2020 UNION therapeutics plans to make submissions to Danish Medical authorities
  • 02 Apr 2020 UNION Therapeutics plans clinical trials for COVID-2019 infections

Development Overview

Introduction

ATx 201, is a niclosamide salt, being developed by UNION Therapeutics (formerly AntibioTx), for the treatment of impetigo, infected eczema and infected atopic dermatitis, caused by Staphylococcus aureus and some species of Streptococcus. The drug is also being developed for the potential treatment of COVID-2019 infections caused due to coronavirus (SARS-Cov-2) Clinical development is underway for atopic dermatitis, eczema, impetigo and an undefined indication in Canada, South Africa, Denmark, Austria and the US. Preclinical development for COVID-19 infections is underway in Denmark.

This profile has emerged from AntiBiotx' anti-infectives research programme [see AdisInsight drug profile 800044197].

In October 2018, AntibioTx changed its name to UNION Therapeutics [1] .

Company Agreements

In, April 2020, Union Therapeutics collaborated with Institut Pasteur Korea to test an optimised salt form of niclosamide as a treatment of COVID-19 infections. [2]

Key Development Milestones

Atopic dermatitis

UNION Therapeutics initiated a phase IIb trial in July 2019, to assess the safety and efficacy of topical niclosamide, in adolescents and adult patients, aged 12 years and older, with mild to moderate atopic dermatitis (EudraCT2019-002771-33; ATX201-207). The randomised, double-blind, dose-ranging trial intends to enrol approximately 210 patients in Denmark, and plans to expand the trial in three countries in the EU. In November 2019, the company reported the first patient first visit in the study [3] [4] .

In March 2018, AntibioTx completed a phase II trial to evaluate the safety and efficacy of niclosamide in patients with atopic dermatitis (ATx201-003; NCT03304470). This three-week, double-blind, randomised, two-arm, vehicle controlled trial was initiated in September 2017 and enrolled 31 patients in Canada [5] . In December 2018, UNION Therapeutics released positive results from the phase II trial. Niclosamide exhibited broad anti-inflammatory effect on various biomarkers affecting core elements of atopic dermatitis pathology [6] .
In March 2018, AntibioTx completed a phase I trial that evaluated the sensitisation potential of niclosamide topical gel (2% and 4%) in healthy volunteers (ATx201-005; NCT03375957). The randomised, single-blind trial was initiated in January 2018 and enrolled 240 participants in the US [7] . In October 2018, UNION Therapeutics released positive results from the phase I trial, which complements data from earlier trials in animals and humans and supports safety and tolerability of niclosamide in healthy and abraded skin [8] .

In November 2017, AntibioTx completed a phase I trial that evaluated the irritation potential of niclosamide topical 2% and 4% gel in healthy volunteers on intact and abraded skin (NCT03301870; ATx201-006). The double-blind, parallel, prospective, randomised trial was initiated in October 2017 and enrolled 36 healthy volunteers in the US [9] .

In March 2018, AntibioTx and Medical University of Vienna completed the phase II portion of a phase I/II trial that was evaluating the safety and efficacy of niclosamide 2% topical gel, in the treatment of skin infections of Staphylococcus aureus and Streptococcus, including eczema and atopic dermatitis (DECOLAD; EudraCT2016-003501-33; NCT03009734). The trial was initiated in December 2016 and phase I portion was completed in April 2017. The primary endpoint of the phase I part was to evaluate the tolerability of three formulations of the therapy in healthy volunteers. The best suited formulation was advanced to the phase II portion, which included patients with barrier impaired skin. The randomised, double blind, placebo-controlled trial enrolled 73 adults, including healthy volunteers in the phase I portion and patients in the phase II portion, in Austria [10] [11] . Earlier, in September 2016, AntibioTx had submitted a clinical trial application (CTA) to the Austrian Agency for Health and Food Safety, to initiate the study [12] [13] [14] . In December 2018, UNION Therapeutics released positive results from the phase II portion of the trial [6] .

In September 2016, AntibioTx reported that a 28-day repeat dosing, initiated in May 2016, of ATx201 in Göttingen pigs was found to be well tolerated with positive PK data and very low systemic exposure, and no genotoxicity was observed [15] [16] [17] . In December 2015, the company initiated a 28-day dermal toxicity study of ATx201 in Hanford Miniature Swine [18] .

COVID-2019 infections

As of April 2020, IND enabling studies are underway in Denmark for treatment of COVID-2019 infections (Union Therapeutics pipeline, April 2020) [2] .

Impetigo

In June 2018, AntibioTx completed a phase II trial that evaluated the safety, tolerability, systemic exposure, and activity of topical niclosamide gel (2% and 4%) treatment for 1, 2, or 5 days in outpatients with primary nonbullous or bullous impetigo (ATx201-004; NCT03429595). Evaluation of the incidences of adverse events reports and changes in significant laboratory parameters was the primary endpoint of the trial. The randomised, double blind, placebo control trial was initiated in February 2018, and enrolled 210 patients in South Africa [19] .

Patent Information

In May 2016, European Patent Office recognised primary claims of niclosamide topical gel, as novel and inventive. Earlier, in March 2016, two additional patents were filed for niclosamide topical gel [20] [21] .

Drug Properties & Chemical Synopsis

  • Route of administration Topical
  • Formulation Gel, unspecified
  • Class Anthelmintics, Antibacterials, Antineoplastics, Antivirals, Skin disorder therapies, Small molecules
  • Target MTOR protein; Notch signalling pathway; STAT3 transcription factor
  • Mechanism of Action Mitochondrial oxidative phosphorylation uncouplers; MTOR protein inhibitors; Notch signalling pathway inhibitors; STAT3 transcription factor inhibitors
  • WHO ATC code

    D11A (Other Dermatological Preparations)

    J05A-X (Other antivirals)

  • EPhMRA code

    D11 (Other Dermatological Preparations)

    J5B9 (Antivirals, others)

  • Chemical name 5-chloro-N-(2-chloro-4-nitrophenyl)-2-hydroxybenzamide
  • Molecular formula C13 H8 CL2 N2 O4
  • Chemical Structure
  • CAS Registry Number 50-65-7

Development Status

Summary Table

Indication Qualifier Patient Segment Phase Countries Route / Formulation Developers Event Date
Atopic dermatitis - - Phase II Canada Topical / Gel UNION Therapeutics 25 Sep 2017
Atopic dermatitis - In adolescents, In adults, In the elderly Phase II Denmark Topical / Gel UNION Therapeutics 17 Jul 2019
Atopic dermatitis - - Phase I/II Austria Topical / Gel UNION Therapeutics 01 Dec 2016
COVID 2019 infections - - Preclinical Denmark unspecified / unspecified Institut Pasteur Korea, UNION Therapeutics 02 Apr 2020
Eczema - - Phase I/II Austria Topical / Gel UNION Therapeutics 01 Dec 2016
Impetigo - In adolescents, In adults, In children, In infants, In the elderly Phase II South Africa Topical / Gel UNION Therapeutics 23 Feb 2018
Unspecified - In volunteers Phase I USA Topical / Gel UNION Therapeutics 04 Oct 2017

Commercial Information

Involved Organisations

Organisation Involvement Countries
AntibioTx Originator Europe
UNION Therapeutics Owner Denmark
Institut Pasteur Korea Collaborator South-Korea

Scientific Summary

Adverse Events

Atopic dermatitis

Phase I: Data from the phase I trial indicated that niclosamide was safe and well tolerated with no signs of sensitisation and no unexpected adverse events in the active group in comparison with the placebo group. The randomised and placebo-controlled phase I trial enrolled 240 healthy volunteers [8] [7] .

Therapeutic Trials

Atopic dermatitis

Phase II: Data from the phase II trial indciated that niclosamide successfully declononised Staphylococcus aureus from the lesions of 36 patients with atopic dermatitis. Niclosamide also restored healthy skin microbes and increased the microbial diversity on the skin [6] [14] .

Future Events

Expected Date Event Type Description Updated
28 Feb 2018 Trial Update AntibioTx plans a phase II trial for Impetigo in South Africa (700293068), (NCT03429595) 12 Mar 2018
01 Jan 2018 Trial Update AntibioTx plans a phase I trial in Healthy volunteers in USA (NCT03375957) (700291587) 02 Feb 2018
31 Oct 2017 Trial Update AntibioTx plans a phase I trial in Healthy volunteers in USA (NCT03301870) 07 Dec 2017

Development History

Event Date Update Type Comment
02 Apr 2020 Licensing Status UNION Therapeutics and Institut Pasteur Korea collaborate to develop niclosamide for COVID-2019 infections [2] Updated 07 Apr 2020
02 Apr 2020 Phase Change - Preclinical Preclinical trials in COVID-2019 infections in Denmark (unspecified route) before April 2020 [2] Updated 07 Apr 2020
02 Apr 2020 Regulatory Status UNION therapeutics plans to make submissions to Danish Medical authorities [2] Updated 07 Apr 2020
02 Apr 2020 Trial Update UNION Therapeutics plans clinical trials for COVID-2019 infections [2] Updated 07 Apr 2020
17 Jul 2019 Phase Change - II Phase-II clinical trials in Atopic dermatitis (In adolescents, In adults, In the elderly) in Denmark (Topical) (EudraCT2019-002771-33) Updated 09 Sep 2019
17 Jul 2019 Trial Update UNION Therapeutics plans a phase II trial in Atopic dermatitis (In adolescents, In adults) in Denmark (Topical, Ointment) (EudraCT2019-002771-33) Updated 21 Aug 2019
19 Dec 2018 Scientific Update Efficacy data from a phase II trial in atopic dermatitis released by UNION Therapeutics [6] Updated 21 Aug 2019
29 Oct 2018 Scientific Update Adverse events data from a phase I trial in Atopic dermatitis released by UNION Therapeutics [8] Updated 21 Aug 2019
05 Oct 2018 Company Involvement AntibioTx is now called UNION Therapeutics Updated 20 Aug 2019
26 Jun 2018 Trial Update AntibioTx completes a phase II trial in Impetigo (In adolescents, In adults, In children, In infants, In the elderly) in South Africa (Topical) (NCT03429595) Updated 13 Aug 2018
15 Mar 2018 Trial Update AntibioTx completes a phase I trial in Healthy volunteers in USA (Topical) (NCT03375957) Updated 24 May 2018
08 Mar 2018 Trial Update AntibioTx completes a phase-II clinical trial in Atopic dermatitis in Canada (Topical) (NCT03304470) Updated 28 Mar 2018
01 Mar 2018 Trial Update AntibioTx completes a phase I/II clinical trial in Eczema in Austria (Topical) (EudraCT2016-003501-33) Updated 27 Mar 2018
23 Feb 2018 Phase Change - II Phase-II clinical trials in Impetigo (In adolescents, In adults, In children, In infants, In the elderly) in South Africa (Topical) (NCT03429595) Updated 12 Mar 2018
12 Feb 2018 Trial Update AntibioTx plans a phase II trial for Impetigo in South Africa , (NCT03429595) Updated 12 Mar 2018
08 Jan 2018 Trial Update AntibioTx initiates a phase I trial in Healthy volunteers in USA (Topical) (NCT03375957) Updated 02 Feb 2018
18 Dec 2017 Trial Update AntibioTx plans a phase I trial in Healthy volunteers in USA (NCT03375957) Updated 02 Feb 2018
06 Nov 2017 Trial Update AntibioTx completes a phase I trial in an Undefined indication (In volunteers) in USA (Topical) (NCT03301870) Updated 07 Dec 2017
09 Oct 2017 Trial Update AntibioTx plans a phase I trial in Healthy volunteers in USA (NCT03301870) Updated 07 Dec 2017
04 Oct 2017 Phase Change - I Phase-I clinical trials in an Undefined indication (In volunteers) in USA (Topical) (NCT03301870) Updated 07 Dec 2017
25 Sep 2017 Phase Change - II Phase-II clinical trials in Atopic dermatitis in Canada (Topical) (NCT03304470) Updated 12 Oct 2017
23 Jan 2017 Other Chemical structure information added Updated 23 Jan 2017
05 Dec 2016 Trial Update AntibioTx initiates enrolment in a phase I trial for Eczema and Atopic dermatitis in Austria [11] Updated 18 Jan 2017
01 Dec 2016 Phase Change - I/II Phase-I/II clinical trials in Atopic dermatitis in Austria (Topical) (EudraCT2016-003501-33) Updated 08 Dec 2016
01 Dec 2016 Phase Change - I/II Phase-I/II clinical trials in Eczema in Austria (Topical) (EudraCT2016-003501-33) Updated 08 Dec 2016
22 Sep 2016 Regulatory Status AntibioTx files a CTA with the Austrian Agency for Health and Food Safety for a phase I/II trial for Atopic dermatitis and Eczema [12] Updated 16 Dec 2016
25 May 2016 Patent Information European Patent Office recognises primary claims of niclosamide topical gel, as novel and inventive [20] Updated 16 Dec 2016
29 Apr 2016 Regulatory Status Austrian Agency for Health and Food Safety confirms entry of niclosamide topical gel to clinical phase, subject to successful completion of tolerability study [13] Updated 16 Dec 2016
25 Mar 2016 Regulatory Status AntibioTx plans to conduct pre-IND meeting with the US FDA in second half of 2016 Updated 16 Dec 2016
16 Mar 2016 Patent Information Two additional patents filed for for niclosamide topical gel [21] Updated 08 Dec 2016
21 Dec 2015 Phase Change - Preclinical Preclinical trials in Atopic dermatitis in Denmark (Topical) [18] Updated 08 Dec 2016
21 Dec 2015 Phase Change - Preclinical Preclinical trials in Eczema in Denmark (Topical) [18] Updated 08 Dec 2016

References

  1. AntibioTx Announces Company Name Change to UNION therapeutics.

    Media Release
  2. UNION therapeutics launches COVID-19 program in collaboration with Institut Pasteur Korea.

    Media Release
  3. UNION initiates Phase 2b Dose-Ranging Study Evaluating ATx201 OINTMENT in Patients with Mild-to-Moderate Atopic Dermatitis.

    Media Release
  4. A Randomized, Double-Blind, Parallel Group, Vehicle-Controlled Phase 2 Study to Evaluate the Safety and Efficacy of Topical ATx201 OINTMENT in Adolescents and Adults with Mild to Moderate Atopic Dermatitis

    ctiprofile
  5. A Double-Blind, Randomized, Intraindividual, Vehicle-Controlled, Phase 2 Study to Evaluate the Safety and Efficacy of Topically Applied ATx201 in Subjects With Moderate Atopic Dermatitis

    ctiprofile
  6. UNION therapeutics Announces Completion of Phase 2 studies with ATx201.

    Media Release
  7. A Single-Site Study To Evaluate the Sensitization Potential of Topically Applied ATx201 in Healthy Human Volunteers

    ctiprofile
  8. UNION therapeutics Announces Successful Phase 1 Study Completion with ATx201.

    Media Release
  9. A Single-Site Study To Evaluate The Irritation Potential Of Topically Applied ATx201 In Healthy Human Volunteers on Intact and Abraded Skin

    ctiprofile
  10. AntibioTx announces Phase I study results for ATx201.

    Media Release
  11. ATx201 first subject enrolled.

    Media Release
  12. Clinical Trial Application (CTA) submitted to the regulatory authorities to initiate Phase I and Phase II studies on ATx201.

    Media Release
  13. Regulatory Advise meeting with Austrian Authorities confirms green lights to move into the clinic (Phase I / II) upon successful completion of tolerability study in mini-pigs.

    Media Release
  14. A Prospective, Single Center, Randomized, Double-blind, Placebo Controlled Study in Two Phases to Evaluate the Safety and Efficacy of ATx201 as a Topical Antibiotic Agent

    ctiprofile
  15. In vivo study in mini-pigs confirmed systemic safety and no genotoxicity of lead candidate (ATx201).

    Media Release
  16. 28-Day local tolerability study of ATx201 applied daily to Gottingen Mini-pigs initiated. The study is conducted according to GLP.

    Media Release
  17. GLP report following 28-day repeat dosing in Gottingen minipigs conclude that proprietary formulations of ATx201 are well tolerated with good PK data and very low systemic exposure.

    Media Release
  18. Study of AntibioTx's ATx201 Dermal Formulation Initiated at Sinclair Research Center.

    Media Release
  19. Randomized, Double-Blind, Vehicle Controlled, Phase 2 Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Activity of Topical ATx201 GEL (2% and 4%) in Outpatients With Impetigo

    ctiprofile
  20. European Patent Office recognizes primary claims of initial ATx201 patent filing to be novel and inventive.

    Media Release
  21. Two additional patents filed on compound class and ATx201.

    Media Release
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