Topical niclosamide (ATx201) reduces Staphylococcus aureus colonization and increases Shannon diversity of the skin microbiome in atopic dermatitis patients in a randomized, double-blind, placebo-controlled Phase 2 trial

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Topical niclosamide (ATx201) reduces Staphylococcus aureus colonization and increases Shannon diversity of the skin microbiome in atopic dermatitis patients in a randomized, double-blind, placebo-controlled Phase 2 trial. / Weiss, Anne; Delavenne, Emilie; Matias, Carina; Lagler, Heimo; Simon, Daniel; Li, Ping; Hansen, Jon U; Dos Santos, Teresa Pires; Jana, Bimal; Priemel, Petra; Bangert, Christine; Bauer, Martin; Eberl, Sabine; Nussbaumer-Pröll, Alina; Anne Österreicher, Zoe; Matzneller, Peter; Quint, Tamara; Weber, Maria; Nielsen, Hanne Mørck; Rades, Thomas; Johansen, Helle Krogh; Westh, Henrik; Kim, Wooseong; Mylonakis, Eleftherios; Friis, Christian; Guardabassi, Luca; Pace, John; Lundberg, Carina Vingsbo; M'Zali, Fatima; Butty, Pascal; Sørensen, Nikolaj; Nielsen, Henrik Bjørn; Toft-Kehler, Rasmus; Guttman-Yassky, Emma; Stingl, Georg; Zeitlinger, Markus; Sommer, Morten.

In: Clinical and Translational Medicine, Vol. 12, No. 5, e790, 2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Weiss, A, Delavenne, E, Matias, C, Lagler, H, Simon, D, Li, P, Hansen, JU, Dos Santos, TP, Jana, B, Priemel, P, Bangert, C, Bauer, M, Eberl, S, Nussbaumer-Pröll, A, Anne Österreicher, Z, Matzneller, P, Quint, T, Weber, M, Nielsen, HM, Rades, T, Johansen, HK, Westh, H, Kim, W, Mylonakis, E, Friis, C, Guardabassi, L, Pace, J, Lundberg, CV, M'Zali, F, Butty, P, Sørensen, N, Nielsen, HB, Toft-Kehler, R, Guttman-Yassky, E, Stingl, G, Zeitlinger, M & Sommer, M 2022, 'Topical niclosamide (ATx201) reduces Staphylococcus aureus colonization and increases Shannon diversity of the skin microbiome in atopic dermatitis patients in a randomized, double-blind, placebo-controlled Phase 2 trial', Clinical and Translational Medicine, vol. 12, no. 5, e790. https://doi.org/10.1002/ctm2.790

APA

Weiss, A., Delavenne, E., Matias, C., Lagler, H., Simon, D., Li, P., Hansen, J. U., Dos Santos, T. P., Jana, B., Priemel, P., Bangert, C., Bauer, M., Eberl, S., Nussbaumer-Pröll, A., Anne Österreicher, Z., Matzneller, P., Quint, T., Weber, M., Nielsen, H. M., ... Sommer, M. (2022). Topical niclosamide (ATx201) reduces Staphylococcus aureus colonization and increases Shannon diversity of the skin microbiome in atopic dermatitis patients in a randomized, double-blind, placebo-controlled Phase 2 trial. Clinical and Translational Medicine, 12(5), [e790]. https://doi.org/10.1002/ctm2.790

Vancouver

Weiss A, Delavenne E, Matias C, Lagler H, Simon D, Li P et al. Topical niclosamide (ATx201) reduces Staphylococcus aureus colonization and increases Shannon diversity of the skin microbiome in atopic dermatitis patients in a randomized, double-blind, placebo-controlled Phase 2 trial. Clinical and Translational Medicine. 2022;12(5). e790. https://doi.org/10.1002/ctm2.790

Author

Weiss, Anne ; Delavenne, Emilie ; Matias, Carina ; Lagler, Heimo ; Simon, Daniel ; Li, Ping ; Hansen, Jon U ; Dos Santos, Teresa Pires ; Jana, Bimal ; Priemel, Petra ; Bangert, Christine ; Bauer, Martin ; Eberl, Sabine ; Nussbaumer-Pröll, Alina ; Anne Österreicher, Zoe ; Matzneller, Peter ; Quint, Tamara ; Weber, Maria ; Nielsen, Hanne Mørck ; Rades, Thomas ; Johansen, Helle Krogh ; Westh, Henrik ; Kim, Wooseong ; Mylonakis, Eleftherios ; Friis, Christian ; Guardabassi, Luca ; Pace, John ; Lundberg, Carina Vingsbo ; M'Zali, Fatima ; Butty, Pascal ; Sørensen, Nikolaj ; Nielsen, Henrik Bjørn ; Toft-Kehler, Rasmus ; Guttman-Yassky, Emma ; Stingl, Georg ; Zeitlinger, Markus ; Sommer, Morten. / Topical niclosamide (ATx201) reduces Staphylococcus aureus colonization and increases Shannon diversity of the skin microbiome in atopic dermatitis patients in a randomized, double-blind, placebo-controlled Phase 2 trial. In: Clinical and Translational Medicine. 2022 ; Vol. 12, No. 5.

Bibtex

@article{afa75a4329364cd1a8ed899282e9fedc,

title = "Topical niclosamide (ATx201) reduces Staphylococcus aureus colonization and increases Shannon diversity of the skin microbiome in atopic dermatitis patients in a randomized, double-blind, placebo-controlled Phase 2 trial",

abstract = "BACKGROUND: In patients with atopic dermatitis (AD), Staphylococcus aureus frequently colonizes lesions and is hypothesized to be linked to disease severity and progression. Treatments that reduce S. aureus colonization without significantly affecting the skin commensal microbiota are needed.METHODS AND FINDINGS: In this study, we tested ATx201 (niclosamide), a small molecule, on its efficacy to reduce S. aureus and propensity to evolve resistance in vitro. Various cutaneous formulations were then tested in a superficial skin infection model. Finally, a Phase 2 randomized, double-blind and placebo-controlled trial was performed to investigate the impact of ATx201 OINTMENT 2% on S. aureus colonization and skin microbiome composition in patients with mild-to-severe AD (EudraCT:2016-003501-33). ATx201 has a narrow minimal inhibitory concentration distribution (.125-.5 μg/ml) consistent with its mode of action - targeting the proton motive force effectively stopping cell growth. In murine models, ATx201 can effectively treat superficial skin infections of methicillin-resistant S. aureus. In a Phase 2 trial in patients with mild-to-severe AD (N = 36), twice-daily treatment with ATx201 OINTMENT 2% effectively reduces S. aureus colonization in quantitative colony forming unit (CFU) analysis (primary endpoint: 94.4% active vs. 38.9% vehicle success rate, p = .0016) and increases the Shannon diversity of the skin microbiome at day 7 significantly compared to vehicle.CONCLUSION: These results suggest that ATx201 could become a new treatment modality as a decolonizing agent.",

keywords = "Animals, Anti-Bacterial Agents/pharmacology, Dermatitis, Atopic/drug therapy, Humans, Methicillin-Resistant Staphylococcus aureus, Mice, Microbiota, Niclosamide/pharmacology, Ointments/pharmacology, Staphylococcal Infections/drug therapy, Staphylococcus aureus",

author = "Anne Weiss and Emilie Delavenne and Carina Matias and Heimo Lagler and Daniel Simon and Ping Li and Hansen, {Jon U} and {Dos Santos}, {Teresa Pires} and Bimal Jana and Petra Priemel and Christine Bangert and Martin Bauer and Sabine Eberl and Alina Nussbaumer-Pr{\"o}ll and {Anne {\"O}sterreicher}, Zoe and Peter Matzneller and Tamara Quint and Maria Weber and Nielsen, {Hanne M{\o}rck} and Thomas Rades and Johansen, {Helle Krogh} and Henrik Westh and Wooseong Kim and Eleftherios Mylonakis and Christian Friis and Luca Guardabassi and John Pace and Lundberg, {Carina Vingsbo} and Fatima M'Zali and Pascal Butty and Nikolaj S{\o}rensen and Nielsen, {Henrik Bj{\o}rn} and Rasmus Toft-Kehler and Emma Guttman-Yassky and Georg Stingl and Markus Zeitlinger and Morten Sommer",

note = "{\textcopyright} 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.",

year = "2022",

doi = "10.1002/ctm2.790",

language = "English",

volume = "12",

journal = "Clinical and Translational Medicine",

issn = "2001-1326",

publisher = "SpringerOpen",

number = "5",

}

RIS

TY - JOUR

T1 - Topical niclosamide (ATx201) reduces Staphylococcus aureus colonization and increases Shannon diversity of the skin microbiome in atopic dermatitis patients in a randomized, double-blind, placebo-controlled Phase 2 trial

AU - Weiss, Anne

AU - Delavenne, Emilie

AU - Matias, Carina

AU - Lagler, Heimo

AU - Simon, Daniel

AU - Li, Ping

AU - Hansen, Jon U

AU - Dos Santos, Teresa Pires

AU - Jana, Bimal

AU - Priemel, Petra

AU - Bangert, Christine

AU - Bauer, Martin

AU - Eberl, Sabine

AU - Nussbaumer-Pröll, Alina

AU - Anne Österreicher, Zoe

AU - Matzneller, Peter

AU - Quint, Tamara

AU - Weber, Maria

AU - Nielsen, Hanne Mørck

AU - Rades, Thomas

AU - Johansen, Helle Krogh

AU - Westh, Henrik

AU - Kim, Wooseong

AU - Mylonakis, Eleftherios

AU - Friis, Christian

AU - Guardabassi, Luca

AU - Pace, John

AU - Lundberg, Carina Vingsbo

AU - M'Zali, Fatima

AU - Butty, Pascal

AU - Sørensen, Nikolaj

AU - Nielsen, Henrik Bjørn

AU - Toft-Kehler, Rasmus

AU - Guttman-Yassky, Emma

AU - Stingl, Georg

AU - Zeitlinger, Markus

AU - Sommer, Morten

PY - 2022

Y1 - 2022

N2 - BACKGROUND: In patients with atopic dermatitis (AD), Staphylococcus aureus frequently colonizes lesions and is hypothesized to be linked to disease severity and progression. Treatments that reduce S. aureus colonization without significantly affecting the skin commensal microbiota are needed.METHODS AND FINDINGS: In this study, we tested ATx201 (niclosamide), a small molecule, on its efficacy to reduce S. aureus and propensity to evolve resistance in vitro. Various cutaneous formulations were then tested in a superficial skin infection model. Finally, a Phase 2 randomized, double-blind and placebo-controlled trial was performed to investigate the impact of ATx201 OINTMENT 2% on S. aureus colonization and skin microbiome composition in patients with mild-to-severe AD (EudraCT:2016-003501-33). ATx201 has a narrow minimal inhibitory concentration distribution (.125-.5 μg/ml) consistent with its mode of action - targeting the proton motive force effectively stopping cell growth. In murine models, ATx201 can effectively treat superficial skin infections of methicillin-resistant S. aureus. In a Phase 2 trial in patients with mild-to-severe AD (N = 36), twice-daily treatment with ATx201 OINTMENT 2% effectively reduces S. aureus colonization in quantitative colony forming unit (CFU) analysis (primary endpoint: 94.4% active vs. 38.9% vehicle success rate, p = .0016) and increases the Shannon diversity of the skin microbiome at day 7 significantly compared to vehicle.CONCLUSION: These results suggest that ATx201 could become a new treatment modality as a decolonizing agent.

AB - BACKGROUND: In patients with atopic dermatitis (AD), Staphylococcus aureus frequently colonizes lesions and is hypothesized to be linked to disease severity and progression. Treatments that reduce S. aureus colonization without significantly affecting the skin commensal microbiota are needed.METHODS AND FINDINGS: In this study, we tested ATx201 (niclosamide), a small molecule, on its efficacy to reduce S. aureus and propensity to evolve resistance in vitro. Various cutaneous formulations were then tested in a superficial skin infection model. Finally, a Phase 2 randomized, double-blind and placebo-controlled trial was performed to investigate the impact of ATx201 OINTMENT 2% on S. aureus colonization and skin microbiome composition in patients with mild-to-severe AD (EudraCT:2016-003501-33). ATx201 has a narrow minimal inhibitory concentration distribution (.125-.5 μg/ml) consistent with its mode of action - targeting the proton motive force effectively stopping cell growth. In murine models, ATx201 can effectively treat superficial skin infections of methicillin-resistant S. aureus. In a Phase 2 trial in patients with mild-to-severe AD (N = 36), twice-daily treatment with ATx201 OINTMENT 2% effectively reduces S. aureus colonization in quantitative colony forming unit (CFU) analysis (primary endpoint: 94.4% active vs. 38.9% vehicle success rate, p = .0016) and increases the Shannon diversity of the skin microbiome at day 7 significantly compared to vehicle.CONCLUSION: These results suggest that ATx201 could become a new treatment modality as a decolonizing agent.

KW - Animals

KW - Anti-Bacterial Agents/pharmacology

KW - Dermatitis, Atopic/drug therapy

KW - Humans

KW - Methicillin-Resistant Staphylococcus aureus

KW - Mice

KW - Microbiota

KW - Niclosamide/pharmacology

KW - Ointments/pharmacology

KW - Staphylococcal Infections/drug therapy

KW - Staphylococcus aureus

U2 - 10.1002/ctm2.790

DO - 10.1002/ctm2.790

M3 - Journal article

C2 - 35522900

VL - 12

JO - Clinical and Translational Medicine

JF - Clinical and Translational Medicine

SN - 2001-1326

IS - 5

M1 - e790

ER -

ID: 322672163