Phase 1 and 2 Randomized Clinical Studies Determine Lack of Efficacy for Anti-IL-17C Antibody MOR106 in Moderate–Severe Atopic Dermatitis

Diamant Thaçi; Dave Singh; Mark Lee; Helen Timmis; Dominique Jacobs; Paul Passier; Susanne Rohrer; Johan Beetens; De Phung; Eric Sondag; Goran Babic; Guido Würth; Pia Kloepfer; Stefan Härtle; Silke Hüttner

doi:10.3390/jcm11237244

Phase 1 and 2 Randomized Clinical Studies Determine Lack of Efficacy for Anti-IL-17C Antibody MOR106 in Moderate–Severe Atopic Dermatitis

Diamant Thaçi^*, Dave Singh, Mark Lee, Helen Timmis, Dominique Jacobs, Paul Passier, Susanne Rohrer, Johan Beetens, De Phung, Eric Sondag, Goran Babic, Guido Würth, Pia Kloepfer, Stefan Härtle, Silke Hüttner

^*Corresponding author for this work

Institute of Inflammation Medicine

9 Citations (Scopus)

Abstract

Interleukin 17C (IL-17C) modulates epithelial inflammation and has a possible role in atopic dermatitis (AD) pathology. Four randomized clinical studies (Phase 1 and 2) investigated the safety, tolerability, efficacy, and pharmacokinetic profile of the anti-IL-17C monoclonal antibody MOR106 for up to 12 weeks (NCT03568071: n = 207 adults with moderate–severe AD; NCT03689829 Part 1: n = 32 healthy males; NCT03689829 Part 2: n = 44 adults with moderate–severe AD; and NCT03864627: n = 76 adults with moderate–severe AD). In these studies, MOR106 was either administered intravenously (i.v.) every 2 or 4 weeks at doses between 1–10 mg/kg, or subcutaneously (s.c.), either as a single dose or doses every 2 weeks at 320 mg. Overall, MOR106 was well-tolerated, and the safety profile was consistent with monoclonal antibodies approved for AD. Bioavailability following s.c. dosing was 55%, and steady-state drug levels were reached at 2–4 weeks. Ongoing studies were terminated following a futility analysis of the Phase 2 placebo-controlled dose-finding study (NCT03568071) due to a low probability for achieving the primary efficacy endpoint. Cumulatively, MOR106 demonstrated ineffectiveness for the treatment of AD, but its safety and pharmacokinetic characteristics warrant further drug development in other indications. Funding: sponsored by Galapagos NV; funded by Novartis AG.

Original language	English
Article number	7244
Journal	Journal of Clinical Medicine
Volume	11
Issue number	23
ISSN	2077-0383
DOIs	https://doi.org/10.3390/jcm11237244
Publication status	Published - 12.2022

Funding

D.T.: Advisory council or committee: AbbVie, Almirall, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, Target-Solution and UCB; Honoraria: AbbVie, Almirall, Amgen, Biogen Idec, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Leo Pharma, Novartis, Pfizer, Roche-Posay, Sanofi and UCB; Consultancy fee: AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, Target-Solution, and UCB; Grants or funds: Novartis and Leo Pharma. D.S.: Consulting fee: Aerogen, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, CSL Behring, Epiendo, Genentech, GlaxoSmithKline, Glenmark, Gossamerbio, Kinaset, Menarini, Novartis, Pulmatrix, Sanofi, Synairgen, Teva, Theravance and Verona. M.L.: Grants or funds: received research funding from Abbvie, Lilly, Novartis, Arcutis, Incyte, Rapt, Almirall, Brickell, Concert, Reistone, Leo Pharma, UCB, Aclaris, and Janssen. H.T.: Employment: Galapagos NV until January 2022; Ownership of stock/shares: Galapagos warrants. D.J.: Employment: Galapagos NV; Ownership of stock/shares: Galapagos warrants. S.H. (Stefan Härtle): Employment: MorphoSys AG; Ownership of stock/shares: MorphoSys AG. P.K.: Employment: MorphoSys AG. P.P.: Employment: Galapagos NV. S.R.: Employment: Novartis; Ownership of stock/shares: Novartis. J.B.: Employment: Galapagos (2008–2019); Ownership of stock/shares: Galapagos. D.P.: Employment: previous employment at Galapagos. E.S.: Employment: previous employment at Galapagos; Ownership of stock/shares: Galapagos warrants. G.B.: Employment: previous employment at MorphoSys AG. G.W.: Employment: employed by MorphoSys AG until 14 July 2021. Ownership of stock/shares: MorphoSys and Galapagos. S.H. (Silke Hüttner: Employment: previous employment at Galapagos NV until end of October 2021; Ownership of stock/shares: Galapagos warrants. The studies were sponsored by Galapagos NV, Mechelen, Belgium and Novartis Pharma AG, Basel, Switzerland. We are grateful to, and wish thank, all patients, investigators, study sites, research teams, and other collaborators who participated in these studies; with special thanks to the Galapagos clinical study teams for their contributions. We thank Diamant Thaçi for his work as the coordinating chief investigator in study 1 and all of the coordinating investigators in countries where study participants were enrolled, the members of the Independent Safety Monitoring Committee and the members of the Scientific Advisory Board. We thank Karine Muller from Galapagos for her assistance with the statistical analysis, and Yasser Khder from Novartis for his input into the study designs and the interpretation of results. Due to the large number of people involved in the planning and conduct of the studies, we are unfortunately unable to acknowledge every individual by name. Dave Singh is supported by the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre (BRC). Medical writing support for the development of this manuscript, under the direction of the authors, was provided by James Currie of Ashfield MedComms, an Inizio Company and funded by Novartis Pharma AG, Basel, Switzerland.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Areas and Centers

Academic Focus: Center for Infection and Inflammation Research (ZIEL)
Centers: Center for Research on Inflammation of the Skin (CRIS)

DFG Research Classification Scheme

2.22-19 Dermatology

Access to Document

10.3390/jcm11237244

Cite this

Thaçi, D., Singh, D., Lee, M., Timmis, H., Jacobs, D., Passier, P., Rohrer, S., Beetens, J., Phung, D., Sondag, E., Babic, G., Würth, G., Kloepfer, P., Härtle, S., & Hüttner, S. (2022). Phase 1 and 2 Randomized Clinical Studies Determine Lack of Efficacy for Anti-IL-17C Antibody MOR106 in Moderate–Severe Atopic Dermatitis. Journal of Clinical Medicine, 11(23), Article 7244. https://doi.org/10.3390/jcm11237244

@article{3304e7efd2ee4e639a7e41d7d7d17d74,

title = "Phase 1 and 2 Randomized Clinical Studies Determine Lack of Efficacy for Anti-IL-17C Antibody MOR106 in Moderate–Severe Atopic Dermatitis",

abstract = "Interleukin 17C (IL-17C) modulates epithelial inflammation and has a possible role in atopic dermatitis (AD) pathology. Four randomized clinical studies (Phase 1 and 2) investigated the safety, tolerability, efficacy, and pharmacokinetic profile of the anti-IL-17C monoclonal antibody MOR106 for up to 12 weeks (NCT03568071: n = 207 adults with moderate–severe AD; NCT03689829 Part 1: n = 32 healthy males; NCT03689829 Part 2: n = 44 adults with moderate–severe AD; and NCT03864627: n = 76 adults with moderate–severe AD). In these studies, MOR106 was either administered intravenously (i.v.) every 2 or 4 weeks at doses between 1–10 mg/kg, or subcutaneously (s.c.), either as a single dose or doses every 2 weeks at 320 mg. Overall, MOR106 was well-tolerated, and the safety profile was consistent with monoclonal antibodies approved for AD. Bioavailability following s.c. dosing was 55\%, and steady-state drug levels were reached at 2–4 weeks. Ongoing studies were terminated following a futility analysis of the Phase 2 placebo-controlled dose-finding study (NCT03568071) due to a low probability for achieving the primary efficacy endpoint. Cumulatively, MOR106 demonstrated ineffectiveness for the treatment of AD, but its safety and pharmacokinetic characteristics warrant further drug development in other indications. Funding: sponsored by Galapagos NV; funded by Novartis AG.",

author = "Diamant Tha{\c c}i and Dave Singh and Mark Lee and Helen Timmis and Dominique Jacobs and Paul Passier and Susanne Rohrer and Johan Beetens and De Phung and Eric Sondag and Goran Babic and Guido W{\"u}rth and Pia Kloepfer and Stefan H{\"a}rtle and Silke H{\"u}ttner",

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Thaçi, D, Singh, D, Lee, M, Timmis, H, Jacobs, D, Passier, P, Rohrer, S, Beetens, J, Phung, D, Sondag, E, Babic, G, Würth, G, Kloepfer, P, Härtle, S & Hüttner, S 2022, 'Phase 1 and 2 Randomized Clinical Studies Determine Lack of Efficacy for Anti-IL-17C Antibody MOR106 in Moderate–Severe Atopic Dermatitis', Journal of Clinical Medicine, vol. 11, no. 23, 7244. https://doi.org/10.3390/jcm11237244

TY - JOUR

T1 - Phase 1 and 2 Randomized Clinical Studies Determine Lack of Efficacy for Anti-IL-17C Antibody MOR106 in Moderate–Severe Atopic Dermatitis

AU - Thaçi, Diamant

AU - Singh, Dave

AU - Lee, Mark

AU - Timmis, Helen

AU - Jacobs, Dominique

AU - Passier, Paul

AU - Rohrer, Susanne

AU - Beetens, Johan

AU - Phung, De

AU - Sondag, Eric

AU - Babic, Goran

AU - Würth, Guido

AU - Kloepfer, Pia

AU - Härtle, Stefan

AU - Hüttner, Silke

PY - 2022/12

Y1 - 2022/12

N2 - Interleukin 17C (IL-17C) modulates epithelial inflammation and has a possible role in atopic dermatitis (AD) pathology. Four randomized clinical studies (Phase 1 and 2) investigated the safety, tolerability, efficacy, and pharmacokinetic profile of the anti-IL-17C monoclonal antibody MOR106 for up to 12 weeks (NCT03568071: n = 207 adults with moderate–severe AD; NCT03689829 Part 1: n = 32 healthy males; NCT03689829 Part 2: n = 44 adults with moderate–severe AD; and NCT03864627: n = 76 adults with moderate–severe AD). In these studies, MOR106 was either administered intravenously (i.v.) every 2 or 4 weeks at doses between 1–10 mg/kg, or subcutaneously (s.c.), either as a single dose or doses every 2 weeks at 320 mg. Overall, MOR106 was well-tolerated, and the safety profile was consistent with monoclonal antibodies approved for AD. Bioavailability following s.c. dosing was 55%, and steady-state drug levels were reached at 2–4 weeks. Ongoing studies were terminated following a futility analysis of the Phase 2 placebo-controlled dose-finding study (NCT03568071) due to a low probability for achieving the primary efficacy endpoint. Cumulatively, MOR106 demonstrated ineffectiveness for the treatment of AD, but its safety and pharmacokinetic characteristics warrant further drug development in other indications. Funding: sponsored by Galapagos NV; funded by Novartis AG.

AB - Interleukin 17C (IL-17C) modulates epithelial inflammation and has a possible role in atopic dermatitis (AD) pathology. Four randomized clinical studies (Phase 1 and 2) investigated the safety, tolerability, efficacy, and pharmacokinetic profile of the anti-IL-17C monoclonal antibody MOR106 for up to 12 weeks (NCT03568071: n = 207 adults with moderate–severe AD; NCT03689829 Part 1: n = 32 healthy males; NCT03689829 Part 2: n = 44 adults with moderate–severe AD; and NCT03864627: n = 76 adults with moderate–severe AD). In these studies, MOR106 was either administered intravenously (i.v.) every 2 or 4 weeks at doses between 1–10 mg/kg, or subcutaneously (s.c.), either as a single dose or doses every 2 weeks at 320 mg. Overall, MOR106 was well-tolerated, and the safety profile was consistent with monoclonal antibodies approved for AD. Bioavailability following s.c. dosing was 55%, and steady-state drug levels were reached at 2–4 weeks. Ongoing studies were terminated following a futility analysis of the Phase 2 placebo-controlled dose-finding study (NCT03568071) due to a low probability for achieving the primary efficacy endpoint. Cumulatively, MOR106 demonstrated ineffectiveness for the treatment of AD, but its safety and pharmacokinetic characteristics warrant further drug development in other indications. Funding: sponsored by Galapagos NV; funded by Novartis AG.

UR - https://www.scopus.com/pages/publications/85143606580

U2 - 10.3390/jcm11237244

DO - 10.3390/jcm11237244

M3 - Journal articles

AN - SCOPUS:85143606580

SN - 2077-0383

VL - 11

JO - Journal of Clinical Medicine

JF - Journal of Clinical Medicine

IS - 23

M1 - 7244

ER -

Phase 1 and 2 Randomized Clinical Studies Determine Lack of Efficacy for Anti-IL-17C Antibody MOR106 in Moderate–Severe Atopic Dermatitis

Abstract

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DFG Research Classification Scheme

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