Long-term efficacy and safety of netakimab in patients with moderate-to-severe psoriasis. Results of phase II open-label extension clinical study BCD-085-2-ext

Cover Page


Cite item

Full Text

Abstract

Netakimabis original monoclonal antibody against IL-17. This article outlines the key results of a phase II open-label extension trial of netakimab 80 mg and 120 mg in patients with moderate-to-severe psoriasis.

The main aim of the trial is to estimate efficacy, safety and immunogenicity of long-term treatment with netakimab 80 mg and 120 mg in patients with moderate-to-severe psoriasis.

Materials and methods. The BCD-085-2-ext study is a comparative, open-label phase 2 clinical study of the effi - cacy and safety of netakimab in patients with moderate-to-severe plaque psoriasis who had finished BCD-085-2 (NCT02762994) trial. Main efficacy endpoints includePASI75, PASI90, PASI100, sPGA = 0–1 on week 38 of the trial, long-term PASI75/90/100 retention, efficacy keeping after switch from once every 2 week regimen to once every 4 week regimen. Safety endpoints include adverse events, serious adverse events number and their profile.

Results. 103 patients were included. PASI75 at week 38 was reached by 98.06 %, PASI90 — by 92.23 %, PASI100 — by 59.22 % of patients. There were no cases of serious adverse event, early with drawal due to adverse events and cases of grade 4 toxicity according to CTCAE 4.03. There were no cases of binding antibodies to netakimab during the 38 weeks of the study.

Conclusion. The first Russian original IL-17 inhibitor netakimabis promising modern medicine for moderate-to-severe plaque psoriasis treatment. Netakimabshowed high efficacy, favorable safety profile and low immunogenicity during one year of the treatment.

About the authors

A. L. Bakulev

Saratov State Medical Universit y named after V. I. Razumovsky, Ministr y of Health of the Russian Federation

Email: fake@neicon.ru
Andrey L. Bakulev — Dr. Sci. (Med.), Prof., Head of the Department of Dermatology and Cosmetology Россия

A. V. Samtsov

S. M. Kirov Militar y Medical Academy, Ministr y of Defence of the Russian Federation

Email: fake@neicon.ru
Alexey V. Samtsov — Dr. Sci. (Med.), Prof., Head of the Department of Skin and Venereal Diseases Россия

A. A. Kubanov

State Research Center of Dermatovenereology and Cosmetology, Ministr y of Health of the Russian Federation

Email: fake@neicon.ru
Alexey A. Kubanov — Dr. Sci. (Med.), Prof., RAS Corresponding Member, Acting Director Россия

V. R. Khairutdinov

S. M. Kirov Militar y Medical Academy, Ministr y of Defence of the Russian Federation

Email: fake@neicon.ru
Vladislav R. Khairutdinov — Dr. Sci. (Med.), Assoc. Prof. of the Department of Skin and Venereal Diseases Россия

M. M. Kokhan

Ural Research Institute for Dermatovenerology and Immunopatology

Email: fake@neicon.ru
Muza M. Kokhan — Dr. Sci. (Med.), Prof., Head of the Scientific Clinical Department of Dermatology Россия

A. V. Artemyeva

BIOCAD

Email: fake@neicon.ru
Antonina V. Artemyeva — Medical Expert Россия

S. I. Derbin

BIOCAD

Author for correspondence.
Email: derbin@biocad.ru

Sergey I. Derbin* — Senior Medical Advisor

tel. +7 (905) 274-65-59

Россия

E. V. Chernyaeva

BIOCAD

Email: fake@neicon.ru
Ekaterina V. Chernyaeva — Director for R&D in the Field of Rheumatology and Dermatology Россия

R. A. Ivanov

BIOCAD

Email: fake@neicon.ru
Roman A. Ivanov — Cand. Sci. (Med.), Deputy General Director for Biomedical R&D Россия

References

  1. Кубанова А. А., Кубанов А. А., Знаменская Л. Ф., Чикин В.В., Бакулев А. Л., Хобейш М. М. и др. Псориаз. В кн.: Федеральные клинические рекомендации. Дерматовенерология, 2015: Болезни кожи. Инфекции, передаваемые половым путем. 5-е изд., перераб. и доп. М.: Деловой экспресс, 2016. С. 415–470. [Kubanova A. A., Kubanov A. A., Znamenskaya L. F., Chikin V. V., Bakulev A. L., Khobeysh M. M. et al. Psoriasis. In: Federal clinical guidelines. Dermatovenerology, 2015: Diseases of the skin. Sexually transmitted infections. 5th ed., revised and enlarged. Moscow: Delovoy ekspress, 2016. P. 415–470. (In Russ.)]
  2. Бакулев А. Л. Эволюция представлений о псориазе и терапевтических подходах по ведению пациентов. BCD-085 — первый отечественный генно-инженерный биологический препарат для лечения больных псориазом. Вестник дерматологии и венерологии. 2018;94(5):26–32. [Bakulev A. L. Evolution of the understanding of psoriasis and therapeutic approaches used to managesuch patients. BCD-085 is the first Russian genetically- engineered biological preparation for the treatment of patients suffering from psoriasis. Vestnik Dermatologii i Venerologii. 2018;94(5):26–32. (In Russ.)]. doi: 10.25208/0042-4609-2018-94-5-26-32
  3. Bovenschen H. J., Van de Kerkhof P. C., Van Erp P. E. et al. Foxp3+ Regulatory T Cells of Psoriasis Patients Easily Differentiate into IL-17A-Producing Cells and Are Found in Lesional Skin. Journal of Investigative Dermatology. 2011;131:1853–1860.
  4. Cua Daniel J., Tato Cristina M. Innate IL-17-producing cells: the sentinels of the immune system. Nature Reviews Immunology. 2010/06/18/online. doi: 10.1038/nri2800
  5. Korn T., Bettelli E., Oukka M., Kuchroo V. K. IL-17 and Th17 Cells. Annu Rev Immunol. 2009;27:485–517.
  6. Hawkes J. E., Chan T. C., Krueger J. G. Psoriasis pathogenesis and the development of novel targeted immune therapies. J Allergy Clin Immunol. 2017;140(3):645–653.
  7. Langley R. G., Elewski B. E., Lebwohl M. et al. Secukinumab in Plaque Psoriasis — Results of Two Phase 3 Trials. N Engl J Med. 2014;371:326–338.
  8. Gordon K. B., Blauvelt A., Papp K. A., Langley R. G. et al. UNCOVER- 1 Study Group; UNCOVER-2 Study Group; UNCOVER-3 Study Group. Phase 3 Trials of Ixekizumab in Moderate-to-Severe Plaque Psoriasis. N Engl J Med. 2016 Jul 28;375(4):345–356.
  9. Самцов А. В., Хайрутдинов В. Р., Бакулев А. Л., Кубанов А. А., Карамова А. Э. и др. Эффективность и безопасность препарата BCD- 085 — оригинального моноклонального антитела против интерлейкина-17 у пациентов со среднетяжелым и тяжелым вульгарным псориазом. Результаты II фазы международного многоцентрового сравнительного рандомизированного двойного слепого плацебо-контролируемого клинического исследования. Вестник дерматологии и венерологии. 2017;5:52–63. [Samtsov A. V., Khairutdinov V. R., Bakulev A. L., Kubanov A. A., Karamova A. E. et al. Efficacy and safety of BCD-085, a novel IL-17 inhibitor. Results of phase II clinical trial in patients with moderate-to-severe plaquepsoriasis. Vestnik Dermatologii i Venerologii. 2017;5:52–63. (In Russ.)]
  10. Coates L., Murphy R., Helliwell P. New GRAPPA recommendations for the management of psoriasis and psoriatic arthritis: process, challenges and implementation. Br J Dermatol. 2016;174:1174–1178. doi: 10.1111/bjd.14667
  11. Gisondi P. et al. Italian guidelines on the systemic treatments of moderate-to-severe plaque psoriasis. J Eur Acad Dermatol Venereol. 2017;31:774–790. doi: 10.1111/jdv.14114
  12. Nast A. et al. S3 Guideline for the treatment of psoriasis vulgaris, update — Short version part 1 — Systemic treatment. JDDG: Journal der Deutschen Dermatologischen Gesellschaft. 2018;16:645–669. doi: 10.1111/ddg.13516
  13. Насонов Е. Л., Мазуров В. И., Усачева Ю. В. и др. Разработки отечественных оригинальных генно-нженерных биологических препаратов для лечения иммуновоспалительных ревматических заболеваний. Научно-практическая ревматология. 2017;55(2):201–210. [Nasonov E. L., Mazurov V. I., Usacheva Yu. V. et al. Developments of Russian original biological agents for the treatment of immunoinflammatory rheumatic diseases. Rheumatology Science and Practice. 2017;55(2):201–210. (In Russ.)]. doi: 10.14412/1995-4484-2017-201-210
  14. Chernyaeva E., Eremeeva A., Galustyan A. et al. Pharmacokinetics, Safety and Tolerance of BCD-085, a Novel IL-17 Inhibitor, Based on the Results of Phase 1 Clinical Study in Healthy Volunteers. Ann Rheum Dis. 2016; 75(Suppl 2):429.1–429. doi: 10.1136/annrheumdis-2016-eular.1615
  15. Shear N., Hartmann M. et al. Long-term efficacy and safety of infliximab maintenance therapy in patients with plaque-type psoriasis in real-world practice. Br J Dermatol. 2014;171:631–641. doi: 10.1111/bjd.13004
  16. Reich K., Nestle F. O., Papp K. et al. Infliximab induction and maintenance therapy for moderate-to-severe psoriasis: a phase III, multicentre, double-blindtrial. Lancet. 2005;366(9494):1367–1374. doi: 10.1016/S0140-6736(05)67566-6
  17. Strober B. E., Clay Cather J., Cohen D., Crowley J. J., Gordon K. B., Gottlieb A. B. et al. A Delphi Consensus Approach to Challenging Case Scenarios in Moderate-to-Severe Psoriasis: Part 1. Dermatol Ther (Heidelb). 2012 Dec; 2(1):1. Epub 2012 Mar 17
  18. Strober B. E., Clay Cather J., Cohen D., Crowley J. J., Gordon K. B., Gottlieb A. B. et al. A Delphi Consensus Approach to Challenging Case Scenarios in Moderate-to-Severe Psoriasis: Part. 2. Dermatol Ther (Heidelb). 2012 Dec; 2(1):2. Epub 2012 Mar 30

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2019 Bakulev A.L., Samtsov A.V., Kubanov A.A., Khairutdinov V.R., Kokhan M.M., Artemyeva A.V., Derbin S.I., Chernyaeva E.V., Ivanov R.A.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 60448 от 30.12.2014.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies