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
  • Authors: Bakulev A.L.1, Samtsov A.V.2, Kubanov A.A.3, Khairutdinov V.R.2, Kokhan M.M.4, Artemyeva A.V.5, Derbin S.I.5, Chernyaeva E.V.5, Ivanov R.A.5
  • Affiliations:
    1. Saratov State Medical Universit y named after V. I. Razumovsky, Ministr y of Health of the Russian Federation
    2. S. M. Kirov Militar y Medical Academy, Ministr y of Defence of the Russian Federation
    3. State Research Center of Dermatovenereology and Cosmetology, Ministr y of Health of the Russian Federation
    4. Ural Research Institute for Dermatovenerology and Immunopatology
    5. BIOCAD
  • Issue: Vol 95, No 3 (2019)
  • Pages: 54-64
  • Section: DRUG TREATMENT IN DERMATOVENEROLOGY
  • URL: http://www.vestnikdv.ru/jour/article/view/499
  • DOI: https://doi.org/10.25208/0042-4609-2019-95-3-54-64

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

Russian Federation Andrey L. Bakulev — Dr. Sci. (Med.), Prof., Head of the Department of Dermatology and Cosmetology

A. V. Samtsov

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

Email: fake@neicon.ru

Russian Federation Alexey V. Samtsov — Dr. Sci. (Med.), Prof., Head of the Department of Skin and Venereal Diseases

A. A. Kubanov

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

Email: fake@neicon.ru

Russian Federation Alexey A. Kubanov — Dr. Sci. (Med.), Prof., RAS Corresponding Member, Acting Director

V. R. Khairutdinov

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

Email: fake@neicon.ru

Russian Federation Vladislav R. Khairutdinov — Dr. Sci. (Med.), Assoc. Prof. of the Department of Skin and Venereal Diseases

M. M. Kokhan

Ural Research Institute for Dermatovenerology and Immunopatology

Email: fake@neicon.ru

Russian Federation Muza M. Kokhan — Dr. Sci. (Med.), Prof., Head of the Scientific Clinical Department of Dermatology

A. V. Artemyeva

BIOCAD

Email: fake@neicon.ru

Russian Federation Antonina V. Artemyeva — Medical Expert

S. I. Derbin

BIOCAD

Author for correspondence.
Email: derbin@biocad.ru

Russian Federation

Sergey I. Derbin* — Senior Medical Advisor

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

E. V. Chernyaeva

BIOCAD

Email: fake@neicon.ru

Russian Federation Ekaterina V. Chernyaeva — Director for R&D in the Field of Rheumatology and Dermatology

R. A. Ivanov

BIOCAD

Email: fake@neicon.ru

Russian Federation Roman A. Ivanov — Cand. Sci. (Med.), Deputy General Director for Biomedical R&D

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

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