A Two-Stage Study of the Efficacy, Safety, Pharmacokinetics, Pharmacodynamics and Immunogenicity of Various Doses of Levilimab When Administered Intravenously and Subcutaneously to Healthy Subjects and Subjects With Active Rheumatoid Arthritis

This is a two-stage study of efficacy, safety, pharmacokinetics, pharmacodynamics, and immunogenicity of various doses of levilimab when administered intravenously and subcutaneously to healthy subjects and subjects with active rheumatoid arthritis resistant to methotrexate monotherapy.
Aim of the Stage 1 is to study the tolerability, safety, immunogenicity, and main pharmacokinetic and pharmacodynamic parameters of levilimab after its single subcutaneous or intravenous administration at ascending doses to healthy subjects.
Aim of the Stage 2 is to confirm the efficacy and safety of levilimab 648 mg IV Q4W in combination with methotrexate and levilimab 324 mg SC Q2W in combination with methotrexate in subjects with active rheumatoid arthritis, resistant to methotrexate monotherapy.

Start Date07 Dec 2022

Sponsor / Collaborator

Biocad CJSC

NCT04397562

/ CompletedPhase 3

A Multicenter, Randomized, Double-blind, Placebo-controlled, Adaptively Designed Clinical Trial of the Efficacy and Safety of Levilimab (BCD-089) in Patients With Severe COVID-19

The objective: to study the efficacy and safety of levilimab in subjects with severe COVID-19.

Start Date29 Apr 2020

Sponsor / Collaborator

Biocad CJSC

NCT04227366

/ CompletedPhase 3

An International, Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Study of the Efficacy and Safety of BCD-089 (JSC BIOCAD, Russia) in Combination With Methotrexate in Patients With Active Rheumatoid Arthritis

BCD-089 is the original therapeutic monoclonal antibody binding the alpha subunit of the IL-6 receptor.
The aim of the study is to demonstrate the efficacy and safety of BCD-089 in combination with methotrexate in patients with active rheumatoid arthritis resistant to monotherapy with methotrexate.

Start Date19 Nov 2019

Sponsor / Collaborator

Biocad CJSC

100 Clinical Results associated with Levilimab

100 Translational Medicine associated with Levilimab

100 Patents (Medical) associated with Levilimab

Literatures (Medical) associated with Levilimab

01 Oct 2024·Doklady Biochemistry and Biophysics

Efficacy and Safety of Levilimab in Combination with Methotrexate in Patients with Active Rheumatoid Arthritis: 56-Week Results of Phase III Randomized Double-Blind Placebo-Controlled Trial SOLAR

Article

Author: Kundzer, E V ; Popova, T A ; Mazurov, V I ; Plotnikova, A V ; Vinogradova, I B ; Dokukina, E A ; Tciupa, O A ; Linkova, Yu N ; Eremeeva, A V ; Povarova, T V ; Lila, A M ; Smakotina, S A ; Antipova, O V ; Korolev, M A ; Kropotina, T V ; Nesmeyanova, O B ; Kastanayan, A A ; Puntus, E V ; Prystrom, A M ; Nasonov, E L ; Zinkina-Orikhan, A V ; Krechikova, D G ; Shilova, L N ; Raskina, T A ; Lutckii, A A ; Pukhtinskaia, P S ; Plaksina, T V ; Soroka, N F

OBJECTIVES:

. To evaluate the efficacy and safety of levilimab in combination with methotrexate (MTX) in subjects with MTX resistant active RA.

MATERIALS AND METHODS:

: The study was conducted at 21 clinical sites in Russia and Belarus. All randomized subjects have completed the study between November 2019 and October 2021. Adult subjects (154) aged ≥18 years with confirmed diagnosis of RA¹ were randomly assigned (2 : 1) to receive either levilimab (162 mg, SC, QW) + MTX (n = 102) or placebo + MTX (n = 52). After W24 of the study all subjects continued to receive open label levilimab. Subjects who have achieved DAS28-CRP ≤ 2.6 at W24 were switched to maintenance (Q2W) regimen of levilimab at W28 (LVL QW/Q2W and PBO/LVL Q2W arms). Those with DAS28-CRP > 2.6 at W28 continued with QW regimen (LVL QW and PBO/LVL QW arm). The PBO/LVL Q2W arm contained only one subject, thus not included in the analysis. The efficacy analysis was performed in a population of all randomized subjects. Those with missing data due to study discontinuation or rescue therapy prescription were considered non-responders. Otherwise, the analysis was performed on complete cases. Safety was assessed through monitoring of adverse events (AEs) in a population of those, who received at least on dose of LVL (n = 152).

RESULTS:

: Better response to treatment was observed in LVL QW/Q2W as it composed of those who reach DAS28-CRP ≤ 2.6 at W24. At this time point 15/27 (55.6%) of them achieved ACR70; 23/27 (85.2%) achieved DAS28-CRP remission (<2.6) and 7/27 (25.9%) achieved ACR/EULAR2011 remission of RA. After switching to LVL Q2W, rates of ACR70 and DAS28-CRP<2.6 did not significantly changed until W52: 17/27 (63.0%) and 21/27 (77.8%), respectively, yet the proportion of subject with ACR/EULAR 2011 remission further increased and reached 12/27 (44.4%). LVL QW arm was diminished by subjects who achieved high response to treatment at W24 and composed LVL QW/Q2W arm. Thus, ACR70, and remissions rate in this arm was close to zero at W24. However, continuation of LVL QW in those who not achieved DAS28-CRP ≤ 2.6 at W24 induced ACR70 response in 37/75 (36.0%), DAS28-CRP remission in 35/75 (46.7%) and ACR/EULAR 2011 remission in 8/75 (10.7%) at W52. The most common adverse events (reported in ≥5% of subjects) were blood cholesterol increase (30.3%), ALT increase (23.0%), lymphocyte count decrease (17.1%), ANC decrease (16.4%), blood triglycerides increase (13.8%), bilirubin increase (11.2%), AST increase (9.9%), WBC decrease (9.9%), IGRA with Mycobacterium tuberculosis antigen positive (7.2%), and injection site reactions (5.9%). No deaths occurred.

CONCLUSIONS:

: Open label period confirmed the lasting efficacy and safety of levilimab in combination with MTX in subjects with MTX resistant active RA and suggested the possibility of switching to levilimab maintenance regimen (once every 2 weeks) (Q2W) in those who achieved remission of RA at week 24.

01 Jan 2023·Annals of the rheumatic diseases

Efficacy of synthetic and biological DMARDs: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis

Review

Author: Sepriano, Alexandre ; Verschueren, Patrick ; Edwards, Christopher John ; de Souza, Savia ; Caporali, Roberto ; Stamm, Tanja A ; Aletaha, Daniel ; van der Heijde, Désirée ; Smolen, Josef S ; Landewé, Robert B M ; Kerschbaumer, Andreas ; Hyrich, Kimme L ; Winthrop, Kevin L ; Pope, Janet E ; Schoones, Jan W ; Bergstra, Sytske Anne ; Takeuchi, Tsutomu

Objectives:

To update the evidence on efficacy of DMARDs (disease-modifying antirheumatic drugs) and inform the taskforce of the 2022 update of the European Alliance of Associations for Rheumatology (EULAR) recommendations for management of rheumatoid arthritis (RA).

Methods:

This systematic literature review (SLR) investigated the efficacy of conventional synthetic (cs), biological (b), biosimilar and targeted synthetic (ts)DMARDs in patients with RA. Medline, EMBASE, Cochrane CENTRAL and Web of Science were used to identify all relevant articles published since the previous update in 2019 to 14 January 2022.

Results:

Of 8969 search results, 169 articles were selected for detailed review and 47 were finally included. Trials investigated the efficacy of csDMARDs, bDMARDs and tsDMARDs, DMARD switching, tapering and trials investigating different treatment strategies. The compounds investigated were csDMARDs (methotrexate (MTX), leflunomide, sulfasalazine, hydroxychloroquine), bDMARDs (abatacept, adalimumab, certolizumab-pegol, denosumab, etanercept, infliximab, levilimab, olokizumab, opineracept, rituximab, sarilumab, tocilizumab) and tsDMARDs (baricitinib, filgotinib, tofacitinib, upadacitinib). The efficacy of csDMARDs+ short-term glucocorticoids in early RA was confirmed and similar to bDMARD+MTX combination therapy. Interleukin-6 pathway inhibition was effective in trials on olokizumab and levilimab. Janus kinase inhibitor (JAKi) was efficacious in different patient populations. After insufficient response to JAKi, patients could respond to TNFi treatment. Tapering of DMARDs was feasible for a proportion of patients, who were able to taper therapy while remaining in low disease activity or remission.

Conclusion:

The results of this SLR, together with one SLR on safety of DMARD and one on glucocorticoids, informed the taskforce of the 2022 update of the EULAR recommendations for pharmacological management of RA.

01 Jan 2021·mAbsQ2 · MEDICINE

Antibodies to watch in 2021

Q2 · MEDICINE

Review

Author: Reichert, Janice M. ; Kaplon, Hélène

In this 12^th annual installment of the Antibodies to Watch article series, we discuss key events in antibody therapeutics development that occurred in 2020 and forecast events that might occur in 2021. The coronavirus disease 2019 (COVID-19) pandemic posed an array of challenges and opportunities to the healthcare system in 2020, and it will continue to do so in 2021. Remarkably, by late November 2020, two anti-SARS-CoV antibody products, bamlanivimab and the casirivimab and imdevimab cocktail, were authorized for emergency use by the US Food and Drug Administration (FDA) and the repurposed antibodies levilimab and itolizumab had been registered for emergency use as treatments for COVID-19 in Russia and India, respectively. Despite the pandemic, 10 antibody therapeutics had been granted the first approval in the US or EU in 2020, as of November, and 2 more (tanezumab and margetuximab) may be granted approvals in December 2020.* In addition, prolgolimab and olokizumab had been granted first approvals in Russia and cetuximab saratolacan sodium was first approved in Japan. The number of approvals in 2021 may set a record, as marketing applications for 16 investigational antibody therapeutics are already undergoing regulatory review by either the FDA or the European Medicines Agency. Of these 16 mAbs, 11 are possible treatments for non-cancer indications and 5 are potential treatments for cancer. Based on the information publicly available as of November 2020, 44 antibody therapeutics are in late-stage clinical studies for non-cancer indications, including 6 for COVID-19, and marketing applications for at least 6 (leronlimab, tezepelumab, faricimab, ligelizumab, garetosmab, and fasinumab) are planned in 2021. In addition, 44 antibody therapeutics are in late-stage clinical studies for cancer indications. Of these 44, marketing application submissions for 13 may be submitted by the end of 2021. *Note added in proof on key events announced during December 1-21, 2020: margetuximab-cmkb and ansuvimab-zykl were approved by FDA on December 16 and 21, 2020, respectively; biologics license applications were submitted for ublituximab and amivantamab.

News (Medical) associated with Levilimab

01 Dec 2023

·synapse.patsnap.com

Deciphering IL-6 Inhibitors: Your Guide to Rapidly Accessing the Newest Advances

IL-6, or Interleukin-6, is a cytokine that plays a crucial role in the human body's immune response and inflammation regulation. It is produced by various cells, including immune cells, and acts as a signaling molecule to stimulate the immune system during infection or injury. IL-6 also plays a role in the development and differentiation of immune cells, such as B cells and T cells. However, excessive or prolonged IL-6 production can lead to chronic inflammation and contribute to the pathogenesis of various diseases, including autoimmune disorders and certain cancers. Therefore, understanding and regulating IL-6 levels is of great importance in the pharmaceutical industry for the development of targeted therapies. IL-6 Inhibitors is relevant to many inflammatory diseases and cancers. The first approved medication in this class was tocilizumab (Actemra), an antibody directed against the IL-6 receptor. This was followed by siltuximab (Sylvant), which is directed against IL-6 itself. Sarilumab was approved by the US FDA in 2017 for rheumatoid arthritis. Several other agents are in clinical trials, including olokizumab (CDP6038), elsilimomab, clazakizumab (BMS-945429, ALD518), sirukumab (CNTO 136), levilimab (BCD-089), and CPSI-2364. Looking ahead, IL-6 inhibitors are expected to continue to play a significant role in the treatment of various diseases. They have shown promising results in treating serious COVID-19 cases2 and are also used widely for the treatment of rheumatoid arthritis2. The IL-6 inhibitors market is projected to grow at a CAGR of 10.9%, increasing from US$ 33.3 Billion in 2023 to US$ 93.3 Billion by 20333. However, the emergence of resistance and the lack of an effective reversal drug when bleeding occurs are challenges that need to be addressed. Ongoing research and development efforts are focused on addressing these issues and expanding the clinical applications of IL-6 inhibitors. Based on the analysis of the data, the current competitive landscape for target IL-6 is characterized by the presence of multiple companies with varying stages of development and a wide range of indications. Bristol Myers Squibb Co. stands out as the company with the highest stage of development, with multiple approved drugs and ongoing clinical trials. Small molecule drugs, molecular glues, and monoclonal antibodies are the most rapidly progressing drug types under the target IL-6. The United States, European Union, and China are the leading countries/locations in terms of development, with China showing significant progress. Overall, the target IL-6 presents a competitive landscape with diverse players and promising future development potential. How do they work?IL-6 inhibitors are a type of medication that target and inhibit the activity of interleukin-6 (IL-6), a cytokine involved in the immune response and inflammation. From a biomedical perspective, IL-6 inhibitors are used in the treatment of various inflammatory conditions such as rheumatoid arthritis, systemic juvenile idiopathic arthritis, and Castleman's disease. These inhibitors work by blocking the binding of IL-6 to its receptor, thereby reducing the inflammatory response mediated by IL-6. By inhibiting IL-6, these medications help alleviate symptoms and reduce disease progression in patients with IL-6-mediated inflammatory disorders List of IL-6 InhibitorsThe currently marketed IL-6 inhibitors include: SiltuximabPomalidomidePirfenidoneLenalidomideOlokizumabSirukumabSodium PyruvateClazakizumabRO-7200220ZiltivekimabFor more information, please click on the image below. What are IL-6 inhibitors used for?IL-6 inhibitors are used in the treatment of various inflammatory conditions such as rheumatoid arthritis, systemic juvenile idiopathic arthritis, and Castleman's disease. For more information, please click on the image below to log in and search. How to obtain the latest development progress of IL-6 inhibitors?In the Synapse database, you can keep abreast of the latest research and development advances of IL-6 inhibitors anywhere and anytime, daily or weekly, through the "Set Alert" function. Click on the image below to embark on a brand new journey of drug discovery!

100 Deals associated with Levilimab

External Link

KEGG	Wiki	ATC	Drug Bank
D12748	-	L04AC25	DB16387

R&D Status

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Indication	Country/Location	Organization	Date
Rheumatoid Arthritis	Russia	Biocad CJSC	08 Jun 2021
COVID-19	Russia	Biocad CJSC	04 Jun 2020

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04397562 (SOLAR, EULAR2022)	Phase 3	Rheumatoid Arthritis	154	Levilimab 162 mg, SC + MTX	fhtsvfrdgj(wppuczarnl) = jcxsdulghp rcakbnunzr (clnmkijbsa ) View more	Positive	01 Jun 2022
NCT04397562 (CORONA, Pubmed) Manual	Phase 3	COVID-19	217	SOC+levilimab	dqflfwehfg(ubsqhridbb) = ftcauhawsu htcuumfusf (evqeswhmmb )	Positive	01 Dec 2021
				Placebo+SOC	dqflfwehfg(ubsqhridbb) = rfspyymijc htcuumfusf (evqeswhmmb )
NCT04397562 (SOLAR, EULAR2021)	Phase 3	Rheumatoid Arthritis	154	Levilimab + MTX	tjxexsjzjb(qqyhjehclg) = xuxkuunvjf islhrlvxmx (hahnwweqrw ) View more	Positive	02 Jun 2021
				Placebo + MTX	tjxexsjzjb(qqyhjehclg) = llfojejkpk islhrlvxmx (hahnwweqrw ) View more
NCT04397562 (CORONA, EULAR2021)	Phase 3	COVID-19 Erythrocyte sedimentation rate (ESR) \| C-reactive protein (CRP) \| IL-6	217	Levilimab	qmcbpzuxgk(mmkhgoczgr) = dxohpjhbrj kphwbqavna (xyxbijgkgv ) View more	Positive	02 Jun 2021
				Placebo	qmcbpzuxgk(mmkhgoczgr) = mfltihsrco kphwbqavna (xyxbijgkgv ) View more
NCT03103438 (CTgov)	Phase 1	Autoimmune Diseases \| Rheumatoid Arthritis	19	BCD-089 (Cohort 1)	yhqdbeafrm(zmqtfqxrlz) = orjqvnbjdu ffzjadbesw (ndjdhjjant, ztgeaazfdn - qdyengweqy) View more	-	26 Feb 2021
				BCD-089 (Cohort 2)	yhqdbeafrm(zmqtfqxrlz) = lfhitryhzw ffzjadbesw (ndjdhjjant, lilzswkvwd - jfneqaebtv) View more
NCT03455842 (AURORA, EULAR2019)	Phase 2	Rheumatoid Arthritis	105	BCD-089 QW+MTX	pfhfxgjlem(pikgqgqcbc) = sprzvcvrrw jdrwafyrzv (iwznxkmclm ) View more	Positive	12 Jun 2019
				BCD-089 Q2W+MTX	pfhfxgjlem(pikgqgqcbc) = yathixbhmh jdrwafyrzv (iwznxkmclm ) View more

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