Delving into the Latest Updates on Sirukumab with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Shirukumabu, Sirukumab (genetical recombination) (JAN), Sirukumab (USAN)

+ [3]

Target

IL-6

Mechanism

IL-6 inhibitors(Interleukin-6 inhibitors)

Therapeutic Areas

Immune System DiseasesNervous System DiseasesCardiovascular Diseases+ [5]

Active Indication-

Inactive Indication

AsthmaCOVID-19Depressive Disorder, Major+ [6]

Originator Organization

GSK Plc

Active Organization-

Inactive Organization

Janssen Research & Development LLC

GSK PlcCentocor Research & Development, Inc.

+ [3]

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

Regulation-

Gene Sequence

Sequence Code 9909244H

Source: *****

Sequence Code 9909249L

Source: *****

Sirukumab is a human anti-IL-6 monoclonal antibody that selectively binds to the cytokine with high affinity that may have therapeutic benefit in the treatment of polymyalgia rheumatica (PMR) by interrupting multiple pathogenic pathways. Sirukumab inhibits IL-6-mediated signal transducer and activator of transcription 3 (STAT3) phosphorylation, resulting in the inhibition of the biological effect of IL-6. This study will evaluate the efficacy and safety of sirukumab to characterize the benefit-to-risk profile of sirukumab in the treatment of active PMR. The study will be conducted in 2 parts (Part A and Part B) and consists of the following phases: Screening phase, Part A: 52-week double-blind treatment phase, Part B: 52-week extension phase with no study drug administration and a 16-week follow-up phase if applicable.
Approximately 150 subjects with a diagnosis of PMR and active disease within 6 weeks of baseline will be randomized into Part A, the 52-week double-blind treatment phase, to receive one of two doses of sirukumab or placebo, each in addition to a pre-specified prednisone taper. The efficacy and safety of sirukumab in sustaining remission will be assessed at Week 52. Subjects completing Part A of the study who are in clinical remission will be eligible to enter Part B, the 52-week extension phase, designed to investigate the long-term maintenance of remission and safety following cessation of sirukumab treatment and to assess long-term corticosteroid use. Subjects will need to have follow-up safety evaluations for at least 16 weeks after receiving the last dose of study drug, applicable for those who have withdrawn prematurely from the study or who have completed Part A but are not eligible for Part B.

Start Date15 Mar 2018

Sponsor / Collaborator

GSK Plc

NCT02794519 / WithdrawnPhase 2

205076: A Phase II, Multicenter, Randomized, Double-blind (Sponsor-unblind), Placebo- Controlled, Parallel Group Trial to Evaluate the Efficacy and Safety of Sirukumab in Subjects With Severe, Poorly Controlled Asthma

Sirukumab is a fully human anti interleukin (IL)-6 immunoglobulin G1-kappa monoclonal antibody (MAb) which is in development for the treatment of rheumatoid arthritis (RA). The continuing unmet need in subjects with asthma refractory to corticosteroid therapy and increased understanding of asthma pathogenesis have stimulated the development of targeted biologics based on predictive biomarkers. The majority of approaches to date have targeted T Helper 2 (Th2) cytokines or their downstream effects. Targeting IL-6 in severe asthma represents an unprecedented approach that has potential to address non-Th2 drivers of severe asthma. This multicenter, randomized, double-blind (sponsor-unblind), placebo-controlled, parallel group study will investigate the efficacy of sirukumab compared to placebo in subjects having uncontrolled severe asthma despite use of high dose inhaled corticosteroid (ICS) in combination with long-acting Beta-agonist (LABA). The study will employ a variable treatment period for individual subjects. Dosing will continue every 4 weeks until week 44 (inclusive), or until 24 weeks after the final subject has been randomized, whichever the sooner. Upon receiving the final dose of study medicine or placebo, subjects will enter a 16 week Follow Up period. Overall, the duration of participation for subjects who complete the full 44-week treatment period and Follow Up period may be up to 64 weeks. Approximately 175 subjects will be randomized such that 140 evaluable subjects complete the study.

Start Date23 Sep 2016

Sponsor / Collaborator

GSK Plc

100 Clinical Results associated with Sirukumab

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100 Translational Medicine associated with Sirukumab

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100 Patents (Medical) associated with Sirukumab

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78

Literatures (Medical) associated with Sirukumab

01 Jan 2024·European journal of medicinal chemistry

Mitochondria-targeted pentacyclic triterpene NIR-AIE derivatives for enhanced chemotherapeutic and chemo-photodynamic combined therapy

Article

Author: Zhang, Xuewei ; Zheng, Jinhong ; Wang, Xiang ; Wang, Jinzhi ; Dong, Mingming ; Zheng, Guoxing ; Lin, Liyin ; Yan, Kang ; Huang, Zhaopeng

Complexes formed by combining pentacyclic triterpenes (PTs) with Aggregation-Induced Emission luminogens (AIEgens), termed pentacyclic triterpene-aggregation induced emission (PT-AIEgen) complexes, merge the chemotherapeutic properties of PTs with the photocytotoxicity of AIEgens. In this study, we synthesized derivatives by connecting three types of triphenylamine (TPA) pyridinium derivatives with three common pentacyclic triterpenes. Altering the connecting group between the electron donor TPA and the electron acceptor pyridinium resulted in increased production of reactive oxygen species (ROS) by PT-AIEgens and a red-shift in their fluorescence emission spectra. Importantly, the fluorescence emission spectra of BA-3, OA-3, and UA-3 extended into the near-infrared (NIR) range, enabling NIR-AIE imaging of the sites where the derivatives aggregated. The incorporation of the pyridinium structure improved the mitochondrial targeting of PT-AIEgens, enhancing mitochondrial pathway-mediated cell apoptosis and improving the efficiency of chemotherapy (CT) and chemo-photodynamic combined therapy (CPCT) both in vivo and in vitro. Cellular fluorescence imaging demonstrated rapid cellular uptake and mitochondrial accumulation of BA-1 (-2, -3). Cell viability experiments revealed that BA-1 (-2), OA-1 (-2), and UA-1 (-2) exhibited superior CT cytotoxicity compared to their parent drugs, with BA-1 showing the most potent inhibitory effect on HeLa cells (IC₅₀ = 1.19 μM). Furthermore, HeLa cells treated with BA-1 (1 μM), BA-2 (1.25 μM), and BA-3 (1 μM) exhibited survival rates of 2.99 % ± 0.05 % μM, 5.92 % ± 2.04 % μM, and 2.53 % ± 0.73 % μM, respectively, under white light irradiation. Mechanistic experiments revealed that derivatives induced cell apoptosis via the mitochondrial apoptosis pathway during both CT and CPCT. Remarkably, BA-1 and BA-3 in CPCT inhibited cancer cell proliferation in an in vivo melanoma mouse xenograft model. These results collectively encourage further research of PT-AIEgens as potential anticancer agents.

01 Jan 2024·BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy

Targeting IL-6 or IL-6 Receptor in Rheumatoid Arthritis: What Have We Learned?

Review

Author: Burmester, Gerd R ; Feist, Eugen ; Avci, Ali Berkant

The use of different pathways in the treatment of rheumatoid arthritis has led to a significant decrease in the number of treatment-resistant patients. In this context, interleukin (IL)-6 inhibition has filled an important gap in rheumatoid arthritis treatment with its effectiveness and safety in both monotherapy and combinations. The process of IL-6 inhibition initiated with IL-6 receptor blockers has prompted questions regarding the potential impact and safety of different inhibitions of this pathway, such as the direct blockade of IL-6. Following the termination of the development of sirukumab because of mortality data in early studies, the investigation of olokizumab, which targets a different region of the IL-6 cytokine, has renewed the hope in this area and the safety concerns have been largely alleviated by the open-label extension data. In addition, the efficacy and safety of tocilizumab and sarilumab have led to a rapid investigation of biosimilars and new potent IL-6 receptor blockers. A comprehensive understanding of mechanisms of this pathway with further long-term clinical data and basic research may provide a decisive impact on selecting the appropriate mechanism as the first choice in personalized treatments.

14 Sep 2023·Cancer investigation

Drug Repurposing Analysis for Colorectal Cancer through Network Medicine Framework: Novel Candidate Drugs and Small Molecules

Article

Author: Unal, Ulku ; Gov, Esra

This study aimed to reveal the drug-repurposing candidates for colorectal cancer (CRC) via drug-repurposing methods and network biology approaches. A novel, differentially co-expressed, highly interconnected, and co-regulated prognostic gene module was identified for CRC. Based on the gene module, polyethylene glycol (PEG), gallic acid, pyrazole, cordycepin, phenothiazine, pantoprazole, cysteamine, indisulam, valinomycin, trametinib, BRD-K81473043, AZD8055, dovitinib, BRD-A17065207, and tyrphostin AG1478 presented as drugs and small molecule candidates previously studied in the CRC. Lornoxicam, suxamethonium, oprelvekin, sirukumab, levetiracetam, sulpiride, NVP-TAE684, AS605240, 480743.cdx, HDAC6 inhibitor ISOX, BRD-K03829970, and L-6307 are proposed as novel drugs and small molecule candidates for CRC.

100 Deals associated with Sirukumab

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External Link

KEGG	Wiki	ATC	Drug Bank
D10080	Sirukumab	L04AC15	DB11803

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Polymyalgia Rheumatica	Phase 3	-	GSK Plc	15 Mar 2018
Giant Cell Arteritis	Phase 3	US	GSK Plc	16 Oct 2015
Giant Cell Arteritis	Phase 3	AU	GSK Plc	16 Oct 2015
Giant Cell Arteritis	Phase 3	BE	GSK Plc	16 Oct 2015
Giant Cell Arteritis	Phase 3	BG	GSK Plc	16 Oct 2015
Giant Cell Arteritis	Phase 3	FR	GSK Plc	16 Oct 2015
Giant Cell Arteritis	Phase 3	DE	GSK Plc	16 Oct 2015
Giant Cell Arteritis	Phase 3	HU	GSK Plc	16 Oct 2015
Giant Cell Arteritis	Phase 3	IT	GSK Plc	16 Oct 2015
Giant Cell Arteritis	Phase 3	NL	GSK Plc	16 Oct 2015

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04380961 (CTgov)	Phase 2	COVID-19	212	Sirukumab (Sirukumab + SOC)	lxfwrwbizy(tyfequymua) = roiuejhvnl gwszssejxo (qyswdxuunb, jklqjwvvkp - lgzjzwjgbf) View more	-	21 Jun 2022
				Placebo (Placebo + SOC)	lxfwrwbizy(tyfequymua) = dsnomheiar gwszssejxo (qyswdxuunb, gjhphujtjw - afznygwuve) View more
NCT02531633 (Pubmed \| Rheumatol Ther) Manual	Phase 3	Giant Cell Arteritis	161	Sirukumab	iwkbqlcuqn(nhojngbnni) = xwkfxrgipf abvuqmafvz (zqtgfeqybl )	Positive	01 Dec 2020
				Placebo	iwkbqlcuqn(nhojngbnni) = jblnbjbrmb abvuqmafvz (zqtgfeqybl )
NCT02473289 (CTgov)	Phase 2	Depressive Disorder, Major	193	Placebo	gjfodfpfji(jjotoxxlnf) = vhispjftsm nxokocsgjs (wsuphsqrzg, ndtxhmoisl - xpauqeodpu) View more	-	11 Jun 2019
NCT01856309 (CTgov)	Phase 3	Rheumatoid Arthritis	1,820	Placebo (Placebo to 50 mg q4w Due to EE/LE/CO)	bffppbnkhb(gmpzonrlen) = dhvdloxzlr zqrcnxxcwp (cjsjtpmuww, nxdqmapfrr - agkyobhplo) View more	-	06 May 2019
				Placebo (Placebo to 100 mg q2w Due to EE/LE/CO)	bffppbnkhb(gmpzonrlen) = zxnhwseove zqrcnxxcwp (cjsjtpmuww, jkasxafutu - mzbmoopsmh) View more
NCT01689532 (Pubmed \| J Rheumatol) Manual	Phase 3	Rheumatoid Arthritis	122	Sirukumab (50 mg once every 4 weeks)	tsonwatdjj(wgsjryktpj) = kdsnmroopp eckjawvgjd (ctnnmmunxp )	Positive	07 Mar 2018
				Sirukumab (100 mg once every 2 weeks)	tsonwatdjj(wgsjryktpj) = rhkbpncnls eckjawvgjd (ctnnmmunxp )
NCT01604343 (SIRROUND-D, CTgov)	Phase 3	Rheumatoid Arthritis	1,670	Sirukumab	uvcoclscne(pwlugtjizf) = wwtbgvelem khipcltked (pjcbsjrxay, xbipwrerjz - jazrmmukow) View more	-	11 Jan 2018
NCT01604343 (SIRROUND-D, Pubmed)	Phase 3	Rheumatoid Arthritis	1,670	Sirukumab 100mg every 2 weeks	lgkayvvqxn(wcttbomljq) = zeqkiubokn bcxvtkztdl (ahcbluupnz )	Positive	01 Dec 2017
				Sirukumab 50mg every 4 weeks	lgkayvvqxn(wcttbomljq) = abeumauwxi bcxvtkztdl (ahcbluupnz )
NCT02019472 (SIRROUND-H, CTgov)	Phase 3	Rheumatoid Arthritis	559	Adalimumab (Adalimumab 40 mg)	kdligenvtg(dygkncjuxa) = capukotfde zurqjqvbzt (roqlphczge, giwkknaygt - jjwizyrjdg) View more	-	14 Sep 2017
				Sirukumab (Sirukumab 50 mg)	kdligenvtg(dygkncjuxa) = jzelpixbrr zurqjqvbzt (roqlphczge, cgsqgrksnc - ghxqnrfyuc) View more
SIRROUND (EULAR2017)	Phase 3	Rheumatoid Arthritis	2,926	SIR 50mg q4w	osfgxnwpjx(pgkoyqoeav) = qhbedylcnt qhqfqnnmvh (bmiyibtzsz ) View more	-	14 Jun 2017
				SIR 100mg q2w	osfgxnwpjx(pgkoyqoeav) = yuqygpymxp qhqfqnnmvh (bmiyibtzsz ) View more
SIRROUND-T (EULAR2017)	Phase 3	Rheumatoid Arthritis anti-tumor necrosis factor (TNF)	878	Sirukumab SC 50mg q4w	ymbckssztq(ouifzoykjw) = rbyszjcmhp xhdxjbxvze (ntqhmvjevy ) View more	-	14 Jun 2017
				Sirukumab SC 100mg q2w	ymbckssztq(ouifzoykjw) = dwhpkdirrb xhdxjbxvze (ntqhmvjevy ) View more