Delving into the Latest Updates on Tesidolumab with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Target

C5

Mechanism

C5 modulators(Complement C5 modulators)

Therapeutic Areas

Congenital DisordersEye DiseasesHemic and Lymphatic Diseases+ [2]

Active Indication-

Inactive Indication

Originator Organization

MorphoSys AG

Active Organization-

Inactive Organization

Novartis Pharmaceuticals Corp.Novartis Institutes for BioMedical Research GmbH & Co. KGAlcon Research Ltd.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Gene Sequence

Sequence Code 148002H

Source: *****

Sequence Code 148008L

Source: *****

This was a randomized, SoC-controlled, open-label, multi-center study in patients with TAM after hematopoietic precursor cell transplantation (HPCT) .
Study consisted of up to 28 days of screening period, 16 weeks treatment period that can be extended to 45 weeks.Approximately 40 patients was to be randomized to receive SoC or LFG316 plus SoC. Patients was included in the study if they have diagnosis of TAM and poor prognostic markers. This trial was terminated: LFG316, a monoclonal antibody inhibitor of complement factor 5 (C5), had been studied in seven patients with transplantation-associated microangiopathy (TAM). Due to low confidence of clinical benefit, this study was closed

Start Date22 Apr 2016

Sponsor / Collaborator

Novartis Pharmaceuticals Corp.

100 Clinical Results associated with Tesidolumab

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100 Translational Medicine associated with Tesidolumab

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100 Patents (Medical) associated with Tesidolumab

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7

Literatures (Medical) associated with Tesidolumab

01 May 2024·International Journal of Laboratory Hematology

Complement inhibition in paroxysmal nocturnal hemoglobinuria: From biology to therapy

Review

Author: Fattizzo, Bruno ; Versino, Francesco

AbstractComplement inhibitors are the mainstay of paroxysmal nocturnal hemoglobinuria (PNH) treatment. The anti‐C5 monoclonal antibody eculizumab was the first treatment to improve hemolysis, thrombotic risk, and survival in PNH although at the price of a life‐long intravenous fortnightly drug. Additionally, suboptimal response may occur in up to 2/3 of patients with persistent anemia due to incomplete control of intravascular hemolysis, development of upstream C3‐mediated extravascular hemolysis (EVH), or concomitant bone marrow failure. Ravulizumab, a longer half‐life anti‐C5 developed from eculizumab, administered every 8 weeks, improved patient convenience, and reduced pharmacokinetic breakthrough hemolysis (BTH) by establishing more stable anti‐C5 concentrations. More recently, several other anti‐C5 compounds (crovalimab, pozelimab, tesidolumab, cemdisiran, zilucoplan, and coversin) are on study in clinical trials. Upstream inhibition of complement cascade was also explored with the anti‐C3 pegcetacoplan, and with the alternative pathway inhibitors iptacopan (anti‐factor B) and danicopan (anti‐factor D). These drugs efficiently target EVH and are able to improve anemia and transfusion need in suboptimal responders to anti‐C5. The route and schedule of administration (twice weekly subcutaneously for pegcetacoplan and twice or thrice oral daily dosing for iptacopan and danicopan, respectively) are very convenient but pose novel issues regarding adherence. Additionally, both anti‐C5 and upstream inhibitors do not resolve the unmet need of pharmacodynamic BTH events due to complement amplifying conditions such as infections, traumas, and surgery. In this review, we will recapitulate PNH physiopathology, clinical presentation, and diagnosis and describe available and developing drugs that will lead to a precision medicine approach for this rare though heterogenous disease.

01 Oct 2022·CPT: Pharmacometrics & Systems Pharmacology

Physiologically‐based pharmacokinetic modeling of immunoglobulin and antibody coadministration in patients with primary human immunodeficiency

Article

Author: Kakkar, Tarundeep ; Salerno, Sara N. ; Deng, Rong

AbstractIntravenous immunoglobulin (IVIG) (2000 mg/kg) increased the clearance of the mouse monoclonal antibody 7E3, directed against platelet integrin IIb/IIIa (alpha IIb beta 3, CD41/CD61) in rodents. We wanted to investigate the effect of IVIG on clearance of monoclonal antibodies in humans as there is extremely limited data regarding this interaction in the literature. Using the tyrosine protein kinase KIT anti‐cluster of differentiation 117 (c‐Kit) humanized monoclonal antibody (JSP191) as a case study, we used physiologically‐based pharmacokinetic (PBPK) modeling to evaluate the pharmacokinetic interaction between monoclonal antibodies and IVIG at doses (300–600 mg/kg) administered to patients with primary human immunodeficiency (PI). We first characterized the interaction between monoclonal antibodies and IVIG in PK‐Sim®/MoBi® using published literature data, including the following: IVIG plus 7E3 in mice and rats and IVIG plus the human anti‐C5 monoclonal antibody tesidolumab in adults with end‐stage renal disease. We next developed a PBPK model using digitized data for JSPI91 alone in older adults with myelodysplastic syndrome and acute myeloid leukemia and in pediatric patients with severe combined immunodeficiency (SCID). Finally, we simulated the impact of IVIG (300–2000 mg/kg) coadministration with JSP191 on the area under the curve of JSP191 in patients with SCID. Model predictions were within 1.5‐fold of observed values for 7E3 plus IVIG and tesidolumab plus IVIG as well as for JSP191 administered alone. Based on our simulations, IVIG doses ≥500 mg exceeded the 80%–125% no‐effect boundaries. IVIG treatment with monoclonal antibodies in patients with PI may result in a clinically significant interaction depending on the IVIG dose administered and the exposure–response relationship for the specific monoclonal antibody.

01 Sep 2021·Annals of SurgeryQ1 · MEDICINE

Anti-C5 Antibody Tesidolumab Reduces Early Antibody-mediated Rejection and Prolongs Survival in Renal Xenotransplantation

Q1 · MEDICINE

Article

Author: Faber, David A ; Burlak, Christopher ; Vianna, Rodrigo M ; Tector, Alfred J ; Lovasik, Brendan P ; Breeden, Cynthia ; Estrada, Jose L ; Reyes, Luz M ; Adams, Andrew B ; Tector, Matthew F

Objective:Pig-to-primate renal xenotransplantation is plagued by early antibody-mediated graft loss which precludes clinical application of renal xenotransplantation. We evaluated whether temporary complement inhibition with anti-C5 antibody Tesidolumab could minimize the impact of early antibody-mediated rejection in rhesus monkeys receiving pig kidneys receiving costimulatory blockade-based immunosuppression.Methods:Double (Gal and Sda) and triple xenoantigen (Gal, Sda, and SLA I) pigs were created using CRISPR/Cas. Kidneys from DKO and TKO pigs were transplanted into rhesus monkeys that had the least reactive crossmatches. Recipients received anti-C5 antibody weekly for 70 days, and T cell depletion, anti-CD154, mycophenolic acid, and steroids as baseline immunosuppression (n = 7). Control recipients did not receive anti-C5 therapy (n = 10).Results:Temporary anti-C5 therapy reduced early graft loss secondary to antibody-mediated rejection and improved graft survival (P < 0.01). Deleting class I MHC (SLA I) in donor pigs did not ameliorate early antibody-mediated rejection (table). Anti-C5 therapy did not allow for the use of tacrolimus instead of anti-CD154 (table), prolonging survival to a maximum of 62 days.Conclusion:Inhibition of the C5 complement subunit prolongs renal xenotransplant survival in a pig to non-human primate model.

100 Deals associated with Tesidolumab

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB11926

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hemoglobinuria, Paroxysmal	Phase 2	LT	Novartis Pharmaceuticals Corp.	09 Sep 2015
Hemoglobinuria, Paroxysmal	Phase 2	CZ	Novartis Pharmaceuticals Corp.	09 Sep 2015
Non-infectious posterior uveitis	Phase 2	US	Novartis Pharmaceuticals Corp.	20 Dec 2012
Non-infectious posterior uveitis	Phase 2	GB	Novartis Pharmaceuticals Corp.	20 Dec 2012
Uveitis, Intermediate	Phase 2	US	Novartis Pharmaceuticals Corp.	20 Dec 2012
Uveitis, Intermediate	Phase 2	GB	Novartis Pharmaceuticals Corp.	20 Dec 2012
Wet age-related macular degeneration	Phase 2	US	Novartis Pharmaceuticals Corp.	01 Feb 2012
Wet Macular Degeneration	Phase 2	US	Novartis Pharmaceuticals Corp.	01 Feb 2012
Age Related Macular Degeneration	Phase 2	US	Novartis Pharmaceuticals Corp.	25 Jan 2012
Geographic Atrophy	Phase 2	US	Novartis Pharmaceuticals Corp.	25 Jan 2012

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02534909 (CTgov)	Phase 2	Hemoglobinuria, Paroxysmal	10	LFG316+LNP023	hzzqottwvq(qflnsgkkcp) = jvhabzdakn kbjkpdujxz (rwnyxgrzie, depsvixwrw - kgkictzlay) View more	-	01 Nov 2024
NCT02515942 (CTgov)	Phase 2	Geographic Atrophy	114	CLG561 (CLG561)	njhiffgwke(vbotsxnjuy) = rnikvgmscc awjhioibuh (lhymjnsias, pwajudzgqy - qlcfygsuvc) View more	-	19 Dec 2018
NCT02515942 (CTgov)	Phase 2	Geographic Atrophy	114	LFG316+CLG561 (CLG561+LFG316)	njhiffgwke(vbotsxnjuy) = yrfkswpcmo awjhioibuh (lhymjnsias, zfmznyzdux - ksxdjwynid) View more	-	19 Dec 2018
NCT01526889 (CTgov)	Phase 2	Non-infectious posterior uveitis \| Uveitis, Intermediate	25	Conventional Therapy	zjxndmwmvn(sfeunifgtb) = qocodhaksh jrjlksdcft (sfuypdopqn, pfdrbtceyh - ktodenfxkl) View more	-	31 Oct 2018