Delving into the Latest Updates on Edratide with Synapse

Overview

Basic Info

Drug Type

Synthetic peptide

Synonyms

Edratide (USAN/INN)

Target

APRIL x IFNγ x IL-1β x TNF-α x caspase 8

Mechanism

APRIL inhibitors(Tumor necrosis factor ligand superfamily member 13 inhibitors), IFNγ inhibitors(Interferon gamma inhibitors), IL-1β inhibitors(Interleukin-1 beta inhibitors)

+ [3]

Therapeutic Areas

Immune System DiseasesSkin and Musculoskeletal Diseases

Active Indication

Systemic Lupus Erythematosus

Inactive Indication

Sjogren's Syndrome

Originator Organization

Weizmann Institute of Science

Active Organization

Weizmann Institute of Science

Inactive Organization

Teva Pharmaceutical Industries Ltd.

XTL Biopharmaceuticals Ltd.

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC111H149N27O28

InChIKeyVXXZQHUWZSRPAM-CDJUQFLLSA-N

CAS Registry433922-67-9

Gene Sequence

Sequence Code 75657

Source: *****

ObjectiveTo evaluate the safety and efficacy of hCDR1 (Edratide) in patients with systemic lupus erythematosus (SLE).MethodsPatients (n=340) with SLE ≥4 ACR criteria (4–11, mean 7) with active disease (SLEDAI-2K of 6–12). Patients were on average 7.1 years post-diagnosis and their organ involvement was mainly musculoskeletal, mucocutaneous and haematologic. Placebo or Edratide was administered subcutaneously weekly at doses of 0.5, 1.0 or 2.5 mg. The co-primary endpoints were SLEDAI-2K SLE Disease Activity and Adjusted Mean SLEDAI (AMS) reduction in patients compared with controls using a landmark analysis. Secondary outcomes were improvement in British Isles Lupus Assessment Group (BILAG) Responder Index and medicinal flare analysis.ResultsEdratide was safe and well tolerated. The primary endpoints based solely on SLEDAI-2K and AMS were not met. The secondary predefined endpoint, BILAG, was met for the 0.5 mg Edratide arm in the intention to treat (ITT) cohort (N=316) (OR=2.09, p=0.03) with trends in the 1.0 and 2.5 mg doses. There was also a positive trend in the Composite SLE Responder Index of the ITT cohort. Post hoc analysis showed that the BILAG secondary endpoint was also met for the 0.5 mg Edratide for a number of subgroup dose levels, including low or no steroids, seropositivity and patients with 2 grade BILAG improvement.ConclusionsThe favourable safety profile and encouraging clinically significant effects noted in some of the endpoints support the need for additional longer term Edratide studies that incorporate recent advances in the understanding and treatment of SLE, including steroid treatment algorithms, and using a composite primary endpoint which is likely to include BILAG.Trial registration numberNCT00203151.

01 Nov 2014·Journal of AutoimmunityQ1 · MEDICINE

Novel approaches to the development of targeted therapeutic agents for systemic lupus erythematosus

Q1 · MEDICINE

Review

Author: Sthoeger, Zev ; Sharabi, Amir ; Mozes, Edna

Systemic lupus erythematosus (SLE) is a chronic multisystem disease in which various cell types and immunological pathways are dysregulated. Current therapies for SLE are based mainly on the use of non-specific immunosuppressive drugs that cause serious side effects. There is, therefore, an unmet need for novel therapeutic means with improved efficacy and lower toxicity. Based on recent better understanding of the pathogenesis of SLE, targeted biological therapies are under different stages of development. The latter include B-cell targeted treatments, agents directed against the B lymphocyte stimulator (BLyS), inhibitors of T cell activation as well as cytokine blocking means. Out of the latter, Belimumab was the first drug approved by the FDA for the treatment of SLE patients. In addition to the non-antigen specific agents that may affect the normal immune system as well, SLE-specific therapeutic means are under development. These are synthetic peptides (e.g. pConsensus, nucleosomal peptides, P140 and hCDR1) that are sequences of conserved regions of molecules involved in the pathogenesis of lupus. The peptides are tolerogenic T-cell epitopes that immunomodulate only cell types and pathways that play a role in the pathogenesis of SLE without interfering with normal immune functions. Two of the peptides (P140 and hCDR1) were tested in clinical trials and were reported to be safe and well tolerated. Thus, synthetic peptides are attractive potential means for the specific treatment of lupus patients. In this review we discuss the various biological treatments that have been developed for lupus with a special focus on the tolerogenic peptides.

01 Aug 2009·Journal of AutoimmunityQ1 · MEDICINE

Treatment of lupus patients with a tolerogenic peptide, hCDR1 (Edratide): Immunomodulation of gene expression

Q1 · MEDICINE

Article

Author: Heidy Zinger ; Amir Sharabi ; Edna Mozes ; Zev M. Sthoeger ; Molly Dayan ; Yair Molad ; Ilan Asher

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by dysregulation of cytokines, apoptosis, and B- and T-cell functions. The tolerogenic peptide, hCDR1 (Edratide), ameliorated the clinical manifestations of murine lupus via down-regulation of pro-inflammatory cytokines and apoptosis, up-regulation of the immunosuppressive cytokine TGF-beta, and the induction of regulatory T-cells. In the present study, gene expression was determined in peripheral blood mononuclear cells of 9 lupus patients that were treated for 26 weeks with either hCDR1 (five patients), or placebo (four patients). Disease activity was assessed by SLEDAI-2K and the BILAG scores. Treatment with hCDR1 significantly down-regulated the mRNA expression of the pathogenic cytokines IL-1beta, TNF-alpha, IFN-gamma, and IL-10, of BLyS (B-lymphocyte stimulator) and of the pro-apoptotic molecules caspase-3 and caspase-8. In contrast, the treatment up-regulated in vivo gene expression of both TGF-beta and FoxP3. Furthermore, hCDR1 treatment resulted in a significant decrease in SLEDAI-2K (from 8.0+/-2.45 to 4.4+/-1.67; P=0.02) and BILAG (from 8.2+/-2.7 to 3.6+/-2.9; P=0.03) scores. Thus, the tolerogenic peptide hCDR1, immunomodulates, in vivo, the expression of genes that play a role in SLE, consequently restoring the global immune dysregulation of lupus patients. Hence, hCDR1 has a potential role as a novel disease-specific treatment for lupus patients.

1

News (Medical) associated with Edratide

08 Nov 2022

·www.businesswire.com

Systemic Lupus Erythematosus (SLE) Update Bulletin 2022: Gain Insights on the Latest Events Happening in the Treatment Landscape - ResearchAndMarkets.com

DUBLIN--( BUSINESS WIRE )--The "Systemic Lupus Erythematosus (SLE): Update Bulletin #2" newsletter has been added to ResearchAndMarkets.com's offering. Gain new key opinion leader (KOL) insights on the latest events happening in Systemic Lupus Erythematosus (SLE) treatment landscape. Topics covered include expert opinions on the prospects of the Phase III BLISS-BELIEVE study which will assess co-administration of SC Benylsta (GSK's belimumab) and a single cycle of IV Rituxan/MabThera (rituximab; Roche/Biogen). The KOLs also imparted their views on the results of a Phase II study investigating Stelara (ustekinumab; Janssen Biotech) for the treatment of SLE, and the potential for XTL Biopharmaceuticals' edratide as well as Corbus Pharmaceuticals's anabasum. Business Questions: How do KOLs view the combination of belimumab and rituximab for the treatment of SLE? Do KOLs harbour any concerns about combining these two biologic agents? How do experts view the results of ustekinumab's Phase II study? What advantages does ustekinumab have over other pipeline SLE agents? How do KOLs perceive edratide's mechanism of action and preliminary trial results? How optimistic are KOLs about edratide's prospects as a treatment for SLE? Do KOLs perceive anabasum's mechanism of action to be promising? How do KOLs view this agent's safety profile? For more information about this newsletter visit https://www.researchandmarkets.com/r/rggx5q

100 Deals associated with Edratide

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External Link

KEGG	Wiki	ATC	Drug Bank
D03957	-	-	DB15272

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Sjogren's Syndrome	Phase 2	IL	XTL Biopharmaceuticals Ltd.	-
Systemic Lupus Erythematosus	Phase 2	EU	Teva Pharmaceutical Industries Ltd.	-
Systemic Lupus Erythematosus	Phase 2	-	Weizmann Institute of Science	-
Systemic Lupus Erythematosus	Phase 2	RU	Teva Pharmaceutical Industries Ltd.	-
Systemic Lupus Erythematosus	Preclinical	RU	Teva Pharmaceutical Industries Ltd.	-
Systemic Lupus Erythematosus	Preclinical	EU	Teva Pharmaceutical Industries Ltd.	-