Delving into the Latest Updates on DiaPep-277 with Synapse

Overview

Basic Info

Drug Type

Synthetic peptide

Synonyms

Target

HSPA14

Mechanism

HSPA14 modulators(heat shock protein family A (Hsp70) member 14 modulators)

Therapeutic Areas

Immune System DiseasesEndocrinology and Metabolic Disease

Active Indication-

Inactive Indication

Diabetes Mellitus, Type 1

Originator Organization

Weizmann Institute of Science

Active Organization-

Inactive Organization

Weizmann Institute of ScienceAndromeda Biotech Ltd.

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

Regulation-

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Gene Sequence

Sequence Code 89155

Source: *****

Type 1 diabetes is caused by an autoimmune process resulting in a selective destruction of the pancreatic insulin-secreting beta-cell. DiaPep277® is a small, lyophilized powder containing 24 Amino-acids. We have proved in former studies that DiaPep277® can slow down beta cells destruction in the pancreas and therefore decelerate the progress of Diabetes.
The objective of the study is to assess the efficacy and safety of administrating DiaPep277® in type 1 diabetes patients.

Start Date01 Jan 2015

Sponsor / Collaborator

Hadassah University Hospital

NCT01898286 / TerminatedPhase 3

Open-Label Study to Evaluate Long Term Safety and Treatment Effect of DiaPep277® in Subjects Who Have Completed Study 1001 (NCT01103284)

This is an extension study to evaluate the safety and tolerability of long-term treatment with DiaPep277® and to determine the long-term treatment effect of DiaPep277® on parameters of metabolic control and on preservation of beta-cell function in subjects who have long exposure to DiaPep277®.

Start Date01 Oct 2013

Sponsor / Collaborator

Andromeda Biotech Ltd.

NCT01460251 / TerminatedPhase 3IIT

OPen Label Study to Evaluate Long Term Treatment Effect of DiaPep277 in Patients Who Have Completed Study 901 and Study 910 (Extension to 901 Phase III Study

The study is an open-label extension study, offering patients who participated and completed previous studies 901 and 910 (an extension to 901) to continue treatment with DiaPep277 and clinical follow-up, for up to 3 additional years.The aim of the study is to collect safety and efficacy data of long term treatment effect of Diapep277.Only patients who completed studies 901 or 910 and still have stimulated C-peptide level equal to or above 0.2 nmol/L will be eligible for this extension study

Start Date01 Jan 2012

Sponsor / Collaborator

Rabin Medical Center

100 Clinical Results associated with DiaPep-277

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100 Translational Medicine associated with DiaPep-277

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100 Patents (Medical) associated with DiaPep-277

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35

Literatures (Medical) associated with DiaPep-277

01 Dec 2016·EndocrineQ3 · MEDICINE

Antigen-based immunotherapies do not prevent progression of recent-onset autoimmune diabetes: a systematic review and meta-analysis

Q3 · MEDICINE

Review

Author: Rika, Maria ; Rizava, Chrysoula ; Haidich, Anna Bettina ; Galli-Tsinopoulou, Asimina ; Sarigianni, Maria ; Liakos, Aris ; Tsapas, Apostolos ; Bekiari, Eleni

We performed a systematic review and meta-analysis to assess the efficacy and safety of antigen-based immunotherapies in tertiary prevention of autoimmune diabetes. We searched for randomised controlled trials testing antigen-based immunotherapies in patients with recent-onset type 1 diabetes or latent autoimmune diabetes of adults in MEDLINE, COCHRANE and EMBASE databases, trial registries, conference proceedings and reference lists of pertinent records. Primary outcomes were fasting and stimulated C-peptide (after glucagon or mixed meal stimulation). Change in glycosylated haemoglobin (HbA_1c), daily insulin needs and incidence of any or severe hypoglycaemic events or severe adverse events were secondary outcomes. Fifteen studies were included in the meta-analysis. Overall, there was no difference in fasting [weighted mean difference (WMD) 0.01 nmol/L; 95 % confidence interval (CI) -0.09, 0.11; I ² = 73 %] or mixed meal stimulated C-peptide (WMD 0.02 nmol/L/min; 95 % CI -0.08, 0.12; I ² = 50 %) compared with placebo. Glucagon stimulated C-peptide was maintained higher (WMD 0.13 nmol/L/min; 95 % CI 0.05, 0.21; I ² = 0 %) in patients treated with Diapep277. Moreover, there was no change in daily insulin needs (WMD 0.02 IU/kg; 95 % CI -0.04, 0.09; I ² = 51 %) or HbA_1c (WMD -0.06 %; 95 % CI -0.35, 0.23; I ² = 42 %) vs. placebo. Finally, there was no effect on the incidence of severe hypoglycaemic events or overall serious adverse events [risk ratio 0.94, 95 % CI 0.62, 1.41; I ² = 0 % and 0.87; 95 % CI 0.53, 1.44; I ² = 0 %, respectively). Antigen-based immunotherapies are not effective in preventing the progression of autoimmune diabetes in newly diagnosed patients.

20 Oct 2015·Oncotarget

HSP60 - a double edge sword in autoimmunity

Author: Landstein, Dorit ; Ulmansky, Rina ; Naparstek, Yaakov

Human autoimmune inflammatory diseases are usually characterized by a chronic course. Antigen-induced experimental animal models for these diseases, on the other hand, typically present an acute or sub-acute course and after spontaneous recovery the animal may become resistant to reinduction of the disease. One explanation for this course of events may be that the antigen that induces the disease has a dual effect; on one hand it may serve as the target for the pathogenic immune attack whereas on the other it may lead to the development of protective immune mechanisms. Deficiency in these protective immune pathways may lead to the development of chronic autoimmune diseases. In the editorial below we will address this phenomenon by describing an example of one such antigen, HSP60 that has been shown to have a dual role in immune-mediated disorders, being involved in the induction and propagation of autoimmune diseases as well as in suppressing them [1]. HSP60 is a highly conserved protein, which was initially characterized as a mitochondrial chaperone. Upon exposure to stress or immune activation, HSP60 is also found in the cytosol, cell surface, extracellular space and biological fluids. HSP60 activates innate and adaptive immune responses, and can function as an endogenous danger signal to the immune system. It binds to cell surface receptors, including CD14 and members of the TLR family [reviewed by 1]. Overexpression of HSP60 has been described in tissues of various inflammatory diseases suggesting a possible pathogenic role of this antigen in their pathogenesis. Increased expression of human HSP60 is observed in intestinal ulcer of Behcet's Disease (BD) [2], in inflamed bowel of Crohn's disease patients, in muscle tissue of juvenile dermatomyositis (JDM) patients, and in synovial fluid and synovial tissue of juvenile idiopathic arthritis (JIA) and Rheumatoid arthritis (RA) patients [3]. HSP60 is also overexpressed in inflamed lesions of atopic dermatitis where it is co-localized with CD3 positive cells [4]. Peripheral mononuclear cells (PBMCs) taken from patients with various inflammatory diseases can be activated by HSP60. For instance, HSP60 induces IFNγ secretion from atopic dermatitis patients' PBMCs [4] and PBMCs of patients with BD, stimulated with various epitopes of HSP60, resulted in excess amounts of Th1 cytokine production [2]. Several supporting evidence for the pathogenicity of HSP60 have also been reported in experimental animal models of inflammatory diseases. HSP60 is upregulated in animal model of glomerulonephritis (NTN) as shown by increased HSP60 secretion in the urine and into the extracellular space of the diseased kidney. In addition, administration of HSP60 aggravates the disease in the NTN model and in experimental autoimmune uveitis in mice [5, 6]. Contrary to its role as a target for pathogenic autoimmune inflammatory processes, HSP60 has been shown to activate immunoregulatory pathways that may lead to suppression of these diseases. The finding that immunization with whole MT HSP60 prior to induction of adjuvant arthritis (AA) leads to protection against the disease attributed many experiments aimed at revealing the mechanism of this phenomenon, using mammalian and MT whole protein or synthetic peptides of the proteins. HSP60 based treatment ameliorated or suppressed several animal models of inflammatory diseases such as AA, collagen induced arthritis, insulin-dependent diabetes mellitus and atherosclerosis. Preventive as well as therapeutic HSP60 peptide treatment included various regimens, modes of administration and adjuvants and resulted in suppression of inflammatory cytokines, elevation of Th2 cytokines, and induction of regulatory T cells (CD4+CD25+Foxp3+) [3]. Interestingly, the presence of antibodies against peptide 6, a specific peptide derived from MT-HSP60, generated resistance to the induction of AA. We have recently shown that Prozumab, a humanized mAb targeting HSP60, is effective in ameliorating animal models of autoimmune inflammatory diseases such as RA and IBD. In vitro studies performed on human PBMCs were also indicative of an anti-inflammatory effect of Prozumab: Treatment of naive PBMCs resulted in suppression of anti CD3-induced INFγ and IL-6 secretion [7]. Immune reactivity against HSP60 has been found to have a disease suppressing effect in human autoimmune inflammatory diseases as well. The presence of self-HSP60-specific T cell responses in JIA patients correlates with a benign disease course. Self-HSP-specific T cell responses have also been reported to be immunoregulatory in various other autoimmune diseases, such as RA and JDM, by the production of anti-inflammatory cytokines such as interleukin (IL)-10, IL-4 and TGF-β [3]. A phase 2 clinical trial testing the effect of Diapep277 (a human HSP60 derived peptide) in type 1 diabetes, has shown promising results. A phase 3 trial is currently ongoing [1, 3]. In summary HSP60 has been identified as a target for both pathogenic as well as protective immune mechanisms in many experimental and human inflammatory diseases. The upregulation of this protein at the sites of inflammation on one hand and its ability to skew the immune system towards suppression of disease on the other hand may explain the spontaneous remission of many experimental models of these inflammatory diseases. Understanding the putative mechanisms of disease suppression in animal models may lead to novel immunotherapeutic approaches to human autoimmune inflammatory diseases.

01 Jan 2015·Diabetes Care

Evaluation of Long-Term Treatment Effect in a Type 1 Diabetes Intervention Trial: Differences After Stimulation With Glucagon or a Mixed Meal. Diabetes Care 2014;37:1384–1391. DOI: 10.2337/dc13-1392

Author: Avron, Ann ; Peled, Dana ; Raz, Itamar ; Cohen, Irun R. ; Eren, Rachel ; Dagan, Shlomo ; Pozzilli, Paolo ; Elias, Dana ; Tamir, Merana

On behalf of the authors identified below, the corresponding author has formally requested to retract the above-cited article. An accompanying article (1) has also been retracted. The study described in this article uses data from the DIA-AID 1 trial on DiaPep277 to compare treatment effects in patients with type 1 diabetes. The DIA-AID 1 trial, as noted in the Duality of Interest section, was funded by Andromeda Biotech, Ltd. On 8 September 2014, Hyperion Therapeutics, Inc., which acquired Andromeda Biotech in June 2014, announced that it had chosen to terminate the …

2

News (Medical) associated with DiaPep-277

24 Feb 2014

·www.biospace.com

Andromeda Biotech Acquires DiaPep277 Rights From Teva Pharmaceutical Industries Limited

YAVNE, Israel, Feb. 24, 2014 (GLOBE NEWSWIRE) -- Andromeda Biotech Ltd. announces that it entered into an agreement with Teva Pharmaceutical Industries Ltd. for the acquisition of Teva's rights for Andromeda's drug, DiaPep277®, for the treatment of Type 1 Diabetes. Help employers find you! Check out all the jobs and post your resume.

CollaborateAcquisition

12 Sep 2012

·www.biospace.com

Andromeda Biotech Successfully Completes Patient Recruitment in Phase III Confirmatory Trial for Its Lead Drug, "DiaPep277" for Type 1 Diabetes

YAVNE, Israel, Sept. 12, 2012 (GLOBE NEWSWIRE) -- Andromeda Biotech Ltd. ( ) announced today that it has completed patient recruitment in its' DIA-AID 2, a confirmatory Phase III clinical trial using DiaPep277® for the treatment of Type 1 diabetes.

100 Deals associated with DiaPep-277

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetes Mellitus, Type 1	Phase 3	-	Weizmann Institute of Science	-
Diabetes Mellitus, Type 1	Phase 3	-	Weizmann Institute of Science	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00615264 (DIA-AID 1 \| DIA-AID, CTgov)	Phase 3	Diabetes Mellitus, Type 1	457	DiaPep277 (DiaPep277)	cqljmdjaxu(spwdzuimqy) = vqtyoqmgez rueoulcqps (eppgbkxfsm, htdfaxebjq - bjakrcvmzh) View more	-	06 Jun 2016
				Placebo (Placebo)	cqljmdjaxu(spwdzuimqy) = xgvztdjbag rueoulcqps (eppgbkxfsm, ppeawtmqkt - rzftrokopx) View more
NCT01898286 (DIA-AID 2, CTgov)	Phase 3	Diabetes Mellitus, Type 1	38	DiaPep	fyrdmjtrvi(fvxygcudzf) = izilgbiruy kpwkkmnnzv (ykaxtjanhn, ibukzhzqlq - yxmvuyldmo) View more	-	26 May 2016
NCT01103284 (DIA-AID2, CTgov)	Phase 3	Diabetes Mellitus, Type 1	475	DiaPep277 (DiaPep277)	holatgdhcp(rvmfwyxscv) = lnhqjfoqes fmyknuhaxr (jbbrdblfgd, rjickxtbue - jqsacteahn) View more	-	26 May 2016
				Placebo (Placebo)	holatgdhcp(rvmfwyxscv) = kogpmkdmuf fmyknuhaxr (jbbrdblfgd, lgjuviewmn - ipamdunjqr) View more
DIA-AID 1 (EASD2013)	Phase 3	stimulated C-peptide levels	43	DiaPep277®	(hbygwrnafv) = Out of 81 adverse events reported by 31 subjects, only two were related to the study drug, both of which were resolved. Only one severe adverse event was reported which was not considered related to the study medication. The most common non-related adverse events were infections and infestations (35/81, 43%) followed by gastrointestinal disorders (9/81, 11%) cqpctsdgux (stwqkovreo )	Positive	25 Sep 2013
				Placebo
NCT00615264 (DIA-AID 1, EASD2012)	Phase 3	Diabetes Mellitus, Type 1 C-peptide \| islet autoantibodies	457	DiaPep277	gemifrjnmu(wxhhbagnbg) = bsqvdfwvpo iggkyyulrd (roqvpfadug ) View more	Positive	04 Oct 2012
				Placebo	gemifrjnmu(wxhhbagnbg) = fytmcxnckk iggkyyulrd (roqvpfadug ) View more