Delving into the Latest Updates on REP-2139 with Synapse

Overview

Basic Info

Drug Type

Oligonucleotide

Synonyms

REP 2139 magnesium chelate, REP 2139, REP 2139 calcium chelate

+ [6]

Target

HBsAg

Mechanism

HBsAg inhibitors(HBsAg inhibitors)

Therapeutic Areas

Infectious DiseasesDigestive System DisordersOther Diseases

Active Indication-

Inactive Indication

Hepatitis BHepatitis B, ChronicHepatitis D

Originator Organization

Replicor, Inc.

Active Organization-

Inactive Organization

Replicor, Inc.

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure

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Gene Sequence

Sequence Code 29538155

NAPs have been previously shown to clear serum hepatitis B virus surface antigen (HBsAg) both preclinically (in duck HBV infected ducks) and in human patients. REP 2139-Ca mediated HBsAg clearance acts synergistically with immunotherapeutic agent pegylated interferon-alpha 2a to restore host immunological control of HBV infection. REP 2165 is a version of REP 2139 which has been shown preclinically to retain antiviral activity with lower accumulation in the liver.
Both REP 2139 and REP 2165 used in this protocol are formulated as magnesium chelate complexes, which improve their administration tolerability. This open label, randomized and controlled study will examine the safety and efficacy of REP 2139-Mg and REP 2165-Mg therapy in patients with HBeAg negative chronic hepatitis B when used in combination with tenofovir disoproxil fumarate and pegylated interferon alpha-2a.

Start Date01 Mar 2016

Sponsor / Collaborator

Replicor, Inc.

NCT02233075 / CompletedPhase 2

A Study of the Safety and Efficacy of Combination Treatment With REP 2139-Ca and Pegasys™ in Patients With Hepatitis B / Hepatitis D Co-infection

REP 2139-Ca is nucleic acid polymer. Nucleic acid polymers have been previously shown to clear serum hepatitis B virus surface antigen (HBsAg) both preclinically (in duck HBV infected ducks) and in human patients and to act synergistically with immunotherapeutic agents such as pegylated interferon-alpha 2a or thymosin alpha-1 to restore host immunological control of HBV infection.
HBsAg is an essential component of the hepatitis D virus (HDV), therefore the direct action of REP 2139-Ca in removing serum HBsAg and its synergistic effect with pegylated interferon-alpha 2a is expected to have a significant antiviral effect against HDV infection.
This study will examine the safety and efficacy of REP 2139-Ca therapy when used in combination with pegylated interferon alpha-2a in patients with HBV / HDV co-infection.
The primary hypothesis to be tested is that this combined dosing regimen is safe and well tolerated in patients with HBV / HDV co-infection which will be assessed by examining the number of patients with adverse events (including reported symptoms and laboratory abnormalities).
The secondary hypothesis to be tested is that this combined dosing regimen will have an antiviral effect against HBV / HDV co-infection in these patients which will be assessed by examining the following outcomes:
The number of patients with reductions in serum HBsAg.
The number of patients with reductions in serum HDAg and HDV RNA
The number of patients that experience a sustained antiviral response after treatment is stopped (reductions in serum HBV DNA and HDV RNA).
The secondary hypothesis to be tested is that this combination approach can have an effective

Start Date01 Sep 2014

Sponsor / Collaborator

Replicor, Inc.

NCT02726789 / CompletedPhase 2

Therapeutic Safety and Efficacy of Combination Treatment With REP 2139-Ca and Pegasys in Patients With Chronic Hepatitis B

The REP 201 protocol is a small exploratory study assessing the antiviral effects and tolerability of REP 2139-Ca when used with a full course of pegylated interferon (48 weeks) in treatment naive patients or in patients already receiving entecavir and continuing entecavir with treatment.

Start Date01 Oct 2012

Sponsor / Collaborator

Replicor, Inc.

100 Clinical Results associated with REP-2139

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100 Translational Medicine associated with REP-2139

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100 Patents (Medical) associated with REP-2139

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34

Literatures (Medical) associated with REP-2139

01 Apr 2024·Antiviral research

An in vivo duck hepatitis B virus model recapitulates key aspects of nucleic acid polymer treatment outcomes in chronic hepatitis B patients

Article

Author: Hong, Jin ; Chanda, Sushmita ; Ebwanga, Ebanja Joseph ; Raboisson, Pierre ; Beigelman, Leonid ; Kum, Dieudonné Buh ; Thatikonda, Santhosh Kumar ; Acosta Sanchez, Abel ; Debing, Yannick ; Rajwanshi, Vivek ; Kariuki, Christopher Kinyanjui ; Merckx, Wouter ; Silva de Oliveira, Daniel Apolônio ; Symons, Julian A ; Gohil, Vikrant ; Lin, Tse-I ; Vanrusselt, Hannah ; Smith, David B ; Blatt, Lawrence M ; Bashir, Shahbaz ; Paeshuyse, Jan ; Jekle, Andreas ; Degrauwe, Lars

Nucleic acid polymers (NAPs) are an attractive treatment modality for chronic hepatitis B (CHB), with REP2139 and REP2165 having shown efficacy in CHB patients. A subset of patients achieve functional cure, whereas the others exhibit a moderate response or are non-responders. NAP efficacy has been difficult to recapitulate in animal models, with the duck hepatitis B virus (DHBV) model showing some promise but remaining underexplored for NAP efficacy testing. Here we report on an optimized in vivo DHBV duck model and explore several characteristics of NAP treatment. REP2139 was efficacious in reducing DHBV DNA and DHBsAg levels in approximately half of the treated ducks, whether administered intraperitoneally or subcutaneously. Intrahepatic or serum NAP concentrations did not correlate with efficacy, nor did the appearance of anti-DHBsAg antibodies. Furthermore, NAP efficacy was only observed in experimentally infected ducks, not in endogenously infected ducks (vertical transmission). REP2139 add-on to entecavir treatment induced a deeper and more sustained virological response compared to entecavir monotherapy. Destabilized REP2165 showed a different activity profile with a more homogenous antiviral response followed by a faster rebound. In conclusion, subcutaneous administration of NAPs in the DHBV duck model provides a useful tool for in vivo evaluation of NAPs. It recapitulates many aspects of this class of compound's efficacy in CHB patients, most notably the clear division between responders and non-responders.

28 Sep 2023·Current issues in molecular biology

Interferon-Free Regimens and Direct-Acting Antiviral Agents for Delta Hepatitis: Are We There Yet?

Review

Author: Hincu, Corina Elena ; Ciortescu, Irina ; Plesa, Alina ; Gheorghe, Liliana ; Nemteanu, Roxana ; Clim, Andreea

Chronic delta hepatitis is a global health problem. Although a smaller percentage of chronic HBV-infected patients are coinfected with the hepatitis delta virus, these patients have a higher risk of an accelerated progression to fulminant "delta hepatitis", cirrhosis, hepatic decompensation, and hepatocellular carcinoma, putting a financial strain on the healthcare system and increasing the need for a liver transplant. Since its discovery, tremendous efforts have been directed toward understanding the intricate pathogenic mechanisms, discovering the complex viral replication process, the essential replicative intermediates, and cell division-mediated viral spread, which enables virion viability. The consideration of the interaction between HBV and HDV is crucial in the process of developing novel pharmaceuticals. Until just recently, interferon-based therapy was the only treatment available worldwide. This review aims to present the recent advancements in understanding the life cycle of HDV, which have consequently facilitated the development of innovative drug classes. Additionally, we will examine the antiviral strategies currently in phases II and III of development, including bulevirtide (an entry inhibitor), lonafarnib (a prenylation inhibitor), and REP 2139 (an HBsAg release inhibitor).

01 Sep 2021·GutQ1 · MEDICINE

Hepatitis D virus in 2021: virology, immunology and new treatment approaches for a difficult-to-treat disease

Q1 · MEDICINE

Review

Author: Lampertico, Pietro ; Neumann-Haefelin, Christoph ; Urban, Stephan

Approximately 5% of individuals infected with hepatitis B virus (HBV) are coinfected with hepatitis D virus (HDV). Chronic HBV/HDV coinfection is associated with an unfavourable outcome, with many patients developing liver cirrhosis, liver failure and eventually hepatocellular carcinoma within 5–10 years. The identification of the HBV/HDV receptor and the development of novel in vitro and animal infection models allowed a more detailed study of the HDV life cycle in recent years, facilitating the development of specific antiviral drugs. The characterisation of HDV-specific CD4+ and CD8+T cell epitopes in untreated and treated patients also permitted a more precise understanding of HDV immunobiology and possibly paves the way for immunotherapeutic strategies to support upcoming specific therapies targeting viral or host factors. Pegylated interferon-α has been used for treating HDV patients for the last 30 years with only limited sustained responses. Here we describe novel treatment options with regard to their mode of action and their clinical effectiveness. Of those, the entry-inhibitor bulevirtide (formerly known as myrcludex B) received conditional marketing authorisation in the European Union (EU) in 2020 (Hepcludex). One additional drug, the prenylation inhibitor lonafarnib, is currently under investigation in phase III clinical trials. Other treatment strategies aim at targeting hepatitis B surface antigen, including the nucleic acid polymer REP2139Ca. These recent advances in HDV virology, immunology and treatment are important steps to make HDV a less difficult-to-treat virus and will be discussed.

100 Deals associated with REP-2139

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hepatitis B	Phase 2	MD	Replicor, Inc.	01 Sep 2014
Hepatitis D	Phase 2	MD	Replicor, Inc.	01 Sep 2014
Hepatitis B, Chronic	Phase 2	-	Replicor, Inc.	01 Oct 2012

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05683548 (RCAP, DDW2024)	Not Applicable	Hepatitis B \| Hepatitis D \| Liver Diseases quantitative HBsAg \| anti-HBs \| HBV DNA ... View more	31	REP 2139-Mg	vorjumvkuq(qkvlxcpewc) = iyuirqgpnd ylwxmpimps (qoudwribpf )	Positive	18 May 2024
NCT05683548 (RCAP, DDW2024)	Not Applicable	Hepatitis B \| Hepatitis D \| Liver Diseases quantitative HBsAg \| anti-HBs \| HBV DNA ... View more	31	REP 2139-Mg 250mg qW SC	mvscznwsjv(kmccfnxdoc) = wvuxohjppf wgnahwmhlg (chqensjcza ) View more	Positive	18 May 2024
DDW2024	Not Applicable	Hepatitis B \| Hepatitis D \| Liver Diseases	-	REP 2139-Mg 250mg qW SC	ibopztapds(eiawsvzyly) = hkqojuxiza eanbipnvij (ctezlhrgoq ) View more	-	18 May 2024
NCT05683548 (RCAP, DDW2024)	Not Applicable	Hepatitis B \| Hepatitis D \| Liver Diseases quantitative HBsAg \| anti-HBs \| HBV DNA ... View more	31	REP 2139-Mg 250mg qW SC	jzfncpxjxn(hensrucnch) = ysbeeouymz tesjnaeagw (nkqlkuhfmx )	Positive	18 May 2024
AASLD2023	Not Applicable	Decompensated cirrhosis of liver	3	REP 2139-Mg 250 mg	cynakdnenz(qcilcmkrjq) = No significant adverse events (including ALT elevation) have been observed to date zwotcsjthe (ocjejtkund )	-	10 Nov 2023
DDW2023	Not Applicable	Hepatitis B \| Hepatitis D \| Liver Cirrhosis	-	REP 2139-Mg 250mg	spnncwwhfx(xkppfpstdd) = Central obesity likely prevents optimal liver accumulation of REP 2139 in one patient brozybwtar (wrwtxnccxt ) View more	-	08 May 2023
NCT02565719 (Pubmed) Manual	Phase 2	Hepatitis B	40	TDF + pegIFN + REP 2139-Mg or REP 2165-Mg (NAP groups)	suogzebniw(yynbcydknx) = PegIFN-induced thrombocytopenia (P = .299 vs controls) and neutropenia (P = .112 vs controls) were unaffected by NAPs (REP 2139 vs REP 2165). Increases in levels of transaminases were significantly more frequent (P < .001 vs controls) and greater (P = .002 vs controls) in the NAP groups (but did not produce symptoms), correlated with initial decrease in HBsAg, and normalized during therapy and follow-up. rjuqcogetx (vfofolaawm ) View more	Positive	06 Mar 2020
NCT02565719 (Pubmed) Manual	Phase 2	Hepatitis B	40	TDF + pegIFN		Positive	06 Mar 2020
NCT02646189 (REP 102, Pubmed \| J Viral Hepat)	Phase 1/2	-	12	REP 2139-Ca	ejsokgrnhy(vkaauxdzpu) = geevgyrvdt yoynpqwdat (upxuokbuou ) View more	-	01 Dec 2019
NCT02726789 (CTgov)	Phase 2	Hepatitis B, Chronic	5	REP 2139-Ca+Entecavir+pegylated interferon	obolacmuzf(cgabbdfuwm) = nwyowteedn tecjlyltjb (qcxycxngow, kazbglsxdw - mjifvqzqxc) View more	-	08 May 2019
NCT02233075 (REP 301, Pubmed \| Lancet Gastroenterol Hepatol) Manual	Phase 2	Hepatitis B, Chronic \| Hepatitis D First line	12	REP 2139+pegylated interferon alfa-2a	rqixniwfea(trvudpuynr) = dbzymehkvs wmpxzyhlcc (apmtagbilm ) View more	Positive	28 Sep 2017