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

Action

inhibitors

Mechanism

HBsAg inhibitors(HBsAg inhibitors)

Therapeutic Areas

Infectious DiseasesDigestive System Disorders

Active Indication

Hepatitis B

Inactive Indication

Hepatitis B, ChronicHepatitis D

Originator Organization

Replicor, Inc.

Active Organization

Replicor, Inc.

Inactive Organization-

License Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure/Sequence

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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:
1. The number of patients with reductions in serum HBsAg.
2. The number of patients with reductions in serum HDAg and HDV RNA
3. 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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35

Literatures (Medical) associated with REP-2139

01 Nov 2025·JOURNAL OF HEPATOLOGY

Safety and efficacy of REP 2139-Mg in patients with HDV-related advanced liver disease in an international compassionate access program

Article

Author: Douglas, Mark ; Ben-Ali, Souad ; Dahari, Harel ; Francois, Sandrine ; Jachs, Mathias ; Yurdaydin, Cihan ; Vitale, Alessandro ; Gerber, Athenaïs ; Metivier, Sophie ; Schramko, Jocelyn ; Baril, Marie-Éve ; Brancaccio, Giuseppina ; Brichler, Ségolène ; Testoni, Barbara ; Levrero, Massimo ; Svicher, Valentina ; Loustaud-Ratti, Véronique ; Bourliere, Marc ; Lecomte, Laurence ; Etzion, Ohad ; Chevaliez, Stéphane ; Kaysin, Furkan ; Mackiewicz, Vincent ; Colombain, Lea ; Bedoya, Jose Ursic ; Metin, R Olga ; Morvan, Christopher ; Zoulim, Fabien ; Gaeta, Giovanni Battista ; Reiberger, Thomas ; de Freitas, Cecilia ; Yardeni, David ; Mathurin, Philippe ; Schwarz, Michael ; Bondezi, Kindness ; Meszaros, Magdalena ; Stern, Christiane ; Paradis, Valerie ; Bazinet, Michel ; Vaillant, Andrew ; Bardou-Jacquet, Edouard ; Poulin, Sébastien ; Alric, Laurent ; Plissonnier, Marie-Laure ; Neumann-Haefelin, Christoph ; Gordien, Emmanuel

BACKGROUND & AIMS:

REP 2139-Mg (REP), a nucleic acid polymer, blocks HBV subviral particle assembly and HDV replication. We report the outcomes of REP treatment in patients with HDV enrolled in a compassionate access program (NCT05683548).

METHODS:

Thirty-three patients with HDV and advanced chronic liver disease received weekly subcutaneous REP 250 mg plus a nucleotide analogue for a planned 48-week treatment course. Pegylated interferon-α (PegIFN) 45-180 μg weekly was added in 20 patients without contraindications. Safety and efficacy were assessed regularly, and intrahepatic markers were evaluated in one liver explant.

RESULTS:

Among the 33 patients (age 21-69 years; 21 males), 85% (28/33) had prior treatment failure, and six had decompensated cirrhosis (ascites in five). Suboptimal responses to REP were managed with dose modifications (250 mg intravenously or 500 mg subcutaneously or intravenously) and/or treatment extension in 21 patients. At end of therapy, HDV RNA declined by >2 log₁₀ in 70% (23/33) and became undetectable in 58% (19/33). HBsAg loss occurred in 27% (9/33). Among the 28 patients with available follow-up, HDV RNA and HBsAg remained undetectable in 46% (13/28) and 18% (5/28), respectively. ALT normalized in 50% (14/28). Responses were similar with or without PegIFN. Ascites improved in two of five affected patients. Three patients underwent liver transplantation while receiving REP without complications. In one liver explant, HDV RNA and HDAg were undetectable, and intrahepatic covalently closed circular DNA activity and HBsAg levels were very low. No REP-related serious adverse events were observed.

CONCLUSIONS:

REP treatment was safe and effective in patients with HDV and advanced chronic liver disease. REP may induce sustained virological response of HDV and functional cure of HBV, independent of PegIFN co-administration. Clinical improvement may also occur in patients with decompensated cirrhosis.

IMPACT AND IMPLICATIONS:

No approved antiviral therapy exists for patients with chronic hepatitis D (CHD) and decompensated cirrhosis, or for those who have failed bulevirtide and/or pegylated interferon. In the Replicor Compassionate Access Program, 33 patients with CHD and advanced chronic liver disease received REP 2139-Mg (REP) plus a nucleotide analogue, with or without pegylated interferon. HBsAg loss occurred in 27% at end of treatment and remained undetectable in 18% after 1 year, indicating sustained HDV virological response and HBV functional cure. Among six patients with decompensated cirrhosis, five achieved a virological response and two showed clinical improvement with reduced ascites. No REP-related serious adverse events were observed. Overall, REP demonstrated promising efficacy and acceptable tolerability in this difficult-to-treat population and warrants evaluation in a response-guided clinical trial.

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 ; Thatikonda, Santhosh Kumar ; Kum, Dieudonné Buh ; Acosta Sanchez, Abel ; Debing, Yannick ; Rajwanshi, Vivek ; Kariuki, Christopher Kinyanjui ; Merckx, Wouter ; Silva de Oliveira, Daniel Apolônio ; Symons, Julian A ; Gohil, Vikrant ; Vanrusselt, Hannah ; Lin, Tse-I ; 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.

01 Jun 2023·Hepatology (Baltimore, Md.)

Clinical trials in hepatitis D virus: Measuring success

Article

Author: Da, Ben L

Chronic hepatitis D infection results in the most severe form of chronic viral hepatitis but currently lacks effective treatment options. Therapy with pegylated interferon alpha is recommended for finite treatment duration by major liver societies. Still, it is plagued by low rates of sustained virologic response (SVR) and frequent relapses even if SVR is achieved. Recently, a wave of investigational therapies has come under evaluation, including bulevirtide, lonafarnib, pegylated interferon lambda, and REP‐2139 creating excitement with this viral infection. However, there has been significant variability in the endpoints used to evaluate these therapeutics. One of the recently introduced endpoints is characterized by a decline in HDV RNA by 2 logs, with or without achieving an undetectable serum hepatitis D virus (HDV) RNA, as a marker of virologic response. Furthermore, this measure has been combined with alanine aminotransferase normalization, also known as a biochemical response, to formulate the primary endpoint of several late‐stage studies. Per recent guidance by the US Food and Drug Administration, these should be surrogate endpoints that will ultimately portend long‐term clinical benefits. These clinical benefits may include reducing the risk of progression to cirrhosis, hepatic decompensation, hepatocellular carcinoma, liver transplantation, and mortality. However, the optimal way to measure success in HDV clinical trials remains unknown and will continue to evolve.

1

News (Medical) associated with REP-2139

07 Dec 2025

·www.prnewswire.com

Replicor publishes data from its compassionate access program in HBV/HDV

MONTREAL, Dec. 7, 2025 /PRNewswire/ - Replicor Inc. announced the publication of data from its first global compassionate access program in the Journal of Hepatology (see here). This compassionate access program, initiated with Dr. Marc Bourlière in France, deployed REP 2139-Mg in patients with chronic HBV / HDV infection who had failed on bulevirtide or lonafarnib and who had cirrhosis or decompensated cirrhosis. The access program treated 33 patients at 16 different sites in 8 different countries. Important highlights from this paper include Excellent safety of REP 2139-Mg in this fragile patient population. Rapid reversal of symptoms of decompensation and re-compensation. The achievement of high rates of HDV cure and HBV functional cure. The elimination of HBV and HDV from the liver after as little as 10 weeks of therapy. Dr. Andrew Vaillant, CSO of Replicor commented, "REP 2139 is a unique bifunctional agent which directly targets HDV replication and subviral particle assembly. These data continue to reaffirm excellent safety and efficacy of REP 2139-Mg, even in patients with decompensated cirrhosis, and set the stage for phase IIA trials in Europe." About Replicor Replicor is a privately held biopharmaceutical company with the most advanced animal and human clinical data in the development of the cure for HBV and HDV infection. The company is dedicated to accelerating the development of an effective treatment for patients with HBV and HBV/HDV co-infection. For further information about Replicor please visit our website at . SOURCE Replicor Inc. 21% more press release views with Request a Demo

Phase 2

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 D	Phase 2	Moldova	Replicor, Inc.	01 Sep 2014
Hepatitis B	Phase 2	Moldova	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 (Pubmed \| J Hepatol)	Not Applicable	Hepatitis D	33	REP 2139-Mg plus nucleotide analog	otcakvajrt(zcppunuuds) = jjtzmyuyid wzchxvlqcy (hsidqogfvc ) View more	Positive	01 Nov 2025
DDW 12024 \| DDW 22024 \| DDW 32024 \| DDW 42024	Not Applicable	Hepatitis B \| Hepatitis D \| Liver Diseases	-	REP 2139-Mg 250mg qW SC	obpwvqnapj(xrxuwngnmm) = bdvahwnwxn tipicaczrt (xzisnybyle ) View more	-	18 May 2024
NCT02565719 (Pubmed) Manual	Phase 2	Hepatitis B	40	TDF + pegIFN + REP 2139-Mg or REP 2165-Mg (NAP groups)	wbzwewafpd(jyrulqvigc) = 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. fmqmxtwqwn (dxeuzwlvqr ) 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	Hepatitis B	12	REP 2139-Ca	colbfweptx(ieaoewbwth) = cqiphxqmvv ofdosqwimx (lledwwyfvc ) View more	-	01 Dec 2019
NCT02726789 (CTgov)	Phase 2	Hepatitis B, Chronic	5	REP 2139-Ca+pegylated interferon+Entecavir	lgkiiljsbw = zvwxzjwibx mjsjjyivwa (ttldnhdyoq, mvcqbuxeka - pxjauyxdkj) 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	pkqkaczofz(kzcumdckmi) = lmkpjcntif kyzvpvioed (ifwiyklfys ) View more	Positive	28 Sep 2017
NCT02646163 \| NCT02646189 (Pubmed \| PLoS One)	Phase 1/2	Hepatitis B, Chronic	20	REP 2055	ljbxqvoejp(lvlsrdlrct) = erboifrezy kpuxdvwfzl (qreqqygkeu ) View more	-	01 Jan 2016
NCT02646163 \| NCT02646189 (Pubmed \| PLoS One)	Phase 1/2	Hepatitis B, Chronic	20	REP 2139-Ca	ljbxqvoejp(lvlsrdlrct) = retxfljyrc kpuxdvwfzl (qreqqygkeu ) View more	-	01 Jan 2016