FRI-210-Establishment of high rates of functional cure of HBeAg negative chronic HBV infection with REP 2139-Mg based combination therapy: Ongoing follow-up results from the REP 401 study

Bazinet, Michel; Pântea, Victor; Plăcintă, Gheorghe; Moscalu, Iurie; Cebotarescu, Valentin; Cojuhari, Lilia; Jimbei, Pavlina; Iarovoi, Liviu; Smeşnoi, Valentina; Musteata, Tatiana; Jucov, Alina; Krawczyk, Adalbert; Vaillant, Andrew

doi:10.1016/s0618-8278(19)30955-7

Cited by 6 publications

(15 citation statements)

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“…Efficacy of REP‐2139 was studied in patients from Bangladesh and Moldova . Promising results in regard to HBsAg reduction and HBsAg loss are presented with mono and combination therapy of REP‐2139.…”

Section: Drug Targetsmentioning

confidence: 62%

“…Interim data from a larger trial (study 401), that included a TDF lead‐in phase of 24 weeks followed by 48 weeks of treatment with REP‐2139 combined with TDF and peg‐IFN‐α, found that 24/40 patients had HBsAg seroconversion to anti‐HBs by the end of treatment. This effect appeared sustained off drugs, 20/34 and 9/16 still had HBsAg loss and positive anti‐HBs at follow‐up weeks 24 and 48, respectively …”

Section: Drug Targetsmentioning

confidence: 99%

“…During treatment, reduction in platelet counts and ALT/AST flares were frequently (33%‐68%) reported during monotherapy but mostly after initiation of peg‐IFN‐α. These flares were mostly self‐resolving.…”

Section: Drug Targetsmentioning

confidence: 99%

“…These flares were mostly self‐resolving. The researchers suggest that these ALT/AST flares are a result of peg‐IFN‐α treatment restoring immunity against infection . This fits the hypothesis of reducing HBsAg load, providing an opportunity for controlling the infection with the help of immune therapy (peg‐IFN‐α).…”

Section: Drug Targetsmentioning

confidence: 99%

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Review article: clinical pharmacology of current and investigational hepatitis B virus therapies

Smolders

Burger

Feld

et al. 2019

Aliment Pharmacol Ther

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Summary Background Treatment of hepatitis B virus (HBV) infection with current therapy suppresses HBV DNA, but loss of hepatitis B surface antigen (HBsAg; functional cure), is rare. Multiple compounds are under investigation. Aims To describe the pharmacology, including drug interactions, efficacy, safety and mechanisms of action of investigational compounds for HBV infection. Methods Descriptive review using PubMed and Google to identify literature/conference papers on investigational compounds (≥Phase 2) with data on efficacy and safety in HBV‐infected patients. Results Bulevirtide, JNJ‐56136379, ABI‐H0731, REP‐2139, and inarigivir decrease HBV DNA/RNA, with greater potency than current nucleos(t)ide analogues. REP‐2139 (25%‐75% of patients, 20‐48 weeks treatment) and inarigivir (26% of patients, 12‐24 weeks treatment) induce HBsAg loss. ARO‐HBV reduced (>1.5 log10 UI/mL) HBsAg in 85% of patients (12 weeks treatment). There are some safety concerns with investigational agents (e.g., increased bile acids with bulevirtide, and liver enzyme flares with REP‐2139) which will require a risk benefit assessment compared with current therapies. Single and multidose pharmacokinetic data are available for bulevirtide, JNJ‐56136379, ABI‐H0731; no such data are available for REP‐2139, ARO‐HBV, inarigivir. Initial drug interaction assessments have been performed with bulevirtide and inarigivir (only in vitro). Conclusions There are promising investigational therapies for HBV infection. Increasing the potential for HBsAg loss may result in more patients achieving functional cure. However, many knowledge gaps remain such as pharmacokinetics in those with HBV, cirrhosis and renal impairment but also the interaction potential between investigational therapies, risk‐benefit profiles, and potential for drug interactions with medications used to treat comorbidities associated with aging.

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Section: Drug Targetsmentioning

confidence: 62%

Section: Drug Targetsmentioning

confidence: 99%

Section: Drug Targetsmentioning

confidence: 99%

Section: Drug Targetsmentioning

confidence: 99%

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Review article: clinical pharmacology of current and investigational hepatitis B virus therapies

Smolders

Burger

Feld

et al. 2019

Aliment Pharmacol Ther

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“…NAPs can block HBV during and after viral entry, providing a novel NAPs‐specific post‐entry activity in HBV. Small proof‐of‐concept clinical trials in HBeAg‐negative patients have suggested that the add‐on of NAPs in NAs+pegIFNa2a therapy blocks HBsAg release from infected cells leading to a functional cure in 39% of patients . However, more research is needed to understand this post‐entry mechanism and the ALT flares experienced by most patients.…”

Section: Introductionmentioning

confidence: 99%

Can we cure hepatitis B virus with novel direct‐acting antivirals?

Martínez

Villeret

Testoni

et al. 2020

Liver International

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Current treatments against chronic hepatitis B (CHB) include pegylated interferon alpha (Peg‐IFNα) and nucleos(t)ide analogs (NAs), the latter targeting the viral retrotranscriptase, thus inhibiting de novo viral production. Although these therapies control infection and improve the patient's quality of life, they do not cure HBV‐infected hepatocytes. A complete HBV cure is currently not possible because of the presence of the stable DNA intermediate covalently closed circular DNA (cccDNA). Current efforts are focused on achieving a functional cure, defined by the loss of Hepatitis B surface antigen (HBsAg) and undetectable HBV DNA levels in serum, and on exploring novel targets and molecules that are in the pipeline for early clinical trials. The likelihood of achieving a long‐lasting functional cure, with no rebound after therapy cessation, is higher using combination therapies targeting different steps in the hepatitis B virus (HBV) replication cycle. Novel treatments and their combinations are discussed for their potential to cure HBV infection, as well as exciting new technologies that could directly target cccDNA and cure without killing the infected cells.

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Pathogenetic Mechanisms of T Cell Dysfunction in Chronic HBV Infection and Related Therapeutic Approaches

et al. 2020

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FRI-210-Establishment of high rates of functional cure of HBeAg negative chronic HBV infection with REP 2139-Mg based combination therapy: Ongoing follow-up results from the REP 401 study

Cited by 6 publications

References 0 publications

Review article: clinical pharmacology of current and investigational hepatitis B virus therapies

Review article: clinical pharmacology of current and investigational hepatitis B virus therapies

Can we cure hepatitis B virus with novel direct‐acting antivirals?

Pathogenetic Mechanisms of T Cell Dysfunction in Chronic HBV Infection and Related Therapeutic Approaches

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