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Drug Watch

Drugs in Development for Hepatitis Delta:

Drug

Mechanism

Company

Clinical Trial Phase

Designations

 Lonafarnib + Ritonavir
Prenylation Inhibitor
Eiger BioPharma, USA
Phase III (Fully enrolled - data expected by early 2023)         
 FDA Breakthrough Therapy Designation
 FDA Fast Track Designation
 FDA Orphan Drug Designation
 EMA Orphan Drug Designation
EMA PRIME 
Hepcludex (Formerly Myrcludex B)

 

Entry Inhibitor
Gilead Sciences, Inc.
Monotherapy: Conditional approval by EMA & Biologics License Application filed with FDA - ongoing Phase III trials
 EMA PRIME
 FDA Breakthrough Therapy   Designation
 FDA Orphan Drug Designation
 Promising Innovative Medicine (PIM) Designation by British MHRA
Lambda (Pegylated Interferon)
Immune Response  Stimulator
Eiger BioPharma, USA
Phase III Enrolling
 FDA/EMA Orphan Drug Designation
 FDA Fast Track Designation
 FDA Breakthrough Therapy Designation
JNJ 3989 + Nucleos(t)ide Analog
RNA Interference Compound
Janssen Research & Development, LLC
Phase II Recruiting
N/A
REP 2139 - Mg (in combination with PEG-IFN and Tenofovir)
HBsAg Inhibitor
 Replicor, Canada
Phase II planning in progress (Europe)

 

 N/A
Vir 2218 + Vir 3434
SiRNA Immune Response Stimulator/HBsAg Inhibitor/Entry Inhibitor
Vir Biotechnology
Phase 2
N/A
Ropeginterferon Alfa-2b (P1101)
Immune Respnse Stimulator
PharmaEssentia
Phase 1
N/A
HBV/HDV Entry Inhibitor & Interferon Alpha Receptor Agonist
Entry Inhibitor
Assembly BioSciences
Pre-clinical
N/A
GI-18000
Immune Response  Stimulator
GlobeImmune, USA
Pre-clinical
 N/A
Chart Updated November 2022

Glossary:
 

Terms: HBV = Hepatitis B Virus, CHB = Chronic Hepatitis B, HDV = Hepatitis Delta Virus, CHD = Chronic Hepatitis Delta, PEG-IFN = Pegylated interferon, NTCP = Sodium/Taurocholate Cotransporting Polypeptide, HBsAg = Hepatitis B Surface Antigen, RNA = Ribonucleic Acid, ASPIN = Active Site Polymerase Inhibitor Nucleotide, SiRNA = Small Interfering RNA (a strand of synthetic RNA designed to specifically target a particular messenger RNA for destrutcion), FDA = U.S. Food and Drug Administration, EMA = European Medicines Agency, NIH = National Institutes of Health, British MHRA = Great Britain Medicines and Healthcare products Regulatory Agency


Interferon Alpha (IFN-α)

Pegylated interferon alpha has been used as an off-label treatment for CHD since 1980. Viral response rates typically range between 25 and 30% with this treatment. International guidelines recommend a treatment duration of 48 weeks. A high relapse rate and severe side effects with INF-α make the study of alternative treatments timely and critical.

Lonafarnib + Ritonavir

Lonafarnib is a "prenylation inhibitor" and works by targeting the protein assembly process, which prevents new viruses from being created. Lonafarnib combined with Ritonavir has shown promise in reducing hepatitis delta virus levels. Eiger Biopharmaceuticals has completed enrollment for their Phase III D-LIVR clinical trial and data is expected by early 2023. Lonafarnib has been granted Fast Track Designation and Breakthrough Therapy Designation by the FDA, PRIME Eligibility Designation by the EMA, and Orphan Drug Designation by the FDA and EMA. 

Hepcludex (formerly Myrcludex B)

Hepcludex (generic name bulevirtide) is an “entry inhibitor” that works by stopping the hepatitis delta virus from entering and infecting hepatocytes (liver cells), and breaking the cycle of reinfection. It has shown activity against the hepatitis B virus, and in July 2020 was approved by the European Commission for prescription in Europe, including Russia and the former Soviet Union, as the first effective hepatitis D drug in the world. In September 2020, it was launched in Germany, France, and Austria. In November 2021, Gilead Sciences filed a Biologics License Application with the FDA for approval of the drug in the United States. In November of 2022, this application was not approved, but this was related to concerns about the manufacture and delivery of the drug, rather than its clinical efficacy or safety, so hopes are high that the application will be re-submitted quickly and approved in 2023. Studies have also shown promise for Hepcludex when combined with PEG-IFN in reducing hepatitis delta viral levels. Gilead Sciences, Inc. is still conducting Phase III clinical trials, which are no longer recruiting patients, to investigate the long-term effects of Hepcludex. These studies have shown the achievement of significant response for HDV at 48 weeks. This drug has been granted PRIME Eligibility by the EMA, Breakthrough Therapy and Orphan Drug Designation by the FDA, and Promising Innovative Medicine Designation by the British MHRA.

Pegylated-Interferon-Lambda (PEG-IFN-λ)

Pegylated-Interferon-Lambda is a type III interferon that works by activating the body's own immune system to fight the virus. Research has shown the ability of combination therapy with ritonavir and Lonafarnib to reduce hepatitis delta virus levels and Eiger BioPharmaceuticals is currently enrolling participants in its Phase III LIMT-2 Study. PEG-IFN-λ has been granted Breakthrough Therapy and Fast Track Designation by the FDA, and Orphan Drug Designation by the FDA and EMA.

JNJ-3989 + Nucleos(t)ide Analog

JNJ 3989 is an RNA interference compound that works by targeting transcription of viral RNA, specifically those deriving from HBV cccDNA (this stands for closed covalent circular DNA, a unique DNA structure that forms in response to infection of a cell), which could also impact HDV infection. So far, only HBV monoinfected participants have been included in clinical trials. The results of these trials, in which JNJ-3989 was combined with a treatment like Entecavir or Tenofovir, were very promising and indicated a rapid decline in HBsAg levels. A new phase II study is currently recruiting, and evaluating the safety and efficacy of JNJ-3989 in people who are co-infected with HDV. 

REP 2139-Mg

REP 2139-Mg is a "nucleic acid-based amphipathic polymer (NAP)" that works by preventing infected liver cells from releasing hepatitis B virus into healthy liver cells. It is being evaluated for use in combination with PEG-IFN and Tenofovir. A study indicated that this combination treatment lowered HBsAg levels, HBV DNA, and HDV RNA in some patients. Planning for Phase II trials for this drug in Europe is currently in progress.

Vir 2218 + Vir 3434

Vir 2218 is an HBV-targeted SiRNA that has the potential to stimulate an effective immune response and demonstrate direct antivial activity against HBV and HDV. Vir 3434 is a monoclonal antibody that targets HBsAg and is designed to remove HBV and HDV virus from the blood and block the entry of these viruses into liver cells. A phase 2 study of both of these drugs is currently recruiting participants. 

Ropeginterferon Alfa-2b (P1101)

P1101 is an immune response stimulator that has been shown to be effective in treatment of a rare blood disease called Essential Thrombocythemia. This drug, along with the drug anti-PD1, which falls into a group of drugs that assists the immune system in fighting off some types of cancers, is being evaluated to test its effectiveness in fighting off chronic hepatitis B and D infection. It is hoped that these drugs will help to achieve loss of HBsAg and ALT normalization. A phase 1 study of this drug combination is currently recruiting participants.  

HBV/HDV Entry Inhibitor & Interferon Alpha Receptor Agonist

These drugs are in the very early stages and have not yet been named - they are both in development by Assembly Biosciences and will work to prevent HDV and HBV from entering healthy liver cells by blocking receptor mechanisms on the healthy cells.

GI-18000

GI-18000 is an "immune response stimulator" that works by causing the host's T-cells to target and fight the infected liver cells.


For current clinical trials for hepatitis delta click here.

Updated November 2022