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 and no longer recruiting); Lonafarnib + PEG IFN Lambda & Ritonavir - Phase II (not yet recruiting) |
FDA Breakthrough Therapy DesignationFDA Fast Track DesignationFDA Orphan Drug DesignationEMA Orphan Drug DesignationEMA PRIME |
Hepcludex (Formerly Myrcludex B)
|
Entry Inhibitor |
Gilead Sciences, Inc. |
Monotherapy: Conditional approval by EMA & Biologics License Application filed with FDA - ongoing Phase III and Phase II trials |
EMA PRIMEFDA Breakthrough Therapy DesignationFDA Orphan Drug DesignationPromising Innovative Medicine (PIM) Designation by British MHRA |
BJT-778 |
Monoclonal Antibody |
BlueJay Therapeutics |
Phase IIA |
EMA PRIME |
JNJ 3989 + Nucleos(t)ide Analog |
RNA Interference Compound |
Janssen Research & Development, LLC |
Phase II (not currently recruiting) |
N/A |
REP 2139 - Mg (in combination with PEG-IFN and Tenofovir) |
HBsAg Inhibitor |
Replicor, Canada |
Compassionate Access Program available In France, Austria, Israel, Italy, and Turkey; Phase II clinical trial planned enrollment starting in France and USA, Q1 of 2024
|
N/A |
Tobevibart + Elebsiran |
SiRNA Immune Response Stimulator/HBsAg Inhibitor/Entry Inhibitor |
Vir Biotechnology |
Phase II (recruiting) |
N/A |
HH-003 |
Entry Inhibitor |
Huahui Health |
Phase IIb (recruiting) |
N/A |
Hepalatide |
NTCP Target |
Shanghai HEP Pharmaceuticals |
Phase IIa (recruiting) |
N/A |
HH-006 |
Entry Inhibitor |
Huahui Health |
Phase I |
N/A |
ABI-6250 & Interferon Alpha Receptor Agonist |
Small Molecule Entry Inhibitor |
Assembly BioSciences |
Pre-clinical |
N/A |
GI-18000 |
Immune Response Stimulator |
GlobeImmune, USA |
Pre-clinical |
N/A |
Chart Updated March 2024
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 Co-transporting Polypeptide, HBsAg = Hepatitis B Surface Antigen, RNA = Ribonucleic Acid, SiRNA = Small Interfering RNA (a strand of synthetic RNA designed to specifically target a particular messenger RNA for destruction), 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 IFN-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 their Phase III D-LIVR clinical trial and topline data looks promising. The LOWR6 study, which is also investigating use of lonafarnib and ritonavir for treatment of hepatitis delta, is also currently in phase 3 trials (no longer recruiting). 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 sometime in 2024. In April of 2023, the drug was approved for prescription in the wider European Union and the UK. 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 participants, 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.
BJT-778
BJT-778 is a monoclonal antibody against hepatitis B surface antigen (anti-HBsAg mAb). This drug neutralizes and clears hepatitis B and hepatitis D virions and depletes HBsAg-containing subviral particles, which may help to reconstitute an individual’s antiviral immunity and contribute to functional cure for chronic hepatitis B. The drug is in Phase IIa clinical trials and has recently received EMA PRIME designation.
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. Previously, only HBV mono-infected 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 has completed enrollment and is 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 France and the United States is currently in progress and enrollment is planned for early 2024. A compassionate access program for use of this drug is currently available in Austria, France, Israel, Italy, and Turkey.
Tobevibart & Elebsiran
Elebsiran is an HBV-targeted SiRNA that has the potential to stimulate an effective immune response and demonstrate direct antiviral activity against HBV and HDV. Tobevibart 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.
HH-003
HH-003 is a novel entry inhibitor for HBV & HDV. It has the potential to become a new standard of care that offers functional cure, standalone or in combination with other therapeutics, for patients suffering from chronic HBV infection or HBV/HDV co-infection. A phase 2 study is currently recruiting participants.
Hepalatide
Hepalatide works by targeting NTCP (Sodium/Taurocholate Co-transporting Polypeptide). A Phase 2 study to evaluate efficacy in people living with chronic hepatitis D is currently recruiting participants.
HH-006
HH-006 has the same target as HH-003 and is formulated for subcutaneous (under the skin) injection. HH-006 is also suited for a specific subset of the patient population suffering from hepatitis B and D. This drug will enter Phase 1 clinical trials in the near future.
ABI-6250 & Interferon Alpha Receptor Agonist
These drugs 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.