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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 end of 2022)         
 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; w/ PEG-INF: Phase 2B 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-INF and Tenofovir)
 HBsAg Inhibitor
 Replicor, Canada
 Phase II planning in progress (Europe)

 

 N/A
ATI-2173 (in combination with Tenofovir)
ASPIN
Antios Therapeutics
Phase 2
N/A
 GI-18000
 Immune Response   Stimulator
 GlobeImmune, USA
 Pre-clinical
 N/A
Chart Updated June 2022

Glossary:
 

Terms: HBV = Hepatitis B Virus, CHB = Chronic Hepatitis B, HDV = Hepatitis Delta Virus, CHD = Chronic Hepatitis Delta, PEG-INF = Pegylated interferon, NTCP = Sodium/Taurocholate Cotransporting Polypeptide, HBsAg = Hepatitis B Surface Antigen, RNA = Ribonucleic Acid, ASPIN = Active Site Polymerase Inhibitor Nucleotide, 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 (INF-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 the end of 2022. 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. A study also showed promise for Myrcludex B (Hepcludex) when combined with PEG-INF in reducing hepatitis delta viral levels. Phase II trials to investigate this combination are still ongoing. Gilead Sciences, Inc. is currently 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 hepatiitis 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.

ATI-2173

ATI-2173 is an "Active Site Polymerase Inhibitor Nucleotide" (ASPIN). This is a fairly common type of antiviral, used in HCV and HBV, and even being researched for coronavirus. This drug works to stop transcription, or the process by which the information in a strand of DNA is copied into a new molecule of messenger RNA. ATI-2173 has significant potential to be a key component of a synergistic combination therapy to cure HBV. Combining ATI-2173 with a chain-terminating drug such as Tenofovir or Entecavir could shut down the HBV polymerase and all viral replication. A Phase 2 clinical trial of ATI-2173 with Tenofovir is currently underway.

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 June 2022