Drug Watch

Drugs in Development for Hepatitis Delta

Drug

Mechanism

Company

Clinical Trial Phase

Designations

 Lonafarnib
 Prenylation Inhibitor
 Eiger BioPharma, USA
 Phase III          
 FDA Breakthrough Therapy Designation
 FDA Fast Track Designation
 FDA Orphan Drug Designation
 EMA Orphan Drug Designation
 EMA PRIME 
 Myrcludex B (Bulevirtide)
 Entry Inhibitor
 MYR-GmbH, Germany
 Phase III
 EMA PRIME
 FDA Breakthrough Therapy   Designation
 FDA Orphan Drug Designation
 Lambda (Pegylated Interferon)
 Immune Response Stimulator
 Eiger BioPharma, USA
 Phase II
 FDA Orphan Drug Designation
 FDA Fast Track Designation
 Ezetimibe
 NTCP Inhibitor
 Ziauddin University Hospital,   Pakistan
 Phase II
 N/A
 REP 2139
 REP 2165
 HBsAg Inhibitor
 Replicor, Canada
 Phase II
 N/A
 GI-18000
 Immune Response   Stimulator
 GlobeImmune, USA
 Pre-clinical
 N/A
 ALN-HD
 RNAi Gene Silencer
 Alnylam, USA 
 Pre-clinical
 N/A
 N/A
 RNA Interference
 Somagenetics, USA 
 Pre-clinical
 N/A
 ATI-2173
 N/A
 Antios Therapeutics, USA
 Pre-clinical
 N/A

Drug Watch chart updated March 2019.

Glossary:
 

Terms: HBV = Hepatitis B, CHB = Chronic hepatitis B, HDV = Hepatitis D, CHD = Chronic hepatitis D, Hepatocytes = liver cells, NTCP = Sodium/taurocholate cotransporting polypeptide, FDA = U.S. Food and Drug Administration, EMA = European Medicines Agency, NIH = National Institutes of Health,

Designations: FDA Orphan Drug Designation = FDA Fast Track Designation = , FDA Breakthrough Therapy Designation = , EMA PRIME Eligibility Designation = 

Lonafarnib

Lonafarnib is a well-characterized, first-in-class orally active drug that inhibits HDV replication inside liver cells by blocking an important step of the virus life cycle, preventing the production of new virus particles. Lonafarnib has been dosed in over 120 HDV-infected patients across international academic centers and is currently in Phase III clinical trials for HDV. Lonafarnib has been granted Orphan Drug designation by the FDA and EMA, Fast Track Designation and Breakthrough Therapy Designation by the FDA and PRIME Eligibility Designation by the EMA. 

Myrcludex B

Myrcludex B, also known as Bulevirtide, is an “entry inhibitor” that inhibits virus entry into hepatocytes and has shown activity against HBV. It may also hinder the establishment of HDV infection by breaking the cycle of infection of the liver cell and possibly re-infection. A recent study showed promise for Myrcludex B when combined with PEG-INF in reducing HDV viral levels. Myrcludex B is entering into Phase III clinical trials in 2019 at selected sites internationally. It has been granted PRIME Eligibility by the EMA, a status that promotes support in development of drugs that target an unmet medical need. In October 2018 it was granted Breakthrough Therapy Designation by FDA.

Pegylated Interferon Lambda

Pegylated-interferon-lambda (PEG-IFN-λ) is a well-characterized, late-stage, first in class, type III interferon that stimulates cell-mediated immune responses that are critical for the development of host protection during viral infections.  PEG-IFN-λ is currently included in a Phase II combination study with Lonafarnib at the NIH.  PEG-IFN-λ is an investigational agent and not yet approved for any indication.  PEG-IFN-λ has been granted Orphan Designation and Fast Track Designation by FDA.

Ezetimibe

Currently used to lower cholesterol in the blood, Ezetimibe is being studied for effectiveness against hepatitis D. Ezetimibe possesses pharmacophore features to inhibit NTCP, the receptor required for HBV and HDV hepatocyte entry.

REP 2139 and REP 2165 (REP-401 Protocol)

These compounds are “Nucleic acid-based Amphipathic Polymers” (NAP), which inhibit the release of HBsAg from infected liver cells. They are being evaluated for effectiveness against HDV in combination with TDF and PEG-IFN. Results from their small Phase II clinical trial indicated that this combination treatment lowered HBsAg, HBV DNA and HDV RNA in some patients.

GI-18000

The company has the potential to develop its GI-18000 Tarmogen to cause a T cell immune response against cells infected with HDV and thereby improve outcomes. Globeimmune’s strategy is to identify molecular targets that distinguish diseased cells from normal cells and activate the immune system to selectively target and eliminate only the diseased cells. 

ALN-HDV

ALN-HDV is currently in the pre-clinical This approach is being used for both the hepatitis B and hepatitis D virus to  "silence" the viral RNA with compounds that interfere with and cause the destruction of the viral genome (e.g. stop replication of the virus). 

For current clinical trials for hepatitis D click here.

Updated February 2019.