Currently there is no approved treatment for acute or chronic HDV infection. Pegylated interferon alpha is the only drug that has been shown to be somewhat effective against HDV. It acts by stimulating the body's immune system to get rid of the virus. A small percentage (<30%) experience remission when injected weekly over 48 weeks. Oral nucleosides approved for hepatitis B have been used for HDV if interferon therapy is not possible and there is a high hepatitis B viral load. But these have not been very effective.
Currently, there is more hope for people diagnosed with Hepatitis D with promising new drugs in development. For more information about clinical trials click here.
Drugs in Development for Hepatitis D
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. This drug is now granted "Orphan Drug Designation" by the FDA.
This drug is an “entry inhibitor” that inhibits virus entry into hepatocytes (liver cells) and has shown activity against the hepatitis B virus. 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 hepatitis D viral levels. It has been granted PRIME Eligibility by the European Medicines Agency, a status that promotes support in development of drugs that target an unmet medical need. In October 2018 it was granted a similar designation by the FDA, Breakthrough Therapy designation.
This drug works by targeting the protein assembly process, preventing the production of new virus particles. In a current clinical trial, Lonafarnib combined with Ritonavir has shown promise in reducing hepatitis D viral levels, and the FDA has granted it fast-track status since this class of drugs have been developed for the treatment of cancers and have been shown to be safe.
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.
This compound is known as a “Nucleic acid-based Amphipathic
Polymer” (NAP) which inhibits the release of hepatitis B surface antigen (HBsAg) from infected liver cells and is being evaluated for hepatitis D virus in combination with PEG IFN.
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.
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.