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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          
 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 & ongoing Phase III; w/ PEG-INF: Phase 2B
 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 Initiating
 FDA/EMA Orphan Drug Designation
 FDA Fast Track Designation
 FDA Breakthrough Therapy Designation
 Ezetimibe
 NTCP Inhibitor
 Ziauddin University   Hospital,   Pakistan
 Phase II
 N/A
JNJ 3989 + Nucleos(t)ide Analog
RNA Interference Compound
Janssen Research & Development, LLC
Phase II
N/A
 REP 2139 - Mg (in combination with PEG-INF and Tenofovir) and Ca
 HBsAg Inhibitor
 Replicor, Canada
 Phase II

 

 N/A
ATI-2173
ASPIN
Antios Therapeutics
Phase 2a
N/A
 GI-18000
 Immune Response   Stimulator
 GlobeImmune, USA
 Pre-clinical
 N/A
Chart Updated October 2021

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, 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

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. In a recent study, Lonafarnib combined with Ritonavir showed promise in reducing hepatitis delta virus levels. Eiger Biopharmaceuticals is currently enrolling patients in Phase III clinical trials. It 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. 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, partially to investigate the long-term effects of Hepcludex. 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. A phase II study showed the ability of combination therapy with ritonavir and Lonafarnib to reduce hepatitis delta virus levels. PEG-IFN-λ has been granted Breakthrough Therapy and Fast Track Designation by FDA, and Orphan Drug Designation by the FDA and EMA. A phase III trial to investigate the safety and efficacy of PEG-INF lambda is not currently recruiting, but will be underway soon.

Ezetimibe

Ezetimibe is currently being used as a treatment to lower cholesterol. Now being studied for effectiveness against hepatitis delta, it works by inhibiting NTCP, the receptor required for hepatitis delta to enter and infect liver cells. It is unclear if this clinical trial is still recruiting at this time.

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, 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 evaluating the safety and efficacy of JNJ-3989 in people who are co-infected with HDV. 

REP 2139-Mg and Ca

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. Phase II study indicated that this combination treatment lowered HBsAg levels, HBV DNA and HDV RNA in some patients.

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 2a 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 October 2021