%0 Journal Article
%T Emerging drugs for hepatitis D.
%A Keskin O
%A Yurdaydin C
%J Expert Opin Emerg Drugs
%V 28
%N 2
%D 2023 12 27
%M 37096555
%F 3.912
%R 10.1080/14728214.2023.2205639
%X Chronic hepatitis delta (CHD) is the most severe form of chronic viral hepatitis. Until recently, its treatment consisted of pegylated interferon alfa (pegIFN) use.<BR>Current and new drugs for treating CHD. Virus entry inhibitor bulevirtide has received conditional approval by the European Medicines Agency. Prenylation inhibitor lonafarnib and pegIFN lambda are in phase 3 and nucleic acid polymers in phase 2 of drug development.<BR>Bulevirtide appears to be safe. Its antiviral efficacy increases with treatment duration. Combining bulevirtide with pegIFN has the highest antiviral efficacy short-term. The prenylation inhibitor lonafarnib prevents hepatitis D virus assembly. It is associated with dose-dependent gastrointestinal toxicity and is better used with ritonavir which increases liver lonafarnib concentrations. Lonafarnib also possesses immune modulatory properties which explains some post-treatment beneficial flare cases. Combining lonafarnib/ritonavir with pegIFN has superior antiviral efficacy. Nucleic acid polymers are amphipathic oligonucleotides whose effect appears to be a consequence of phosphorothioate modification of internucleotide linkages. These compounds led to HBsAg clearance in a sizable proportion of patients. PegIFN lambda is associated with less IFN typical side effects. In a phase 2 study it led to 6 months off treatment viral response in one third of patients.