Bulevirtide 2mg powder for solution for injection vials

Background: Hepatitis D virus (HDV) is a defective virus requiring co-infection with hepatitis B virus (HBV) to replicate, occurring in 5% of HBV+ patients. Bulevirtide (BLV) is now the first-in-class specific anti-HDV agent, inhibiting HDV binding to NTCP, with good tolerability and good virological and biochemical response rates. Currently, little is known about its pharmacokinetic/pharmacodynamic (PK/PD), as well as potential drug-drug interaction (DDI) profile. In this work we provide a systematic review of the current knowledge on these aspects. Methods: A literature review of PK, PD and DDI profiles of BLV was conducted from Pubmed and EMA websites. Experimentally tested interactions and hypothetical mechanisms of interaction were evaluated, mostly focusing on usually co-administered anti-infective agents and other drugs interacting on NTCP. Results: BLV shows non-linear PK, due to target-mediated drug disposition, so its PK as well as PD is expected to be influenced by interactions of other drugs with NTCP, while it is not substrate of CYPs and ABC transporters. In-vivo investigated DDIs showed no clinically relevant interactions, but a weak inhibitory effect was suggested on CYP3A4 in a work when used at high doses (10 mg instead of 2 mg). In vitro, a weak inhibitory effect on OATP transporters was observed, but at much higher concentrations than the ones expected in vivo. Conclusions: The drug-drug interaction potential of BLV can be considered generally very low, particularly at the currently approved dose of 2 mg/day. Some attention should be paid to the coadministration of drugs with known binding and/or inhibition of NTCP.

Abstract licence: CC BY 4.0

Chronic hepatitis Delta (CHD) is a rare and severe form of chronic viral hepatitis. Until recently, the only therapeutic approach has been the off‐label use of a 48 weeks course of PegInterferon alpha (PegIFNα), that was characterized by suboptimal efficacy and burdened by significant side effects that limited treatment applicability in patients with advanced liver disease. In July 2020, European Medicines Agency (EMA) conditionally approved the entry inhibitor Bulevirtde (BLV) at the dose of 2 mg/day for the treatment of adult patients with compensated CHD. Efficacy and safety of BLV in CHD have been evaluated in clinical trials either as monotherapy or in combination with PegIFNα. These results were confirmed by real‐life studies, which also evaluated long‐term BLV monotherapy in patients with advanced compensated cirrhosis. Notwithstanding these promising results there are still several issues to be addressed, such as the optimal duration of the treatment, the rates of off‐therapy responses, as well as the long‐term clinical benefits. This review summarizes updated and current literature data about clinical trials and real‐life studies with BLV monotherapy and/or in combination with PegIFNα.

Abstract licence: CC BY 4.0