Bulevirtide

Hepatitis delta is a defective virus that borrows the hepatitis B surface antigen envelope, so it enters hepatocytes by the same route HBV does: the myristoylated N-terminal preS1 domain of large HBsAg docking with NTCP on the basolateral hepatocyte membrane. Bulevirtide is a synthetic copy of preS1 residues 2-48, myristoylated at the N-terminus and amidated at the C-terminus, which binds NTCP with sub-nanomolar affinity and occupies it competitively. Newly released virions cannot infect fresh hepatocytes and the infected cell pool declines as those cells turn over. NTCP is physiologically the hepatic bile salt uptake transporter, so blocking it produces a dose-dependent, asymptomatic rise in serum bile acids in essentially every treated patient — an expected pharmacological consequence rather than liver injury. Stopping the drug can precipitate a severe hepatitis flare, which is the basis of its boxed warning.

Targets: Sodium taurocholate co-transporting polypeptide (NTCP/SLC10A1), HDV and HBV hepatocyte entry

• · 8.5 mg once daily is the dose in the US label granted accelerated approval in May 2026. Optimal treatment duration is not established; it continues as long as it is producing a response.
• · The EU marketing authorisation is for 2 mg once daily, with or without a nucleos(t)ide analogue for underlying HBV. The MYR301 trial compared 2 mg and 10 mg daily against no treatment; both doses beat control, and the two doses were broadly similar at 48 weeks with some separation favouring higher exposure over longer follow-up. The US and EU landed on different doses from overlapping data — worth knowing if you read guidance from both regions.
• · Studied in MYR204 and related trials, where the combination produced higher rates of undetectable HDV RNA sustained off treatment than bulevirtide alone. It is not the labelled regimen but is used in specialist centres pursuing a finite-duration cure.

Work out your exact syringe units →

• very commonAsymptomatic bile salt elevation— Occurs in essentially all patients and is a direct consequence of NTCP blockade, not liver injury. It does not require dose reduction and reverses on stopping.
• very commonInjection-site reactions— Redness, itching and swelling; usually mild and improves with site rotation.
• commonHeadache
• commonPruritus— Likely related to the bile acid rise.
• commonEosinophilia
• uncommonSevere acute exacerbation of hepatitis on discontinuation— Boxed warning. Stopping bulevirtide can trigger a hepatitis flare severe enough to cause decompensation, so discontinuation must be planned and monitored, not abrupt.

• Decompensated cirrhosis — the approved indication covers compensated cirrhosis only, and use in decompensated disease has not been established as safe.
• Known hypersensitivity to bulevirtide.
• Abrupt unmonitored discontinuation, given the flare risk.
• Concomitant strong OATP1B1/1B3 inhibitors, which raise bulevirtide exposure substantially.

• conflictOATP1B1/1B3 inhibitors (e.g. cyclosporine, some HCV antivirals) — Markedly increase bulevirtide exposure; co-administration is not recommended.
• cautionNTCP substrate drugs and statins — By blocking NTCP, bulevirtide can raise systemic exposure to drugs that rely on this transporter for hepatic uptake, including some statins.
• synergypeginterferon alfa-2a — The combination produces higher rates of sustained HDV RNA suppression than either alone in trial settings.
• synergytenofovir / entecavir — Nucleos(t)ide analogues for the underlying HBV infection are commonly continued alongside bulevirtide and do not interact adversely.

• · HDV RNA and ALT at baseline and periodically during therapy to confirm response.
• · HBV DNA and HBsAg status.
• · Liver function tests for at least several months after any discontinuation, watching for a hepatitis flare.
• · Bile acid levels are commonly measured but a rise is expected and does not require action.

Prescription-only injectable. Fully authorised in the EU, UK and Switzerland; FDA accelerated approval granted May 2026 for chronic HDV in adults without cirrhosis or with compensated cirrhosis.

• Wedemeyer et al., MYR301 phase 3 trial of bulevirtide for chronic hepatitis delta, NEJM (trial)
• Hepcludex (bulevirtide-gmod) US prescribing information with boxed warning (label)
• EMA Hepcludex summary of product characteristics and EPAR (label)

A lipidated 47-residue peptide derived from the hepatitis B surface antigen preS1 domain. It binds and blocks NTCP, the sodium taurocholate co-transporting polypeptide, which both hepatitis B and hepatitis D use as their entry receptor. Blocking entry does not clear infected cells, so it suppresses rather than cures, and it is the first approved therapy specifically for chronic hepatitis D.

The predictable confusion is the bile acid rise: it is universal, on-target and asymptomatic, and stopping the drug for it discards an effective therapy for a lab abnormality that was expected. The other issue is duration - relapse after stopping is common, and optimal treatment length is not established.

• NTCP (SLC10A1) bile acid transporter — High; the physiological function is bile salt uptake

  Blocks HDV and HBV hepatocyte entry

• MYR301 Phase 3 · n=150 · 48 weeks · 2023

  Combined virological and biochemical response versus no treatment in chronic hepatitis D.

HDV RNA declines over the first months; ALT normalisation typically lags the virological response.

• ?Optimal treatment duration is genuinely unknown, and whether therapy can ever be stopped without relapse is unresolved.
• ?Whether combining with pegylated interferon improves durable response is still under study.