Bulevirtide

In plain language

Bulevirtide is an antiviral for hepatitis D, the most severe form of viral hepatitis, sold as Hepcludex. It was approved in Europe in 2020 and received accelerated approval from the FDA in May 2026.

It is a copy of the part of hepatitis B's outer coat that the viruses use to enter liver cells, with a fatty tag added. By occupying the liver-cell entry receptor, it blocks hepatitis D from getting in, protecting the cells that are not yet infected.

For students

Bulevirtide is a 47-residue lipopeptide (about 5,399 Da) derived from the hepatitis B virus preS1 domain, myristoylated at the N-terminus. It competitively occupies the sodium-taurocholate co-transporting polypeptide (NTCP, SLC10A1), the bile acid transporter that HBV and HDV co-opt for entry, blocking virion engagement with the receptor.

HDV is a defective virus that requires HBV's surface proteins to propagate, so an entry inhibitor against the HBV preS1-NTCP interaction stops both. The MYR203 Phase 3 trial (n=150, published in NEJM 2022) showed HDV RNA declines and combined virologic plus biochemical response rates of about 56% at 48 weeks versus 0% on no treatment, supporting EU conditional approval (2020) and FDA accelerated approval (May 22, 2026) for HDV with compensated liver disease. Monitoring includes bile salt elevations (expected pharmacology) and liver function; the EU label requires more hepatic monitoring in decompensated disease, and monotherapy must be continued alongside nucleos(t)ide analogues to suppress HBV.

For researchers and instructors

Biochemistry. Viral entry via a host bile acid transporter (NTCP) is the structural lesson: the drug is a molecular decoy of a viral surface domain, a conceptually elegant "receptor sink" strategy; myristoylation both matches the viral original and tunes membrane association.

Pharmacology. 2 mg (or 10 mg in some regions) subcutaneous daily; expected pharmacology includes elevated conjugated bile salts; must be co-administered with HBV nucleos(t)ide therapy; liver monitoring per label.

Human evidence. MYR203 (n=150, NEJM 2022) is the pivotal trial; extension data to 240 weeks support durability; the FDA's accelerated approval pathway (May 22, 2026) requires confirmatory trials, which remain ongoing.

Teaching point. Teaches host-receptor decoys as antivirals, the dependency of HDV on HBV surface proteins, and accelerated approval obligations on sponsors.