Article · Wikipedia archive · Last revised Jun 1, 2026

Bulevirtide

Bulevirtide, sold under the brand name Hepcludex, is an antiviral medication used for the treatment of chronic hepatitis D.

Last revised
Jun 1, 2026
Read time
≈ 4 min
Length
980 w
Citations
39
Source
Wikipedia ↗
Bulevirtide
Clinical data
Pronunciation/bjuːˈlɛvɪrtaɪd/
byoo-LEH-vir-tyde
Trade namesHepcludex
Other namesMyrB, Myrcludex-B,1 bulevirtide-gmod
AHFS/Drugs.comhepcludex
License data
Pregnancy
category
  • AU: B12
Routes of
administration		Subcutaneous
Drug classAntiviral
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC248H355N65O72
Molar mass5398.951 g·mol−1
3D model (JSmol)
  • CCCCCCCCCCCCCC(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](Cc1ccccc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](Cc1ccccc1)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)NCC(N)=O)C(C)C)C(C)C)[C@@H](C)O
  • InChI=1S/C248H355N65O72/c1-16-17-18-19-20-21-22-23-24-25-38-75-193(327)265-118-196(330)304-205(133(15)316)241(378)295-163(104-188(256)322)224(361)283-152(91-127(6)7)216(353)303-175(122-315)232(369)306-204(129(10)11)248(385)313-88-53-74-182(313)239(376)301-172(107-191(259)325)246(383)312-87-50-70-178(312)235(372)291-150(89-125(2)3)209(346)268-120-195(329)274-154(93-135-56-32-27-33-57-135)217(354)296-168(95-137-60-36-29-37-61-137)242(379)308-83-49-72-180(308)237(374)294-167(111-201(339)340)230(367)286-157(98-140-115-261-123-269-140)220(357)277-148(76-78-183(251)317)213(350)282-151(90-126(4)5)215(352)300-173(112-202(341)342)247(384)307-82-47-68-176(307)233(370)273-132(14)208(345)279-153(92-134-54-30-26-31-55-134)210(347)267-119-194(328)271-130(12)206(343)280-160(101-185(253)319)226(363)302-174(121-314)231(368)288-161(102-186(254)320)225(362)299-171(106-190(258)324)245(382)311-86-52-73-181(311)238(375)293-166(110-200(337)338)229(366)285-156(96-138-113-263-144-64-41-39-62-142(138)144)219(356)290-165(109-199(335)336)227(364)284-155(94-136-58-34-28-35-59-136)218(355)298-170(105-189(257)323)244(381)310-85-51-71-179(310)236(373)292-162(103-187(255)321)223(360)275-146(66-43-45-80-249)212(349)289-164(108-198(333)334)228(365)287-158(99-141-116-262-124-270-141)221(358)297-169(97-139-114-264-145-65-42-40-63-143(139)145)243(380)309-84-48-69-177(309)234(371)278-149(77-79-197(331)332)211(348)272-131(13)207(344)281-159(100-184(252)318)222(359)276-147(67-44-46-81-250)214(351)305-203(128(8)9)240(377)266-117-192(260)326/h26-37,39-42,54-65,113-116,123-133,146-182,203-205,263-264,314-316H,16-25,38,43-53,66-112,117-122,249-250H2,1-15H3,(H2,251,317)(H2,252,318)(H2,253,319)(H2,254,320)(H2,255,321)(H2,256,322)(H2,257,323)(H2,258,324)(H2,259,325)(H2,260,326)(H,261,269)(H,262,270)(H,265,327)(H,266,377)(H,267,347)(H,268,346)(H,271,328)(H,272,348)(H,273,370)(H,274,329)(H,275,360)(H,276,359)(H,277,357)(H,278,371)(H,279,345)(H,280,343)(H,281,344)(H,282,350)(H,283,361)(H,284,364)(H,285,366)(H,286,367)(H,287,365)(H,288,368)(H,289,349)(H,290,356)(H,291,372)(H,292,373)(H,293,375)(H,294,374)(H,295,378)(H,296,354)(H,297,358)(H,298,355)(H,299,362)(H,300,352)(H,301,376)(H,302,363)(H,303,353)(H,304,330)(H,305,351)(H,306,369)(H,331,332)(H,333,334)(H,335,336)(H,337,338)(H,339,340)(H,341,342)/t130-,131-,132-,133+,146-,147-,148-,149-,150-,151-,152-,153-,154-,155-,156-,157-,158-,159-,160-,161-,162-,163-,164-,165-,166-,167-,168-,169-,170-,171-,172-,173-,174-,175-,176-,177-,178-,179-,180-,181-,182-,203-,204-,205-/m0/s1
  • Key:WQNDXLHKAMIGEX-WOAPPVHJSA-N

Bulevirtide, sold under the brand name Hepcludex, is an antiviral medication used for the treatment of chronic hepatitis D.89

The most common side effects include raised levels of bile salts in the blood and reactions at the site of injection.9

Bulevirtide works by attaching to and blocking a receptor (target) through which the hepatitis delta and hepatitis B viruses enter liver cells.9 By blocking the entry of the virus into the cells, it limits the ability of HDV to replicate and its effects in the body, reducing symptoms of the disease.9

Bulevirtide was approved for medical use in the European Union in July 2020,9 in Canada in August 2025,5 and in the United States in May 2026.11

Medical uses

Bulevirtide is indicated for the treatment of chronic hepatitis delta virus (HDV) infection in plasma (or serum) HDV-RNA positive adult patients with compensated liver disease.912

Hepatitis delta virus infection only occurs in individuals who have hepatitis B virus infection.11

Pharmacology

Mechanism of action

Bulevirtide binds and inactivates the sodium/bile acid cotransporter, blocking both hepatitis B and hepatitis D viruses from entering hepatocytes.13

The hepatitis B virus uses its surface lipopeptide pre-S1 for docking to mature liver cells via their sodium/bile acid cotransporter (NTCP) and subsequently entering the cells. Myrcludex B is a synthetic N-acylated pre-S11415 that can also dock to NTCP, blocking the virus's entry mechanism.16

Bulevirtide is also effective against hepatitis D because the hepatitis D virus uses the same entry receptor as the hepatitis B virus and is only effective in the presence of a hepatitis B virus infection.16

Pre-clinical data in mice suggests that pharmacological inhibition of NTCP-mediated bile salt uptake may also be effective to lower hepatic bile salt accumulation in cholestatic conditions. This reduces hepatocellular damage.17 An increased ratio of phospholipid to bile salts seen in bile upon NTCP inhibition may further contribute to the protective effect as bile salts are less toxic in presence of phospholipids.18

Chemistry

Bulevirtide is a 47-amino acid long lipopeptide with the following sequence:19

CH3(CH2)12CO-Gly-Thr-Asn-Leu-Ser-Val-Pro-Asn-Pro-Leu-Gly-Phe-Phe-Pro-Asp-His-Gln-Leu-Asp-Pro-Ala-Phe-Gly-Ala-Asn-Ser-Asn-Asn-Pro-Asp-Trp-Asp-Phe-Asn-Pro-Asn-Lys-Asp-His-Trp-Pro-Glu-Ala-Asn-Lys-Val-Gly-NH2 (C13H27CO-GTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPNKDHWPEANKVG-NH2)

History

The efficacy of bulevirtide was demonstrated in a multi-center, randomized, open-label, parallel-arm phase III trial.11 In Trial MYR301, participants were randomly assigned to immediate treatment with bulevirtide 8.5 mg once daily for 144 weeks or to delayed treatment with an observational period of 48 weeks followed by bulevirtide 8.5 mg once daily for 96 weeks.11

Society and culture

Bulevirtide was approved for medical use in the European Union in July 2020,9 in Canada in August 2025,5 and in the United States in May 2026.8 The US Food and Drug Administration granted the application for bulevirtide priority review, breakthrough therapy, and orphan drug designations.11

Names

Bulevirtide is the international nonproprietary name.20

Bulevirtide is sold under the brand name.Hepcludex.89

References

References

  1. Deterding K, Wedemeyer H (2019). "Beyond Pegylated Interferon-Alpha: New Treatments for Hepatitis Delta". AIDS Reviews. 21 (3): 126–134. doi:10.24875/AIDSRev.19000080. PMID 31532397. S2CID 202674681.
  2. "Hepcludex (bulevirtide acetate)". Therapeutic Goods Administration (TGA). 12 August 2024. Retrieved 12 October 2024.
  3. "Therapeutic Goods (Poisons Standard—June 2024) Instrument 2024". Federal Register of Legislation. 30 May 2024. Retrieved 10 June 2024.
  4. "Hepcludex (Gilead Sciences Pty Ltd)". Therapeutic Goods Administration (TGA). 13 September 2024. Retrieved 15 September 2024.
  5. "Hepcludex Product information". Health Canada. 8 August 2025. Retrieved 20 August 2025.
  6. "Summary Basis of Decision for Hepcludex". Drug and Health Products Portal. 29 September 2025. Retrieved 12 October 2025.
  7. "Hepcludex 2 mg powder for solution for injection - Summary of Product Characteristics (SmPC)". (emc). 30 March 2022. Retrieved 1 July 2022.
  8. "Hepcludex- bulevirtide injection, powder, lyophilized, for solution". DailyMed. 22 May 2026. Retrieved 29 May 2026.
  9. "Hepcludex EPAR". European Medicines Agency (EMA). 26 May 2020. Retrieved 12 August 2020. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  10. "Hepcludex Product information". Union Register of medicinal products. Retrieved 3 March 2023.
  11. "FDA Approves First Treatment for Chronic Hepatitis Delta Virus (HDV) Infection". U.S. Food and Drug Administration (FDA). 22 May 2026. Retrieved 29 May 2026. This article incorporates text from this source, which is in the public domain.
  12. "Summary of opinion: Hepcludex" (PDF). European Medicines Agency (EMA). 28 May 2020.
  13. Francisco EM (29 May 2020). "Hepcludex". European Medicines Agency (EMA). Archived from the original on 15 June 2020. Retrieved 6 August 2020.
  14. Volz T, Allweiss L, Ben MBarek M, Warlich M, Lohse AW, Pollok JM, et al. (May 2013). "The entry inhibitor Myrcludex-B efficiently blocks intrahepatic virus spreading in humanized mice previously infected with hepatitis B virus". Journal of Hepatology. 58 (5): 861–867. doi:10.1016/j.jhep.2012.12.008. PMID 23246506.
  15. Abbas Z, Abbas M (August 2015). "Management of hepatitis delta: Need for novel therapeutic options". World Journal of Gastroenterology. 21 (32): 9461–9465. doi:10.3748/wjg.v21.i32.9461. PMC 4548107. PMID 26327754.
  16. Spreitzer H (14 September 2015). "Neue Wirkstoffe – Myrcludex B". Österreichische Apothekerzeitung (in German) (19/2015): 12.
  17. Na+ -taurocholate cotransporting polypeptide inhibition has hepatoprotective effects in cholestasis in mice. Slijepcevic D, Roscam Abbing RLP, Fuchs CD, Haazen LCM, Beuers U, Trauner M, Oude Elferink RPJ, van de Graaf SFJ. Hepatology. 2018 Sep;68(3):1057-1069. doi: 10.1002/hep.29888
  18. Roscam Abbing RL, Slijepcevic D, Donkers JM, Havinga R, Duijst S, Paulusma CC, et al. (January 2020). "Blocking Sodium-Taurocholate Cotransporting Polypeptide Stimulates Biliary Cholesterol and Phospholipid Secretion in Mice". Hepatology. 71 (1): 247–258. doi:10.1002/hep.30792. PMC 7003915. PMID 31136002.
  19. Sauter M, Blank A, Stoll F, Lutz N, Haefeli WE, Burhenne J (September 2021). "Intact plasma quantification of the large therapeutic lipopeptide bulevirtide". Analytical and Bioanalytical Chemistry. 413 (22): 5645–5654. doi:10.1007/s00216-021-03384-7. PMC 8410713. PMID 34018034.
  20. World Health Organization (2018). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 80". WHO Drug Information. 32 (3). hdl:10665/330907.