Bulevirtide-gmod

CAS 2012558-47-1.

MF C₂₄₈H₃₅₅N₆₅O₇₂ MW 5399 g/mol

FDA 2026, APPROVALS 2026, 5/22/2026, Hepcludex, WKM56H3TLB

To treat chronic hepatitis delta virus infection in adults without cirrhosis or with compensated cirrhosis

N-myristoyl-glycyl-L-threonyl-L-asparagyl-L-leucyl-L-seryl-L-valyl-L-prolyl-L-asparagyl-L-prolyl-L-leucyl-glycyl-L-phenylalanyl-L-phenylalanyl-L-prolyl-L-alpha-aspartyl-L-histidyl-L-glutaminyl-L-leucyl-L-alpha-aspartyl-L-prolyl-L-alanyl-L-phenylalanyl-glycyl-L-alanyl-L-asparagyl-L-seryl-L-asparagyl-L-asparagyl-L-prolyl-L-alpha-aspartyl-L-tryptophyl-L-alpha-aspartyl-L-phenylalanyl-L-asparagyl-L-prolyl-L-asparagyl-L-lysyl-L-alpha-aspartyl-L-histidyl-L-tryptophyl-L-prolyl-L-alpha-glutamyl-L-alanyl-L-asparagyl-L-lysyl-L-valyl-glycinamide

(4S)-4-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-4-amino-2-[[(2S)-1-[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-4-amino-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-1-[(2S)-4-amino-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S,3R)-3-hydroxy-2-[[2-(tetradecanoylamino)acetyl]amino]butanoyl]amino]-4-oxobutanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]-3-methylbutanoyl]pyrrolidine-2-carbonyl]amino]-4-oxobutanoyl]pyrrolidine-2-carbonyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-3-phenylpropanoyl]pyrrolidine-2-carbonyl]amino]-3-carboxypropanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-3-carboxypropanoyl]pyrrolidine-2-carbonyl]amino]propanoyl]amino]-3-phenylpropanoyl]amino]acetyl]amino]propanoyl]amino]-4-oxobutanoyl]amino]-3-hydroxypropanoyl]amino]-4-oxobutanoyl]amino]-4-oxobutanoyl]pyrrolidine-2-carbonyl]amino]-3-carboxypropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-carboxypropanoyl]amino]-3-phenylpropanoyl]amino]-4-oxobutanoyl]pyrrolidine-2-carbonyl]amino]-4-oxobutanoyl]amino]hexanoyl]amino]-3-carboxypropanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-5-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[(2-amino-2-oxoethyl)amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-5-oxopentanoic acid

Bulevirtide-gmod, sold under the brand name Hepcludex, is the first and only FDA-approved medication for treating chronic hepatitis delta virus (HDV) infection in adults. Developed by Gilead Sciences, it received accelerated approval from the U.S. Food and Drug Administration (FDA) on May 22, 2026, filling a critical gap for patients with this severe viral liver disease.

Indication and Clinical Use

• Target Patient Profile: Approved for adults with chronic HDV who have compensated cirrhosis or no cirrhosis.
• The Clinical Need: HDV only occurs as a co-infection in individuals who already have Hepatitis B (HBV). It is considered the most aggressive form of viral hepatitis, often accelerating liver scarring (fibrosis), liver failure, and liver cancer.
• Basis of Approval: The FDA granted accelerated approval based on Phase 3 MYR301 study data, which demonstrated a significant reduction in viral HDV RNA and the normalization of alanine aminotransferase (ALT) liver enzymes.

Mechanism of Action

Bulevirtide-gmod is a first-in-class entry inhibitor. It works by binding to and blocking the sodium taurocholate co-transporting polypeptide (NTCP) receptor on liver cells. Because HDV and HBV rely on this specific receptor to enter hepatocytes, the drug successfully disrupts the viral life cycle and prevents the virus from spreading to healthy liver cells.

Dosage and Administration

• Form: Supplied as a lyophilized powder for injection.
• Dose: The recommended dose is 8.5 mg once daily.
• Administration: Delivered via subcutaneous injection (under the skin).

Safety and Side Effects

• Boxed Warning: The drug carries a prominent warning regarding the risk of severe acute exacerbations of hepatitis D and B if treatment is discontinued. Stopping the medication can cause severe, life-threatening viral flares, requiring close medical monitoring for at least 6 months post-treatment.
• Common Side Effects: The most frequent adverse reactions of patients) include:
  • Injection site reactions
  • Headache
  • Abdominal pain
  • Fatigue
  • Pruritus (itching)

Bulevirtide, sold under the brand name Hepcludex, is an antiviral medication used for the treatment of chronic hepatitis D (in the presence of hepatitis B).^[8]

The most common side effects include raised levels of bile salts in the blood and reactions at the site of injection.^[8]

Bulevirtide works by attaching to and blocking a receptor (target) through which the hepatitis delta and hepatitis B viruses enter liver cells.^[8] 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.^[8]

Bulevirtide was approved for medical use in the European Union in July 2020,^[8] and in Canada in August 2025.^[5]

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.^[8][10]

Pharmacology

Mechanism of action

Bulevirtide binds and inactivates the sodium/bile acid cotransporter, blocking both hepatitis B and hepatitis D viruses from entering hepatocytes.^[11]

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-S1^[12][13] that can also dock to NTCP, blocking the virus’s entry mechanism.^[14]

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.^[14]

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.^[15] 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.^[16]

Structural formula

Bulevirtide is a 47-amino acid peptide with the following sequence:^[17]

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)

SYN

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2024073572&_cid=P11-MPNG4J-82875-1

PATENTS

• Therapy of atherosclerosis, primary biliary cirrhosis and nrlp3 inflammasome-associated disease by htcp inhibitorsPublication Number: EP-3392267-A1Priority Date: 2017-04-18
• Therapy of atherosclerosis, primary biliary cirrhosis and nrlp3 inflammasome-associated disease by htcp inhibitorsPublication Number: US-2018296634-A1Priority Date: 2017-04-18
• Therapy of atherosclerosis, primary biliary cirrhosis and nrlp3 inflammasome-associated disease by htcp inhibitorsPublication Number: US-2021196786-A1Priority Date: 2017-04-18
• Therapy of atherosclerosis, primary biliary cirrhosis and NRLP3 inflammasome-associated disease by HTCP inhibitorsPublication Number: US-10925925-B2Priority Date: 2017-04-18Grant Date: 2021-02-23
• Combination therapy of hbv and hdv infectionPublication Number: EP-3204030-B1Priority Date: 2014-10-07Grant Date: 2022-04-27
• Combination therapy of hbv and hdv infectionPublication Number: EP-4098273-A1Priority Date: 2014-10-07
• Combination therapy of hbv and hdv infectionPublication Number: US-2022040178-A1Priority Date: 2014-10-07

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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 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.
9.  “Hepcludex Product information”. Union Register of medicinal products. Retrieved 3 March 2023.
10.  “Summary of opinion: Hepcludex” (PDF). European Medicines Agency (EMA). 28 May 2020.
11.  Francisco EM (29 May 2020). “Hepcludex”. European Medicines Agency (EMA). Archived from the original on 15 June 2020. Retrieved 6 August 2020.
12.  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.
13.  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.
14.  Spreitzer H (14 September 2015). “Neue Wirkstoffe – Myrcludex B”. Österreichische Apothekerzeitung (in German) (19/2015): 12.
15.  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
16.  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.
17.  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.

Clinical data
Pronunciation	/bjuːˈlɛvɪrtaɪd/ byoo-LEH-vir-tyde
Trade names	Hepcludex
Other names	MyrB, Myrcludex-B[1]
License data	US DailyMed: Bulevirtide
Pregnancy category	AU: B1[2]
Routes of administration	Subcutaneous
ATC code	J05AX28 (WHO)
Legal status
Legal status	AU: S4 (Prescription only)[3][4][2]CA: ℞-only[5][6]UK: POM (Prescription only)[7]EU: Rx-only[8][9]
Identifiers
CAS Number	2012558-47-1
DrugBank	DB15248
ChemSpider	129157549
UNII	WKM56H3TLB
KEGG	D11877as salt: D11878
ChEMBL	ChEMBL4297711
Chemical and physical data
Formula	C248H355N65O72
Molar mass	5398.951 g·mol−1
3D model (JSmol)	Interactive image
SMILES
InChI

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