HBVPRES/2-48CONS-MYR (known as Bulevirtide or Myrcludex B) was developed as an agent bind and inactivate the hepatocyte surface protein sodium taurocholate cotransporting polypeptide (SLC10A1 or NTCP). By blocking NTCP, the drug misdirects hepatitis B virus (HBV) and co-infecting hepatitis D virus (HDV) to an unproductive pathway and thereby prevents infection of the cell. Because NTCP is involved in the bile acid transport cycle, the blockade of this target by myrcludex B can potentially be used for the treatment of various metabolic and inflammatory diseases. Myrcludex B is going to participate in phase 3 trial for patients with chronic hepatitis D, however, the study is not yet recruited. The drug successfully completed phase II clinical trial for the patients with chronic hepatitis B and D. In addition, myrcludex B has been studied during preclinical research as a potential treatment of dyslipidemias, non-alcoholic steatohepatitis; primary biliary cirrhosis.
Approval Year
PubMed
| Title | Date | PubMed |
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| First-in-human application of the novel hepatitis B and hepatitis D virus entry inhibitor myrcludex B. | 2016 Sep |
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| Treatment of chronic hepatitis D with the entry inhibitor myrcludex B: First results of a phase Ib/IIa study. | 2016 Sep |
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| The NTCP-inhibitor Myrcludex B: Effects on Bile Acid Disposition and Tenofovir Pharmacokinetics. | 2018 Feb |
| Substance Class |
Protein
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MYRCLUDEX B
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PRIMARY | Myrcludex B is an experimental drug for the treatment of hepatitis B and D. The first Phase IIa clinical trials with 40 patients concluded in 2014, finding that the drug was well tolerated and, as far as can be said with the limited data, effective against hepatitis B.Mechanism of action:The hepatitis B virus uses its surface lipopeptide pre-S1 for docking to mature liver cells via their sodium/bile acid co-transporter (NTCP) and subsequently entering the cells. Myrcludex B is a synthetic N-acetylated pre-S1 that can also dock to NTCP, blocking the virus's entry mechanism.The drug is also effective against hepatitis D because the hepatitis D virus is only infective in the presence of a hepatitis B virus infection. | ||
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ACTIVE MOIETY |
Results: Myrcludex B was well tolerated and no serious or relevant AEs representing off-target effects, and no immunogenic effects were observed up to the highest applied dose of 20 mg (intravenously). Myrcludex B showed dose-dependent pharmacokinetics, best described by a 2-compartment target-mediated drug disposition model. Bioavailability of the subcutaneous application was large (85%). Inter-individual variability was moderate. The pharmacokinetic model suggested that subcutaneous doses of 10 mg and above reach a target saturation of over 80% for at least 15 h.
Conclusions: Myrcludex B showed excellent tolerability up to high doses. Pharmacologic properties followed a 2-compartment target-mediated drug disposition model. These findings are vital for planning of further multiple dose efficacy trials in patients.
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ACTIVE MOIETY |
RESULTS: Myrcludex-B efficiently prevented viral spreading from the initially infected human hepatocytes, as demonstrated by the lack of increase in viremia, antigen levels and amount of HBcAg-positive human hepatocytes determined 6 weeks after treatment. Myrcludex-B efficiently blocked HBV dissemination also when treatment was started in the ramp-up phase of infection, in mice displaying moderate levels of circulating virions (median 3 10(6)HBV DNA copies/ml). Notably, after 6 weeks of treatment, not only the amount of HBcAg-positive hepatocytes, but also intrahepatic cccDNA loads, remained comparable to values found in mice sacrificed 3 weeks post-infection. In none of the experimental settings, drug administration affected human hepatocyte half-life or altered virion productivity.
CONCLUSIONS: Myrcludex-B efficiently not only prevented HBV spreading from infected human hepatocytes in vivo, but also hindered amplification of the cccDNA pool in initially infected hepatocytes. Administration of an entry inhibitor, possibly used in combination with current HBV drugs, may improve patients' treatment outcome.
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ACTIVE MOIETY |
Originator: INSERM, University of Heidelberg, Vision7; Developer: Hepatera, MYR GmbH, Vision7
Class: Antiviral, Lipopeptide; Mechanism of Action: Cell surface receptor antagonist, Sodium-bile acid cotransporter-inhibitor, Virus internalisation inhibitor; Orphan Drug Status: No; On Fast track: No; New Molecular Entity: Yes; Highest Development Phases: Phase II for Hepatitis B, Hepatitis D; Most Recent Events: 25 May 2016 Hepatera and MYR GmbH initiate a phase II MYR 203 trial for Hepatitis B and hepatitis D (Combination therapy) in Russia, 22 Mar 2016 Phase-II clinical trials in Hepatitis D (Combination therapy) in Germany (SC), 22 Mar 2016 Phase-II clinical trials in Hepatitis B (Combination therapy) in Germany (SC)
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| MOL_WEIGHT:NUMBER AVERAGE(CALCULATED) | CHEMICAL |
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