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"Eliminate Hepatitis"—hepatitis B nucleoside drugs in market and in development

2017-07-28 来源:转载自第三方
28 July 2017
  There are 257 million patients suffering from hepatitis B in the world currently, and in its treatment, the progress is still limited. July 28 is the "World Hepatitis Day", the theme is for this year is "Eliminate Hepatitis". Today, we will summarize the hepatitis B nucleoside drugs both marketed and in development.
Marketed hepatitis B nucleoside drugs
  Lamivudine: lamivudine takes effect quickly, it can show efficacy after medication about 1 week, more than 80% of patients can occur significantly decreasing of hepatitis B virus DNA load within 2 months, about half a year, DNA of more than half patients are negative; lamivudine adapt to a wide range with low side effects. But drug resistance phenomenon will appear due to virus mutation, which limits the long-term application of lamivudine.
  Entecavir: The efficacy of entecavir is 300 times that of lamivudine, with an early response rate of over 90%. There is no virus mutation phenomenon with the drug within 2 years, and only 2% of patients with virus mutation about 3 years later. And it has less adverse reactions, good safety for long-term use, but the safety of pregnancy is not high.
  Adefovir dipivoxil: it solves the drug resistance problem of lamivudine. However, the use of high doses may cause renal damage in patients, so patients with long-term treatment of adefovir should be regularly monitored renal function in the treatment process.
  Tenofovir dipivoxil: The treatment effect of tenofovir dipivoxil is consistent with entecavir, it is also the first-line drug recommended by guideline of hepatitis B prevention and controls. Its pregnancy safety is higher, But the main adverse reaction is renal tubular injury, patients with long-term medication should be alert to renal insufficiency and low phosphorus bone disease.
  Telbivudine: It was approved by FDA in 2006 and by SFDA in 2007. The pregnancy safety of Telbivudine is good, and can be used as blocking medication in pregnant women with high viral load. But the main adverse reaction is muscle damage, and patients need to detect creatine kinase regularly.
Hepatitis B nucleoside drugs in development
ARB-1467 and ARB-1740
  Both of them were developed by Arbutus Biopharma and used Arbutus’s proprietary Lipid Nanoparticle (LNP) platform. ARB-1467 contains three RNAi trigger factors for all four HBV transcripts that reduce all viral antigen levels and reduce the covalent closed-loop DNA (cccDNA) and other DNA levels of hepatitis B virus in preclinical trials. In Phase 2 clinical trials, the researchers found that a single treatment can significantly reduce hepatitis B surface antigen (HBsAg) level in serum, multiple treatment can play an additional effect.
  Compared to ARB-1467, ARB-1740 uses different RNAi trigger molecules. In the preclinical trial, ARB-1740 demonstrated greater potential. The new therapy has entered Phase 2 clinical trials, the data are expected to be announced in the second half of this year.
  ALN-HBV was developed by Alnylam Pharmaceuticals. Preclinical trials have shown that it significantly reduces HBsAg levels in rodent-derived hepatitis B models. Currently, it is in the 1/2 phase of clinical trials to explore the safety and tolerability of this therapy.
  BB-HB-331, developed by Benitec Biopharma, has three shRNAs that target highly conserved sequences in the genome of the hepatitis B virus, thereby inhibiting viral replication and viral protein production, resulting in long-term therapeutic effects. Preclinical data indicate that this therapy can effectively reduce hepatitis B virus DNA levels and HBsAg levels in human liver cells, as well as in animal models. In addition, hepatitis B virus cccDNA levels also decreased.
  LUNAR-HBV is a combination of Arcturus and Janssen Pharmaceuticals, which targets all transcripts of hepatitis B virus. Last year, this therapy reported the results of pharmacokinetic analysis.
In the choice of hepatitis B antiviral drugs, specific cases of patients should be considered to decide the drugs and treatment programs. At the same time, we hope that these new drugs in research can bring new hope to the patients.

Edited by Suzhou Yacoo Science Co., Ltd. 


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