Methods for treating HcV

A recipient, patient technology applied in the field of treatment of HcV

Inactive Publication Date: 2020-05-15
ABBVIE INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Despite advances in IFN-free regimens, currently available treatments in the transplant population still require RBV and / or require 24 weeks of treatment

Method used

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  • Methods for treating HcV
  • Methods for treating HcV
  • Methods for treating HcV

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0188] Example 1. Clinical modeling of DAA combination therapy without interferon

[0189] Treatment regimens involving the administration of Compound 1 and Compound 2 were evaluated using the clinical model described in U.S. Patent Application Publication No. 2013 / 0102526, filed October 19, 2012, and entitled "Methods of Treating HCV," The aforementioned US patent application publications are incorporated herein by reference in their entirety. These treatment regimens included the administration of Compound 1 and Compound 2, but not the administration of interferon or ribavirin. Interferon nonresponders are expected to have comparable SVR rates.

[0190] figure 1 Predicted median SVR percentages and 90% SVR confidence intervals for genotype 1 untreated individuals treated with a 2-DAA regimen consisting of Compound 1 (400 mg once daily) and Compound 2 (120 mg once daily) are shown. Different treatment durations were evaluated. The predicted SVR rate for 12 weeks of treatm...

example 2

[0198] Example 2. Combination of Compound 1 and Compound 2 in vitro

[0199] Figure 9 It was shown that the combination of Compound 1 and Compound 2 exhibited a significant synergistic effect on HCV inhibition as tested in HCV GT1b Con-1 replicating cells. Results were generated using the Prichard and Shipman model (Prichard et al. ANTIVIRAL RESEARCH 14:181-205 (1990)).

[0200] Compound 1 inhibits the replication of HCV stable subgenomic replicons containing the NS3 gene from GT 1a, 1b, 2a, 3a, 4a or 6a, where EC 50 Values ​​ranged from 0.85 to 2.8 nM. Notably, compound 1 was potent against replicon containing GT3a protease, in which EC 50 The value is 1.6nM. Compound 1 retained its activity against common GT1a and Ib variants at NS3 amino acid positions 155 and 168, which confer resistance against other HCV protease inhibitors (Pis). Resistant colony selection studies in GT1a and 1b subgenomic replicon cells identified A156T in GT1a and A156V in GT1b as the most common...

example 3

[0210]Example 3. High SVR in HCV Genotype 1 (GT1 ) Non-Cirrhosis-Naive Patients or Pegylated Interferon / Ribavirin Nonresponders Treated with Combination of Compound 1 and Compound 2

[0211] Compounds 1 and 2 were characterized by potent pan-genotype in vitro antiviral activity against major HCV genotypes (GTs), including activity against key known resistance-associated variants and a high resistance selection barrier. Monotherapy with Compound 1 or Compound 2 resulted in a mean 4-log reduction in HCV plasma viral load from baseline in GT1-infected individuals with or without compensated cirrhosis 10 IU / mL.

[0212] In this Phase 2 study, 12 weeks of treatment with Compound 1 and Compound 2 were evaluated in HCV GT1 -infected individuals without cirrhosis. Non-cirrhotic GT1-infected treatment-naïve (TN) individuals or pegIFN / RBV-neutral responders received 200 mg Compound 1 + 120 or 40 mg Compound 2 once daily for 12 days weeks, and followed up for 24 weeks. Efficacy was m...

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Abstract

The present invention features interferon-free therapies for the treatment of HCV. Preferably, the treatment is over a shorter duration of treatment, such as no more than 12 weeks. In one aspect, thetreatment comprises administering at least two direct acting antiviral agents to a subject with HCV infection, wherein the treatment lasts for 12 weeks and does not include administration of either interferon or ribavirin, and said at least two direct acting antiviral agents comprise (a) Compound 1 or a pharmaceutically acceptable salt thereof and (b) Compound 2 or a pharmaceutically acceptable salt thereof.

Description

technical field [0001] The present invention relates to an interferon-free and ribavirin-free treatment of hepatitis C virus (HCV). Background technique [0002] HCV is an RNA virus belonging to the Hepacivirus genus in the Flaviviridae family. Enveloped HCV virions contain a positive-strand RNA genome that encodes all known virus-specific proteins in a single uninterrupted open reading frame. The open reading frame comprises about 9500 nucleotides and encodes a single large polymeric protein of about 3000 amino acids. Polymeric proteins include core protein, envelope proteins E1 and E2, membrane-bound protein p7, and nonstructural proteins NS2, NS3, NS4A, NS4B, NS5A, and NS5B. [0003] Chronic HCV infection is associated with progressive liver disease, including cirrhosis and hepatocellular carcinoma. Chronic hepatitis C can be treated with a combination of pegylated interferon alfa and ribavirin. Since many users experience side effects, there are substantial limitatio...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/454A61K31/4184
CPCA61K31/454A61K31/498A61K38/12A61P31/14A61K2300/00A61K31/4985A61K31/7072
Inventor C.科林斯B.付A.古拉蒂J.科特M.科斯罗斯基Y.雷C-W.林R.刘F.门萨I.C.吴T.皮洛特-马蒂亚斯D.普加奇N.S.舒尔曼R.特林R.M.维亚尼S.王Z.张
Owner ABBVIE INC
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