Treatment of HCV infected patients with cirrhosis
Inventors
Sommadossi, Jean-Pierre • Moussa, Adel • Pietropaolo, Keith M. • Zhou, Xiao-Jian
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11690860-B2
Publication Date
2023-07-04
Expiration Date
Abstract
A pharmaceutical composition that includes a compound of the structure: to treat an HCV infected patient with cirrhosis, and uses thereof.
Core Innovation
The disclosed invention relates to a hepatitis C treatment strategy that uses a compound provided as the hemi-sulfate salt of Compound 2, an NS5B RNA-dependent RNA polymerase inhibitor. The method is directed to a hepatitis C-infected human with decompensated cirrhosis, including compensated and decompensated disease defined by Child-Pugh A, Child-Pugh B, and Child-Pugh C.
The disclosure reports clinical safety and tolerability findings and describes pharmacokinetic and pharmacodynamic observations after dosing. It states that there are no serious adverse events and no liver injury findings, and it describes early and potent HCV RNA reductions across cirrhotic and HCV genotype populations, including GT1, GT2, and GT3.
The disclosure further characterizes exposure and viral-load effects in relation to NS5B inhibition. It states that steady-state metabolite 1-7 trough levels exceed EC95 and that modeling predicts a viral load reduction of at least 4 log after 7 days for a 600 mg/day Compound 2 regimen, with metabolism to an active triphosphate and the metabolite 1-7 used as a plasma surrogate.
The disclosure also describes formulation and compound form aspects, including hemi-sulfate and alternative salt forms for the compound, and it includes genotypic coverage with particular emphasis on GT3 cirrhotics. It states dosing-duration ranges and the metabolic pathway in terms of triphosphate prodrug activation, surrogated by measurable metabolite 1-7 in plasma.
Claims Coverage
The provided independent claim defines a treatment method for hepatitis C-infected humans with decompensated cirrhosis by providing an effective amount of a compound of a specified formula, optionally in a pharmaceutically acceptable carrier. The claim set includes one independent claim and multiple dependent claims that add inventive feature constraints to the base treatment.
Treatment of decompensated cirrhosis hepatitis C by providing an effective amount of a specified formula compound
A method to treat a hepatitis C-infected human with decompensated cirrhosis comprising providing an effective amount of a compound of the formula optionally in a pharmaceutically acceptable carrier.
Within the provided claim set, the main inventive coverage is the use of a specified formula compound, optionally formulated in a pharmaceutically acceptable carrier, to treat hepatitis C-infected humans with decompensated cirrhosis, with dependent claims further narrowing the treated population and administration parameters.
Stated Advantages
No serious adverse events.
No liver injury findings.
Early and potent HCV RNA reductions after dosing.
Steady-state metabolite 1-7 trough levels exceed EC95.
Modeling predicts at least 4 log viral load reduction after 7 days for the stated regimen equivalence.
Documented Applications
Treating a hepatitis C-infected human with decompensated cirrhosis, including compensated and decompensated disease defined by Child-Pugh A, Child-Pugh B, and Child-Pugh C, using the hemi-sulfate salt of Compound 2 as an NS5B inhibitor.
Treatment reported for cirrhotic patients with HCV genotypes including GT1, GT2, and GT3, with emphasis on GT3 cirrhotics and specific GT1a/GT1b and GT3a/GT3b genotypes in the disclosure context.
Interested in licensing this patent?