US 20140275099A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2014/0275099 A1 Bernstein et al. (43) Pub. Date: Sep. 18, 2014 (54) METHODS FOR TREATING HCV Publication Classification (71) Applicant: AbbVie Inc., North Chicago, IL (US) (51) Int. Cl. A613 L/4985 (2006.01) (72) Inventors: Barry M. Bernstein, Mequon, WI (US); A613 L/454 (2006.01) Sandeep Dutta, Lincolnshire, IL (US); (52) U.S. Cl. Wei Liu, Mundelein, IL (US); Thomas CPC ........... A6 IK3I/4985 (2013.01); A61 K3I/454 J. Podsadecki, Chicago, IL (US); (2013.01) Andrew L. Campbell, Lake Forest, IL USPC .......................................................... S14/250 (US); Rajeev M. Menon, Buffalo Grove, IL (US); Chih-Wei Lin, Vernon Hills, IL (57) ABSTRACT (US); Tianli Wang, Lake Bluff, IL (US); The present invention features interferon- and ribavirin-free Walid M.Awni, Green Oaks, IL (US) therapies for the treatment of HCV. Preferably, the treatment is over a shorter duration of treatment, such as no more than (21) Appl. No.: 14/210,870 12 weeks. In one aspect, the treatment comprises administer ing at least two direct acting antiviral agents without inter (22) Filed: Mar 14, 2014 feron and ribavirin to a subject with HCV infection, wherein the treatment lasts for 12 weeks, and said at least two direct Related U.S. Application Data acting antiviral agents comprise (a) Compound 1 or a phar (60) Provisional application No. 61/783,376, filed on Mar. maceutically acceptable salt thereofand (b) Compound 2 or a 14, 2013. pharmaceutically acceptable salt thereof. 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This application claims the benefit of U.S. Provi acceptable salt thereof, and (b) Compound 2 or a pharmaceu sional Application No. 61/783,376, filed Mar. 14, 2013, tically acceptable salt thereof. The at least two DAAs can also which is incorporated herein by reference in its entirety. optionally comprise another anti-HCV agent. The other optional anti-HCV agent can be selected from protease FIELD OF THE INVENTION inhibitors, nucleoside or nucleotide polymerase inhibitors, non-nucleoside polymerase inhibitors, NS3B inhibitors, 0002 The present invention relates to interferon-free and NS4A inhibitors, NS5A inhibitors, NS5B inhibitors, cyclo ribavirin-free treatment for hepatitis C virus (HCV). philin inhibitors, or combinations thereof. For example, in some embodiments, the DAAs used in a method of the present BACKGROUND OF THE INVENTION invention comprise or consist of (a) Compound 1 or a phar 0003. The HCV is an RNA virus belonging to the Hepa maceutically acceptable salt thereof, and (b) Compound 2 or civirus genus in the Flaviviridae family. The enveloped HCV a pharmaceutically acceptable salt thereof. For another virion contains a positive stranded RNA genome encoding all example, the DAAs used in a method of the present invention known virus-specific proteins in a single, uninterrupted, open comprise or consist of (a) Compound 1 or a pharmaceutically reading frame. The open reading frame comprises approxi acceptable salt thereof, (b) Compound 2 or a pharmaceuti mately 9500 nucleotides and encodes a single large polypro cally acceptable salt thereof, and (c) a HCV polymerase tein of about 3000 amino acids. The polyprotein comprises a inhibitor, wherein said HCV polymerase inhibitor can be a core protein, envelope proteins E1 and E2, a membrane nucleotide or nucleoside polymerase inhibitor or a non bound protein p7, and the non-structural proteins NS2. NS3, nucleoside or non-nucleotide polymerase inhibitor. NS4A, NS4B, NS5A and NS5B. 0008. Non-limiting examples of the other optional antic 0004 Chronic HCV infection is associated with progres HCV agent include PSI-7977 (sofosbuvir), PSI-938, BMS sive liver pathology, including cirrhosis and hepatocellular 790052 (daclatasvir), BMS-650032 (asunaprevir), BMS carcinoma. Chronic hepatitis C may be treated with peginter 791325, GS-5885 (ledipasvir), GS-9451 (tegobuvir), feron-alpha in combination with ribavirin. Substantial limi GS-9190, GS-9256, BI-201335. BI-27127, telaprevir, tations to efficacy and tolerability remain as many users Suffer VX-222, TMC-435 (simepravir), MK-5172, MK-7009 (vani from side effects, and viral elimination from the body is often previr), danoprevir, R7128 (mericitabine), and any combina incomplete. Therefore, there is a need for new therapies to tion thereof. treat HCV infection. 0009. In any method described herein, the DAAS can be administered in any effective dosing schemes and/or frequen BRIEF SUMMARY OF THE INVENTION cies; for example, they can each be administered daily. Each DAA can be administered either separately or in combina 0005 One aspect of the present invention features meth tion, and each DAA can be administered once a day, twice a ods for treating HCV infection in a subject in need of such day, or three times a day. Preferably, Compound 1 (or a treatment. The methods comprise administering at least two pharmaceutically acceptable salt thereof) and Compound 2 direct acting antiviral agents (DAAS) to the Subject for a (or a pharmaceutically acceptable salt thereof) are adminis duration of no more than 12 weeks, or for another duration as tered once daily. set forth herein. The at least two DAAs comprise Compound 0010 Preferably, Compound 1 (or a pharmaceutically 1 (or a pharmaceutically acceptable salt thereof) and Com acceptable salt thereof) is administered from 100 mg to 600 pound 2 (or a pharmaceutically acceptable salt thereof). Pref mg once daily, and Compound 2 (or a pharmaceutically erably, the duration of the treatment is 12 weeks. The duration acceptable salt thereof) is administered from 50 to 500 mg of the treatment can also be, for example, no more than 8 once daily. More preferably, Compound 1 (or a pharmaceu weeks. Preferably, the two or more DAAs are administered in tically acceptable salt thereof) is administered from 200 mg to amounts effective to provide a Sustained Virological response 600 mg once daily, and Compound 2 (or a pharmaceutically (SVR) or achieve another desired measure of effectiveness in acceptable salt thereof) is administered from 100 to 500 mg the subject. The subject is not administered ribavirin during once daily. Highly preferably, Compound 1 (or a pharmaceu the treatment regimen. The Subject is also not administered tically acceptable salt thereof) is administered from 400 mg to interferon during the treatment regimen. Put another way, the 600 mg once daily, and Compound 2 (or a pharmaceutically methods exclude the administration of interferon or ribavirin acceptable salt thereof) is administered from 100 to 500 mg to the subject, thereby avoiding the side effects associated once daily. For instance, Compound 1 (or a pharmaceutically with interferon and ribavirin. acceptable salt thereof) can be administered 400 mg once 0006 Another aspect of the present invention features daily, and Compound 2 (or a pharmaceutically acceptable salt methods for treating a population of subjects having HCV thereof) is administered 120 mg once daily. For another infection. The methods comprise administering at least two instance, Compound 1 (or a pharmaceutically acceptable salt DAAS to the subjects for a duration of no more than 12 weeks. thereof) can be administered 400 mg once daily, and Com The at least two DAAS comprise Compound 1 (or a pharma pound 2 (or a pharmaceutically acceptable salt thereof) can be ceutically acceptable salt thereof) and Compound 2 (or a administered 240 mg once daily. pharmaceutically acceptable salt thereof). Preferably, the at 0011. In yet another aspect, the present invention features least two DAAS are administered to the Subjects in amounts a combination of Compound 1 (or a pharmaceutically accept effective to result in SVR or another measure of effectiveness able Salt thereof) and Compound 2 (or a pharmaceutically in at least about 70% of the population, preferably at least acceptable salt thereof) for use to treat HCV infection. The about 80% of the population, or more preferably at least about treatment comprises administering the DAAS to a subject 90%/o of the population. infected with HCV. The duration of the treatment regimen is US 2014/0275099 A1 Sep. 18, 2014 no more than twelve weeks (e.g., the duration being 12 a null responder) infected with HCV genotype 1. In yet weeks; or the duration being 11, 10, 9, 8, 7, 6, 5, 4, or 3 another example, the treatment lasts for 8 weeks, and the weeks). Preferably, the duration of the treatment regimen is Subject being treated is a non-responder (e.g., a null twelve weeks. The duration of the treatment can also last, for responder) infected with HCV genotype 1. In yet another example, no more than eight weeks (e.g., the duration being 8 example, the treatment lasts for 12 weeks, and the Subject being treated is a non-responder (e.g., a null responder) weeks; or the duration being 7, 6, 5, 4, or 3 weeks).