METHOD OF TREATING HEPATITIS C PATIENTS
This application discloses a novel method of identifying patients amongst treatment naïve patients suffering from HCV infection that are amenable to treatment with a protease inhibitor. The application also discloses a method of treating treatment naïve, nonresponder and relapsed patients suffering from an HCV infection.
1 - 34 . (canceled)
35 . A method of treating patients suffering from hepatitis C infection, said patients selected from patients that are treatment naïve and patients that have relapsed from having a negative HCV status, the method comprising: (a) administering a combination of at least one antiviral compound and an interferon for a lead-in period; (b) at the end of said lead-in period administering a combination of at least one antiviral compound, an interferon, and at least one HCV protease inhibitor compound for a second treatment period of sufficient duration to achieve a non-detectable viral load using HCV-RNA assay.
36 . The method of claim 35 , wherein the combination of the antiviral compound and the interferon administered during the lead-in period comprises ribavirin and pegylated interferon alfa.
37 . The method of claim 35 , wherein the HCV protease inhibitor compound is selected from any of the HCV protease inhibiting compounds described either in published international application no. WO 2007/092616 or in published international application no. WO 2002/18369.
38 . The method of claim 35 wherein the HCV protease inhibitor compound is selected from compounds having the formula:
39 . The method of claim 38 , wherein the interferon is peginterferon alfa-2b.
40 . The method of claim 38 , wherein the HCV protease inhibitor is coadministered with a CYP-3A4 inhibitor.
41 . The method of claim 40 , wherein the CYP-3A4 inhibitor is ritonavir.
42 . The method of claim 35 , wherein the lead-in period has a duration of from about 2 weeks to about 17 weeks.
43 . The method of claim 35 , wherein the lead-in period is four weeks.
44 . The method of claim 43 , wherein the second treatment period has a duration of from about 12 weeks to about 28 weeks.
45 . The method of 35 , wherein the amount of interferon administered to patients during any of the time periods in which an interferon is administered is from about 0.5 microgram/Kg of patient weight to about 1.5 microgram/Kg of patient weight.
46 . The method of claim 45 , wherein the amount of antiviral compound administered to a patient during any of the time periods in which an antiviral compound is administered is from about 10 mg/Kg of patient weight to about 20 mg/Kg of patient weight.
47 . The method of claim 46 , wherein the protease inhibitor compound is the compound of Formula Ia (boceprevir) and the amount administered to a patient during any of the periods in which a protease inhibitor is administered is about 800 mg at intervals of from about 7 hours to about 9 hours during the treatment period in which it is administered.
48 . The method of claim 38 , wherein the antiviral is ribavirin.
49 . The method of claim 48 , wherein the interferon is peginterferon alfa-2b.
50 . The method of claim 48 , wherein the HCV protease inhibitor is coadministered with a CYP-3A4 inhibitor.
51 . The method of claim 50 , wherein the interferon is peginterferon alfa-2b and the CYP-3A4 inhibitor is ritonavir.
52 . The method of claim 42 , wherein the lead-in period is from about 16 to about 17 weeks.
53 . The method of claim 42 , wherein the lead-in period is from about 12 to about 17 weeks.
54 . The method of claim 42 , wherein the lead-in period is up to 16 weeks.
55 . The method of claim 43 , wherein the total treatment time is 28 weeks.
56 . A method of identifying among a group of treatment naïve and relapsed patients suffering from hepatitis C infection, patients who may be successfully managed to an SVR status comprising: administering a combination of at least one antiviral compound and an interferon for a lead-in period; and selecting the patients showing a 2 log or greater drop in viral load to receive a combination of at least one antiviral compound, an interferon, and at least one HCV protease inhibitor for a second treatment period of sufficient duration to achieve a sustained viral response (SVR).
57 . The method of claim 56 , wherein the combination of the antiviral compound and the interferon administered during the lead-in period comprises ribavirin and pegylated interferon alfa.
58 . The method of claim 57 , wherein the HCV protease inhibitor is selected from any of the HCV protease inhibiting compounds described either in published international application no. WO 2007/092616 or in published international application no. WO 2002/18369.
59 . The method of claim 56 wherein the HCV protease inhibitor is selected from compounds having the formula:
60 . The method of claim 59 , wherein the interferon is peginterferon alfa-2b.
61 . The method of claim 59 , wherein the HCV protease inhibitor is coadministered with a CYP-3A4 inhibitor.
62 . The method of claim 61 , wherein the CYP-3A4 inhibitor is ritonavir.
63 . The method of claim 59 , wherein the lead-in period has a duration of from about 2 weeks to about 17 weeks.
64 . The method of claim 59 , wherein the lead-in period is four weeks.
65 . The method of claim 64 , wherein the second treatment period has a duration of from about 12 weeks to about 28 weeks.
66 . The method of claim 59 , wherein the amount of interferon administered to patients during any of the time periods in which an interferon is administered is from about 0.5 microgram/Kg of patient weight to about 1.5 microgram/Kg of patient weight.
67 . The method of claim 66 , wherein the amount of antiviral compound administered to a patient during any of the time periods in which an antiviral compound is administered is from about 10 mg/Kg of patient weight to about 20 mg/Kg of patient weight.
68 . The method of claim 67 , wherein the protease inhibitor administered is the compound of Formula Ia (boceprevir) and the amount administered to a patient during any of the periods in which a protease inhibitor is administered is about 800 mg at intervals of from about 7 hours to about 9 hours during the treatment period in which it is administered.
69 . The method of claim 59 , wherein the antiviral is ribavirin.
70 . The method of claim 69 , wherein the interferon is peginterferon alfa-2b.
71 . The method of claim 69 , wherein the HCV protease inhibitor is coadministered with a CYP-3A4 inhibitor.
72 . The method of claim 71 , wherein the CYP-3A4 inhibitor is ritonavir and is peginterferon alfa-2b.
73 . The method of claim 63 wherein the lead-in period is from about 16 to about 17 weeks.
74 . The method of claim 63 wherein the lead-in period is from about 12 to about 17 weeks.
75 . The method of claim 63 wherein the lead-in period is up to 16 weeks.
76 . The method of claim 64 , wherein the total treatment time is 28 weeks.
77 . A method of treating a patient suffering from hepatitis C infection, comprising: (a) administering to the patient a combination of at least one antiviral compound and an interferon for a lead-in period; and (b) at the end of said lead-in period administering a combination of at least one antiviral compound, an interferon, and at least one HCV protease inhibitor compound for a second treatment period of sufficient duration to achieve a sustained viral response (SVR).
78 . The method of claim 77 , wherein the HCV protease inhibitor is selected from compounds having the formula:
79 . The method of claim 78 , wherein the antiviral compound is ribavirin.
80 . The method of claim 79 , wherein the patient is treatment naïve.
81 . The method of claim 80 , wherein the patient is infected with genotype 1 HCV.
82 . The method of claim 81 , wherein the lead-in period is four weeks.
83 . The method of claim 82 , wherein the total treatment time is 28 weeks.
84 . The method of claim 83 , wherein the interferon is pegylated interferon alfa 2a or pegylated interferon alfa 2b.
85 . The method of claim 79 , wherein the patient is a non-responder to previous treatment with an interferon alfa and ribavirin, is infected with genotype 1 HCV, the interferon is pegylated interferon alfa 2a or pegylated interferon alfa 2b, the lead-in period is four weeks, and the total treatment time is 28 weeks.
86 . The method of claim 79 , wherein the patient relapsed after previous treatment with an interferon alfa and ribavirin, is infected with genotype 1 HCV, the interferon is pegylated interferon alfa 2a or pegylated interferon alfa 2b, the lead-in period is four weeks, and the total treatment time is 28 weeks.
87 . The method of claim 77 , wherein the patient is treatment naïve, is infected with genotype 1, the interferon is peginterferon alfa-2b, the antiviral compound is ribavirin, the lead-in period is four weeks and the protease inhibitor is boceprevir.
88 . The method of claim 77 , wherein the patient is a nonresponder to previous treatment with an interferon alfa and ribavirin, the interferon is pegylated interferon alfa 2a or pegylated interferon alfa 2b, the antiviral compound is ribavirin, and the lead-in period is four weeks.
89 . The method of claim 88 , wherein the interferon is peginterferon alfa-2b and the protease inhibitor is boceprevir.
90 . A method of treating a patient suffering from hepatitis C infection, comprising: (a) administering to the patient a combination of at least one antiviral compound and an interferon for a lead-in period; and (b) if the patient has at least a 2 log drop in viral RNA at the end of the lead-in period, then administering a combination of the antiviral compound, the interferon, and the HCV protease inhibitor compound for a second treatment period of sufficient duration to achieve a sustained viral response (SVR).
91 . The method of claim 90 , wherein the HCV protease inhibitor is selected from compounds having the formula:
92 . The method of claim 91 , wherein the antiviral compound is ribavirin.
93 . The method of claim 92 , wherein the patient is treatment naïve and infected with genotype 1 HCV.
94 . The method of claim 93 , wherein the lead-in period is four weeks.
95 . The method of claim 94 , wherein the total treatment time is 28 weeks.
96 . The method of claim 95 , wherein the interferon is pegylated interferon alfa 2a or pegylated interferon alfa 2b.
97 . The method of claim 92 , wherein the patient is a non-responder to previous treatment with an interferon alfa and ribavirin, is infected with genotype 1 HCV, the interferon is pegylated interferon alfa 2a or pegylated interferon alfa 2b, the lead-in period is four weeks, and the total treatment time is 28 weeks.
98 . The method of claim 92 , wherein the patient relapsed after previous treatment with an interferon alfa and ribavirin, is infected with genotype 1 HCV, the interferon is pegylated interferon alfa 2a or pegylated interferon alfa 2b, the lead-in period is four weeks, and the total treatment time is 28 weeks.
99 . The method of claim 91 , wherein the patient is treatment naïve, is infected with genotype 1, the interferon is peginterferon alfa-2b, the antiviral compound is ribavirin, the protease inhibitor is boceprevir and the lead-in period is four weeks.