Asunaprevir, a protease inhibitor for the treatment of hepatitis C infection

Figures & data

Table 1 Trials that have evaluated asunaprevir in combination with other drugs

Reference	Number of patients, genotype, type of patients	Stage of disease	Arms	Duration of therapy	Sustained virological response
Bronowicki et al^Citation74	47, genotype 1, naïve	Noncirrhotic	1) PR + ASN (200 mg twice daily) 2) PR + ASN (600 mg twice daily) 3) PR + ASN (600 mg once daily) 4) PR + placebo	48 weeks	1) 83% 2) 83% 3) 92% 4) 46%
Bronowicki et al^Citation75	238, genotype 1 (89%) and 4(11%), naïve	Data not available	1) PR + ASN (200 mg twice daily) 2) PR + placebo	1) After 12 weeks, subjects who achieved a PDR* were randomized to continue i) PR + ASN or ii) PR + placebo for further 12 weeks; subjects who failed to achieve a PDR* received further 36 weeks of PR 2) 48 weeks	1) 64% for genotype 1 subjects; 90% for genotype 4 subjects 2) 45% for genotype 1 subjects; 43% for genotype 4 subjects
Vierling et al^Citation76	119, genotype 1, naïve	Noncirrhotic	1) Interferon lambda-1 a + RBV + DCV 2) Interferon lambda-1 a + RBV + ASN 200 mg twice daily 3) PR + placebo	1–2) Achievement of PDR:† 24 weeks; no achievement of PDR: 24 weeks of triple + further 24 weeks of interferon lambda-1a plus RBV 3) 48 weeks	SVR12 1) 76% 2) 75% 3) NA
Lok et al^Citation77	21, genotype 1 (86% subtype 1a), nonresponder	Noncirrhotic	1) DCV + ASN 600 mg twice daily 2) DCV + ASN 600 mg twice daily + PR	24 weeks	1) 36% 2) 90%
Lok et al^Citation78	101, genotype 1 (53% subtype 1a, 47% subtype 1b), null responders	Noncirrhotic	Subtype 1a: B1) DCV + ASN (200 mg twice daily) + PR B2) DCV + ASN (200 mg once daily) + PR B3) DCV + ASN (200 mg once daily) + RBV Subtype 1b: A1) DCV + ASN (200 mg twice daily) A2) DCV + ASN (200 mg once daily) B1) DCV + ASN (200 mg twice daily) + PR B2) DCV + ASN (200 mg once daily) + PR B3) DCV + ASN (200 mg once daily) + RBV	24 weeks	A1) 83% A2) 60% B1) 90% (88% for subtype 1a and 100% for subtype 1b) B2) 95% (95% for subtype la and 100% for subtype 1b) B3) ≠23% (5.6% for subtype 1a and 100% for subtype 1b)
Suzuki et al^Citation79	43, subtype 1b, (21 null responders and 22 intolerant/ineligible to PR)	Noncirrhotic	DCV + ASN (200 mg twice daily)	24 weeks	76.7% (90.5% in null responders and 63.6% in intolerant/ineligible subjects)
Kumada et al^Citation80	222 subtype 1b, 135 ineligible/intolerant to interferon and 87 nonresponders to PR	Cirrhotic (22 patients) and noncirrhotic (200 patients)	DCV + ASN (100 mg twice daily)	24 weeks	84.7% (87.4% in ineligible/intolerant and 80.5% in nonresponders)
Manns et al,^Citation81 HALLMARK-DUAL	745, subtype 1b (305 naïve, 205 experienced, 235 interferon ineligible/intolerant)	Both cirrhotic and noncirrhotic (16% of the naïve, 31 % of the nonresponder, and 47% of the ineligible/intolerant were cirrhotic)	DCV + ASN (100 mg twice daily)	24 weeks	SVR12 90% naïve 82% nonresponder 82% ineligible/intolerant
Everson et al^Citation82	66, genotype 1, naïve	Noncirrhotic	1 e 2) DCV + ASN (200 mg twice daily) + and BMS-791325 (75 mg twice daily) 3 e 4) DCV + ASN (200 mg twice daily) + and BMS-791325 (150 mg twice daily)	1) 24 weeks 2) 12 weeks 3) 24 weeks 4) 12 weeks	SVR12 1) 94% 2) 94% 3) 94% 4) 89%
Everson et al^Citation83	166, genotype 1, naïve		1) DCV‡ + ASN (200 mg twice daily) + BMS-791325 (75 mg twice daily) 2) DCV‡ + ASN (200 mg twice daily) + BMS-791325 150 mg twice daily)	12 weeks	SVR12 1) 88.8% 2) 89.5%

Notes:

* PDR, protocol defined response, ie, HCV RNA <25 IU/mL at week 4 and undetectable at week 10

† PDR, protocol defined response, ie, week 4 HCV RNA <25 IU/mL, week 12 undetectable

≠ SVR4

‡ administered at a dose of 30 mg twice daily; PR was administered at standard doses; interferon-lambda la was administered at 180 μg weekly; daclatasvir was administered at 60 mg once daily.

Abbreviations: ASN, asunaprevir; PR, PEGylated-interferon + ribavirin; RBV, ribavirin; DCV, daclatasvir; NA, not available; SVR, sustained virological response.

BronowickiJPPolSThuluvathPJRandomized study of asunaprevir plus pegylated interferon-alpha and ribavirin for previously untreated genotype 1 chronic hepatitis CAntivir Ther201318788589323804631

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BronowickiJPRatziuVGadanoAAsunaprevir with Peginterferon-alfa and ribavirin in treatment-naive patients with genotype-1 or-4 chronic hepatitis C: SVR24 results from a randomized phase 2b study (AI447016)J Hepatol201358S571S572

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VierlingJMLatailladeMGaneEJSustained virologic response (SVR12) in HCV genotype 1 patients receiving peginterferon lambda in combination with ribavirin and either daclatasvir or asunaprevir: interim results from the D-LITE studyHepatology201256615221523

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LokASGardinerDFLawitzEPreliminary study of two antiviral agents for hepatitis C genotype 1N Engl J Med2012366321622422256805

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LokASGardinerDFHezodeCRandomized trial of daclatasvir and asunaprevir with or without PegIFN/RBV for hepatitis C virus genotype 1 null respondersJ Hepatol201460349049924444658

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SuzukiYIkedaKSuzukiFDual oral therapy with daclatasvir and asunaprevir for patients with HCV genotype 1b infection and limited treatment optionsJ Hepatol201358465566223183526

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KumadaHSuzukiYIkedaKDaclatasvir plus asunaprevir for chronic HCV genotype 1b infectionHepatology20145962083209124604476

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MannsMPolSJacobsonIAll-oral dual therapy with daclatasvir and asunaprevir in patients with HCV genotype 1B infection: phase 3 study resultsJ Hepatol2014601S524S525

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EversonGTSimsKDRodriguez-TorresMEfficacy of an interferon- and ribavirin-free regimen of daclatasvir, asunaprevir, and BMS-791325 in treatment-naive patients with HCV genotype 1 infectionGastroenterology2014146242042924184132

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EversonGTSimsKDThuluvathPJPhase 2b study of the interferon-free and ribavirin-free combination of daclatasvir, asunaprevir, and BMS-791325 for 12 weeks in treatment-naive patients with chronic HCV genotype 1 infectionHepatology20135861377A

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