13 Combination of the Ns5a Inhibitor, Gs-5885, the Ns3 Protease Inhibitor, Gs-9451, and Pegylated Interferon Plus Ribavirin in Treatment Experienced Patients With Genotype 1 Hepatitis C Infection

Everson, Gregory T.; Bisceglie, Adrian M. Di; Vierling, John M.; Hsieh, Fred H.; Trenkle, James D.; Kanwar, Bittoo; Subramanian, Mani; McHutchison, John G.; Ghalib, Reem; Rustgi, Vinod K.; Kwo, Paul Y.

doi:10.1016/s0168-8278(13)60015-x

Cited by 9 publications

(9 citation statements)

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“…For the remaining 3 studies that did include IFN as part of the treatment regimen, SVR24 rates were higher for patients with baseline NS5A RASs (37.5%‐75.8%). (Figure , Table ) . Overall, there was no difference in the SVR24 rate between GT1a and GT1b patients who harboured baseline NS5A RASs (GT1a, 53.5%; GT1b, 58.3%; Figure ).…”

Section: Resultsmentioning

confidence: 87%

“…Detailed descriptions of the 6 clinical trials (GS‐US‐248‐0120, GS‐US‐248‐0121, GS‐US‐248‐0131, GS‐US‐248‐0132, GS‐US‐256‐0124, and GS‐US‐256‐0148) have been published . Briefly, studies GS‐US‐248‐0120, GS‐US‐248‐0131 and GS‐US‐248‐0132 evaluated the all oral regimens of either 30 mg or 90 mg LDV once daily (QD) ± 200 mg QD of the NS3 protease inhibitor vedroprevir (VDV, GS‐9451) ± 30 mg twice daily (BID) of the non‐nucleoside NS5B polymerase inhibitor tegobuvir (TGV, GS‐9190) ± weight‐based ribavirin (RBV) BID.…”

Section: Methodsmentioning

confidence: 99%

“…Detailed descriptions of the 6 clinical trials (GS-US-248-0120, GS-US-248-0121, GS-US-248-0131, GS-US-248-0132, GS-US-256-0124, and GS-US-256-0148) have been published. [11][12][13][14][15][16] Briefly, studies GS-US-248-0120, GS-US-248-0131 and GS-US-248-0132 evaluated the all oral regimens of either 30 mg or 90 mg LDV once daily (QD) ± 200 mg QD of the NS3 protease inhibitor vedroprevir (VDV, GS-9451) ± 30 mg twice daily (BID) of the non-nucleoside NS5B polymerase inhibitor tegobuvir (TGV, GS-9190) ± weight-based ribavirin (RBV) BID . Studies GS-US-248-0121, GS-US-256-0124 and GS-US-256-0148 evaluated 30 mg LDV QD ± 200 mg VDV QD with weight-based RBV BID + pegylated interferon (IFN) once weekly.…”

Section: Study Populationmentioning

confidence: 99%

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Nonstructural protein 5A resistance profile in patients with chronic hepatitis C treated with ledipasvir‐containing regimens without sofosbuvir

Kitrinos

Corsa

Worth

et al. 2017

Journal of Viral Hepatitis

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The study aimed to evaluate the effects of baseline hepatitis C virus (HCV) nonstructural protein 5A (NS5A) resistance-associated substitutions (RASs) on sustained virologic response to ledipasvir (LDV)-containing regimens in the absence of sofosbuvir (SOF) in patients with HCV genotype (GT) 1 infection across 6 phase 2 clinical studies. We analysed data from 1103 patients who received either LDV + vedroprevir (NS3 protease inhibitor) + tegobuvir (NS5B inhibitor) ± ribavirin or LDV + ribavirin + pegylated interferon. Population sequencing of HCV NS5A was performed at baseline and at virologic failure from patient plasma samples. Of 1045 patients with available baseline sequences, 747 (67.7%) had GT1a, and 298 (26.9%) had GT1b infection. The overall prevalence of NS5A RASs at baseline was 9.4%; 7.6% (57/747) and 13.8% (41/298) of patients with GT1a and GT1b infection, respectively. The majority of GT1a-infected patients with NS5A RASs at baseline had a single NS5A RAS (78.9%) at NS5A positions K24R, M28T, Q30H/L, L31M and Y93H/N/C/S. The spectrum of NS5A RASs detected in GT1b patients was much less diverse compared to GT1a patients, with all patients harbouring a single NS5A RAS either L31M or Y93H/C. For patients treated with LDV-containing regimens in the absence of SOF, the presence of baseline NS5A RASs was associated with low SVR rates. In patients with virologic failure, nearly all had either pre-existing and/or emergent NS5A RASs: 287/287 (100%) and 40/42 (95.2%) patients with GT1a and GT1b infection, respectively. Three novel NS5A substitutions were identified as emergent NS5A RASs: K26E and S38F in GT1a; and L31I in GT1b. In conclusion, the presence of NS5A RASs at baseline reduced the SVR rate in patients treated with LDV in combination vedroprevir + tegobuvir ± ribavirin or ribavirin + pegylated interferon. Virologic failure was associated with the detection of NS5A RASs in nearly all patients. These results suggest that the resistance barrier may differ depending on HCV drug combination and may be more important than that of the individual DAAs.

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Section: Resultsmentioning

confidence: 87%

Section: Methodsmentioning

confidence: 99%

Section: Study Populationmentioning

confidence: 99%

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Nonstructural protein 5A resistance profile in patients with chronic hepatitis C treated with ledipasvir‐containing regimens without sofosbuvir

Kitrinos

Corsa

Worth

et al. 2017

Journal of Viral Hepatitis

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“…8 It is also being studied in combination with vedroprevir, ribavirin, and peginterferon for 6 to 24 weeks in both treatmentnaive and treatment-experienced adults infected with HCV genotype 1. 9,10 In 2013, approximately 3.2 million individuals in the United States were living with a chronic HCV infection, but only 1.8 million have been diagnosed. Of these patients, 1 to 1.2 million (32% to 38%) were referred for care and 220,000 to 360,000 (7% to 11%) were treated.…”

Section: Indicationsmentioning

confidence: 99%

Ledipasvir/Sofosbuvir

2015

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Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available on-line. Monographs can be customized to meet the needs of a facility. A drug class review is now published monthly with The Formulary Monograph Service. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, call The Formulary at 800-322-4349. The March 2015 monograph topics are paritaprevir, ritonavir, ombitasvir, and dasabuvir; meningococcal B bivalent recombinant vaccine; alemtuzumab; ceftolozane/tazobactam; and peramivir solution. The Safety MUE is on peramivir solution.

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“…A combination of ABT-450 (a NS3/4A protease inhibitor) boosted with ritonavir, ABT-267 (a NS5A inhibitor), ABT-333 (a non-nucleoside NS5B polymerase inhibitor) ± RBV has demonstrated SVR24 in >90 % of treatment naïve and experienced patients with HCV genotype 1 chronic infection; a phase III study in HIV-HCV coinfection is currently enrolling (NCT01939197) [84]. Ledipasvir is a NS5A inhibitor with evidence of increased SVR rates in combination with P/R in both treatment naïve and treatment experienced patients with HCV genotype 1 [85, 86]. Ledipasvir is now in phase III study in combination with sofosbuvir ± RBV as part of the ION studies which will include coinfected patients; this regimen is expected to be the first fixed dose DAA combination therapy for HCV genotype 1 [87, 88].…”

Section: Direct Acting Antivirals: the “How”mentioning

confidence: 99%

Treatment of Genotype 1 HCV Infection in the HIV Coinfected Patient in 2014

Chastain

Naggie

2013

Curr HIV/AIDS Rep

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Hepatitis C (HCV) coinfection is the leading cause of liver-related morbidity and is a leading cause of mortality in human immunodeficiency virus (HIV)-infected individuals in the antiretroviral therapy era. Direct-acting antiviral (DAA) therapies are transforming how HCV is treated with significant improvements in efficacy and tolerability. In this article, DAA agents expected to be available in 2014 are reviewed, including telaprevir, boceprevir, sofosbuvir, simeprevir, faldaprevir, and daclatasvir. Available data regarding clinical efficacy, adverse effects, and drug interactions in HIV-HCV coinfection are discussed. The management of adverse effects of HCV therapy and treatment considerations in patients with cirrhosis are also reviewed.

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13 Combination of the Ns5a Inhibitor, Gs-5885, the Ns3 Protease Inhibitor, Gs-9451, and Pegylated Interferon Plus Ribavirin in Treatment Experienced Patients With Genotype 1 Hepatitis C Infection

Cited by 9 publications

References 0 publications

Nonstructural protein 5A resistance profile in patients with chronic hepatitis C treated with ledipasvir‐containing regimens without sofosbuvir

Nonstructural protein 5A resistance profile in patients with chronic hepatitis C treated with ledipasvir‐containing regimens without sofosbuvir

Ledipasvir/Sofosbuvir

Treatment of Genotype 1 HCV Infection in the HIV Coinfected Patient in 2014

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