Multitargeted drug combination promising when new HCV antivirals fail

SAN FRANCISCO – A five-drug regimen of direct-acting antiviral agents with diverse targets appears to be highly effective as a retreatment in patients infected with the hepatitis C virus patients who had virologic failure on a first-line direct-acting antiviral (DAA) regimen, according to results of a small study presented as a late-breaker at the annual meeting of the American Association for the Study of Liver Diseases (AASLD).

“Retreatment options for [hepatitis C virus (HCV)–infected] patients who fail treatment with DAA regimens are not yet clearly defined,” reported Dr. Fred Poordad, Texas Liver Institute, University of Texas Health Science Center, San Antonio. The five-drug regimen in this study was characterized as “promising.”

The study enrolled patients with genotype (GT) 1 infection who had virologic failure on a previous DAA treatment regimen. All were treated with ombitasvir with ritonavir-boosted paritaprevir (OBV/PTV/r) plus dasabuvir (DSV) and sofosbuvir (SOF). Those with GT1a infection and cirrhosis also received ribavirin and were treated for 24 weeks. All others were treated for 12 weeks.

Twenty-two patients were enrolled. The primary endpoint was sustained virologic response (SVR), defined as HCV RNA level below 25 IU/mL at 4 weeks after completion of the antiviral regimen. The DAA regimens on which patients had previously failed included OBV/PTV/r plus DSV in 14 patients, OBV/PTV/r in 2 patients, telaprevir in 2 patients, SOF in 2 patients, and a simeprevir-based regimen in 2 patients.

Fourteen of 15 (97%) patients treated for 12 weeks achieved SVR12. Of the seven patients treated for 24 weeks, all had HCV suppressed below the limit of detection while on therapy. The SVR4 rate is 100%, with final SVR results pending.

Neither of the two serious side effects – pneumonia and cellulitis – were considered to be drug related, but the patient who developed pneumonia discontinued the study regimen at week 10 without virologic failure.

Virologic failure to DAAs that inhibit NS5A, a protein important to virus assembly, is often associated with resistance-associated variants in genes that code for this protein. According to Dr. Poordad, these variants “have been shown to persist up to 96 weeks posttreatment.” As a result, patients who fail a first-line DAA “are likely to require a multitargeted approach to retreat infection.”

Although this study is small, the very high SVR rates support this premise.

Dr. Poordad reported financial relationships with Abbott/AbbVie, Achillion, Bristol-Myers Squibb, Boehringer Ingelheim, Genentech, Gilead, Inhibitex, Idenix, Janssen, Merck, Novartis, Pfizer, Pharmasset, Salix, Tibotec/Janssen, and Vertex.

SAN FRANCISCO – A five-drug regimen of direct-acting antiviral agents with diverse targets appears to be highly effective as a retreatment in patients infected with the hepatitis C virus patients who had virologic failure on a first-line direct-acting antiviral (DAA) regimen, according to results of a small study presented as a late-breaker at the annual meeting of the American Association for the Study of Liver Diseases (AASLD).

“Retreatment options for [hepatitis C virus (HCV)–infected] patients who fail treatment with DAA regimens are not yet clearly defined,” reported Dr. Fred Poordad, Texas Liver Institute, University of Texas Health Science Center, San Antonio. The five-drug regimen in this study was characterized as “promising.”

The study enrolled patients with genotype (GT) 1 infection who had virologic failure on a previous DAA treatment regimen. All were treated with ombitasvir with ritonavir-boosted paritaprevir (OBV/PTV/r) plus dasabuvir (DSV) and sofosbuvir (SOF). Those with GT1a infection and cirrhosis also received ribavirin and were treated for 24 weeks. All others were treated for 12 weeks.

Twenty-two patients were enrolled. The primary endpoint was sustained virologic response (SVR), defined as HCV RNA level below 25 IU/mL at 4 weeks after completion of the antiviral regimen. The DAA regimens on which patients had previously failed included OBV/PTV/r plus DSV in 14 patients, OBV/PTV/r in 2 patients, telaprevir in 2 patients, SOF in 2 patients, and a simeprevir-based regimen in 2 patients.

Fourteen of 15 (97%) patients treated for 12 weeks achieved SVR12. Of the seven patients treated for 24 weeks, all had HCV suppressed below the limit of detection while on therapy. The SVR4 rate is 100%, with final SVR results pending.

Neither of the two serious side effects – pneumonia and cellulitis – were considered to be drug related, but the patient who developed pneumonia discontinued the study regimen at week 10 without virologic failure.

Virologic failure to DAAs that inhibit NS5A, a protein important to virus assembly, is often associated with resistance-associated variants in genes that code for this protein. According to Dr. Poordad, these variants “have been shown to persist up to 96 weeks posttreatment.” As a result, patients who fail a first-line DAA “are likely to require a multitargeted approach to retreat infection.”

Although this study is small, the very high SVR rates support this premise.

Dr. Poordad reported financial relationships with Abbott/AbbVie, Achillion, Bristol-Myers Squibb, Boehringer Ingelheim, Genentech, Gilead, Inhibitex, Idenix, Janssen, Merck, Novartis, Pfizer, Pharmasset, Salix, Tibotec/Janssen, and Vertex.

SAN FRANCISCO – A five-drug regimen of direct-acting antiviral agents with diverse targets appears to be highly effective as a retreatment in patients infected with the hepatitis C virus patients who had virologic failure on a first-line direct-acting antiviral (DAA) regimen, according to results of a small study presented as a late-breaker at the annual meeting of the American Association for the Study of Liver Diseases (AASLD).

“Retreatment options for [hepatitis C virus (HCV)–infected] patients who fail treatment with DAA regimens are not yet clearly defined,” reported Dr. Fred Poordad, Texas Liver Institute, University of Texas Health Science Center, San Antonio. The five-drug regimen in this study was characterized as “promising.”

The study enrolled patients with genotype (GT) 1 infection who had virologic failure on a previous DAA treatment regimen. All were treated with ombitasvir with ritonavir-boosted paritaprevir (OBV/PTV/r) plus dasabuvir (DSV) and sofosbuvir (SOF). Those with GT1a infection and cirrhosis also received ribavirin and were treated for 24 weeks. All others were treated for 12 weeks.

Twenty-two patients were enrolled. The primary endpoint was sustained virologic response (SVR), defined as HCV RNA level below 25 IU/mL at 4 weeks after completion of the antiviral regimen. The DAA regimens on which patients had previously failed included OBV/PTV/r plus DSV in 14 patients, OBV/PTV/r in 2 patients, telaprevir in 2 patients, SOF in 2 patients, and a simeprevir-based regimen in 2 patients.

Fourteen of 15 (97%) patients treated for 12 weeks achieved SVR12. Of the seven patients treated for 24 weeks, all had HCV suppressed below the limit of detection while on therapy. The SVR4 rate is 100%, with final SVR results pending.

Neither of the two serious side effects – pneumonia and cellulitis – were considered to be drug related, but the patient who developed pneumonia discontinued the study regimen at week 10 without virologic failure.

Virologic failure to DAAs that inhibit NS5A, a protein important to virus assembly, is often associated with resistance-associated variants in genes that code for this protein. According to Dr. Poordad, these variants “have been shown to persist up to 96 weeks posttreatment.” As a result, patients who fail a first-line DAA “are likely to require a multitargeted approach to retreat infection.”

Although this study is small, the very high SVR rates support this premise.

Dr. Poordad reported financial relationships with Abbott/AbbVie, Achillion, Bristol-Myers Squibb, Boehringer Ingelheim, Genentech, Gilead, Inhibitex, Idenix, Janssen, Merck, Novartis, Pfizer, Pharmasset, Salix, Tibotec/Janssen, and Vertex.