In the Journals

Zepatier effective for HCV genotype 3 regardless of experience, resistance

Zepatier demonstrated high efficacy among patients with hepatitis C genotype 3, regardless of treatment experience or baseline resistance-associated substitutions, according to recently published data.

“People with HCV [genotype 3] infection and cirrhosis who have failed previous treatment attempts are generally regarded as one of the most difficult-to-treat populations with HCV infection,” Graham R. Foster, MD, from the Queen Mary University, London, and colleagues wrote. “Additional treatment options are therefore required for this population, and increasing the barrier to resistance through the introduction of a third mechanistically distinct antiviral agent represents a rational solution to overcoming resistance-associated failure.”

In a phase 2 clinical trial, Foster and colleagues randomly assigned treatment-naive patients to receive either 8 weeks (n = 23) or 12 weeks (n = 24) of Zepatier (elbasvir/grazoprevir [EBR/GZR], Merck) with Sovaldi (sofosbuvir, Gilead Sciences). Treatment-experienced patients received 12 weeks of EBR/GZR with sofosbuvir with (n = 18) or without ribavirin (n = 17), or 16 weeks of EBR/GZR with sofosbuvir without ribavirin (n = 18).

Sustained virologic response rates were 91% in treatment-naive patients treated for 8 weeks and 96% in those treated for 12 weeks.

SVR rates were 94% in treatment-experienced patients treated for 12 weeks with ribavirin, 100% in those treated for 12 weeks without ribavirin, and 94% in those treated for 16 weeks without ribavirin.

The SVR rate was 97% among 87 patients with NS3 resistance-associated substitutions (RASs) at baseline. The SVR rate was 98% among 50 patients with NS5A RASs at baseline, and 100% in the five patients with NS5B RASs at baseline.

Most adverse events were mild to moderate in severity. No treatment-naive patients experienced serious adverse events. Five treatment-experienced patients experienced severe adverse events, including pneumonia, chest pain, opiate overdose and two cases of cellulitis. One patient with cellulitis discontinued treatment.

“Efficacy was high in both treatment-naive and -experienced participants, and all participants with the Y93H RASs at baseline who received at least 12 weeks of [EBR/GZR with sofosbuvir] achieved SVR,” the researchers concluded. “This was a single-arm study with no comparator treatment arm, and therefore indirect comparisons with other treatments should be made with caution. Most participants also had well-compensated cirrhosis, so these data should not be extrapolated to participants with decompensated disease.” – by Talitha Bennett

Disclosure: Foster reports he received grants or research support from Chughai, Roche and Springbank; is a speaker for Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Merck, Roche and Tibotec; advises for Alnylam, Boehringer Ingelheim, Bristol-Myers Squibb, Chughai, Gilead, GlaxoSmithKline, Idenix, Janssen, Novartis and Tibotec; and is a board member of Boehringer Ingelheim. Please see the full study for the other authors’ relevant financial disclosures.

Zepatier demonstrated high efficacy among patients with hepatitis C genotype 3, regardless of treatment experience or baseline resistance-associated substitutions, according to recently published data.

“People with HCV [genotype 3] infection and cirrhosis who have failed previous treatment attempts are generally regarded as one of the most difficult-to-treat populations with HCV infection,” Graham R. Foster, MD, from the Queen Mary University, London, and colleagues wrote. “Additional treatment options are therefore required for this population, and increasing the barrier to resistance through the introduction of a third mechanistically distinct antiviral agent represents a rational solution to overcoming resistance-associated failure.”

In a phase 2 clinical trial, Foster and colleagues randomly assigned treatment-naive patients to receive either 8 weeks (n = 23) or 12 weeks (n = 24) of Zepatier (elbasvir/grazoprevir [EBR/GZR], Merck) with Sovaldi (sofosbuvir, Gilead Sciences). Treatment-experienced patients received 12 weeks of EBR/GZR with sofosbuvir with (n = 18) or without ribavirin (n = 17), or 16 weeks of EBR/GZR with sofosbuvir without ribavirin (n = 18).

Sustained virologic response rates were 91% in treatment-naive patients treated for 8 weeks and 96% in those treated for 12 weeks.

SVR rates were 94% in treatment-experienced patients treated for 12 weeks with ribavirin, 100% in those treated for 12 weeks without ribavirin, and 94% in those treated for 16 weeks without ribavirin.

The SVR rate was 97% among 87 patients with NS3 resistance-associated substitutions (RASs) at baseline. The SVR rate was 98% among 50 patients with NS5A RASs at baseline, and 100% in the five patients with NS5B RASs at baseline.

Most adverse events were mild to moderate in severity. No treatment-naive patients experienced serious adverse events. Five treatment-experienced patients experienced severe adverse events, including pneumonia, chest pain, opiate overdose and two cases of cellulitis. One patient with cellulitis discontinued treatment.

“Efficacy was high in both treatment-naive and -experienced participants, and all participants with the Y93H RASs at baseline who received at least 12 weeks of [EBR/GZR with sofosbuvir] achieved SVR,” the researchers concluded. “This was a single-arm study with no comparator treatment arm, and therefore indirect comparisons with other treatments should be made with caution. Most participants also had well-compensated cirrhosis, so these data should not be extrapolated to participants with decompensated disease.” – by Talitha Bennett

Disclosure: Foster reports he received grants or research support from Chughai, Roche and Springbank; is a speaker for Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Merck, Roche and Tibotec; advises for Alnylam, Boehringer Ingelheim, Bristol-Myers Squibb, Chughai, Gilead, GlaxoSmithKline, Idenix, Janssen, Novartis and Tibotec; and is a board member of Boehringer Ingelheim. Please see the full study for the other authors’ relevant financial disclosures.