In the Journals

Mavyret safe, effective for HCV genotype 3 regardless of cirrhosis

Patients with hepatitis C genotype 3, with or without compensated cirrhosis, achieved significantly high rates of sustained virologic response after treatment with Mavyret and experienced no significant adverse events related to the drug, according to recently published data from a phase 3 study.

Fred Poordad, MD
Fred Poordad

“The field has come a long way in a short time with multiple outstanding regimens now approved for HCV treatment,” Fred Poordad, MD, from the Texas Liver Institute and University of Texas Health Science Center, San Antonio, and study investigator told Healio.com/Hepatology. “One of the remaining challenges is the genotype 3 patient, particularly those with cirrhosis and past treatment failure. The combination of glecaprevir/pibrentasvir gives clinicians an excellent option, with high SVR rates using 8 weeks in the treatment naive non-cirrhotics, all the way up to 16 weeks in the treatment failure patient. We should now be able to eradicate virus in almost every HCV patient out there, which is great news.”

The researchers enrolled 131 patients with HCV genotype 3 from the United States, Australia, Canada, France, New Zealand and the United Kingdom in part 3 of the SURVEYOR-II study. Most patients were men (67%) and Caucasian (89%).

Treatment arms included 44 treatment-experienced patients without cirrhosis who received 12 or 16 weeks of treatment with Mavyret (glecaprevir/pibrentasvir, AbbVie); 40 treatment-naive patients with compensated cirrhosis who received 12 weeks of treatment; and 47 treatment-experienced patients with compensated cirrhosis who received 16 weeks of treatment.

Sustained virologic response

The SVR rate for treatment-naive patients with cirrhosis was 98% (95% CI, 87-99), including one patient who was lost to follow-up but did achieve SVR at 4 weeks. Treatment-experienced patients with cirrhosis achieved an SVR rate of 96% (95% CI, 86-99) after 16 weeks.

Treatment-experienced patients without cirrhosis in the 12-week arm achieved an SVR rate of 91% (95% CI, 72-97) and those in the 16-week arm had a rate of 95% (95% CI, 78-99). The difference in SVR rates was –4.5% (95% CI, –23.6 to –13.9). Two patients in the 12-week arm and one patient in the 16-week arm relapsed. Specifically, patients with prior sofosbuvir-based treatment experience achieved an SVR rate of 98% (95% CI, 88-99).

Compared with patients without baseline NS3 polymorphisms (96%; 95% CI, 91-99), patients with NS3 polymorphisms achieved an SVR rate of 95% (95% CI, 75-99).

Among patients with cirrhosis, the SVR rates for those without NS5A polymorphisms was 97% (95% CI, 90-99) compared with a 100% rate in those with NS5A polymorphisms (95% CI, 80-100). Treatment-experienced patients without cirrhosis and without NS5A polymorphisms also achieved an SVR rate of 100% (95% CI, 90-100). Among treatment experienced patients with NS5A polymorphism, four of six patients achieved SVR at 12 weeks and two of three achieved SVR at 16 weeks,.

Tolerance

The researchers classified most of the adverse events observed as mild and no patients discontinued treatment due to adverse events. The most common events included fatigue (22%) and headache (19%). Additionally, no patients experienced clinically significant elevated alanine aminotransferase levels.

According to the researchers, the six serious adverse events reported were not caused by the treatment drug. None of the patients with serious adverse events discontinued treatment and no patients experienced of drug-induced liver injury or hepatic decompensation.

“Treatment with [glecaprevir/pibrentasvir] was safe and well-tolerated, regardless of treatment duration or baseline patient characteristics,” the researchers concluded. “Previous-generation NS3/4A protease inhibitor-containing regimens have been associated with AEs, including severe rash, marked hyperbilirubinemia, neutropenia, anemia, and elevated ALT, particularly in patients with cirrhosis. However, all of these events were absent or rarely observed in SURVEYOR-II Part 3, even in patients with compensated cirrhosis.” – by Talitha Bennett

Disclosure: Wyles reports he received grants or research support from AbbVie, Gilead, Merck and Tacere Therapeutics, and is a consultant or advisor for AbbVie, Gilead and Merck. Please see the full study for the other researchers’ relevant financial disclosures.

Patients with hepatitis C genotype 3, with or without compensated cirrhosis, achieved significantly high rates of sustained virologic response after treatment with Mavyret and experienced no significant adverse events related to the drug, according to recently published data from a phase 3 study.

Fred Poordad, MD
Fred Poordad

“The field has come a long way in a short time with multiple outstanding regimens now approved for HCV treatment,” Fred Poordad, MD, from the Texas Liver Institute and University of Texas Health Science Center, San Antonio, and study investigator told Healio.com/Hepatology. “One of the remaining challenges is the genotype 3 patient, particularly those with cirrhosis and past treatment failure. The combination of glecaprevir/pibrentasvir gives clinicians an excellent option, with high SVR rates using 8 weeks in the treatment naive non-cirrhotics, all the way up to 16 weeks in the treatment failure patient. We should now be able to eradicate virus in almost every HCV patient out there, which is great news.”

The researchers enrolled 131 patients with HCV genotype 3 from the United States, Australia, Canada, France, New Zealand and the United Kingdom in part 3 of the SURVEYOR-II study. Most patients were men (67%) and Caucasian (89%).

Treatment arms included 44 treatment-experienced patients without cirrhosis who received 12 or 16 weeks of treatment with Mavyret (glecaprevir/pibrentasvir, AbbVie); 40 treatment-naive patients with compensated cirrhosis who received 12 weeks of treatment; and 47 treatment-experienced patients with compensated cirrhosis who received 16 weeks of treatment.

Sustained virologic response

The SVR rate for treatment-naive patients with cirrhosis was 98% (95% CI, 87-99), including one patient who was lost to follow-up but did achieve SVR at 4 weeks. Treatment-experienced patients with cirrhosis achieved an SVR rate of 96% (95% CI, 86-99) after 16 weeks.

Treatment-experienced patients without cirrhosis in the 12-week arm achieved an SVR rate of 91% (95% CI, 72-97) and those in the 16-week arm had a rate of 95% (95% CI, 78-99). The difference in SVR rates was –4.5% (95% CI, –23.6 to –13.9). Two patients in the 12-week arm and one patient in the 16-week arm relapsed. Specifically, patients with prior sofosbuvir-based treatment experience achieved an SVR rate of 98% (95% CI, 88-99).

Compared with patients without baseline NS3 polymorphisms (96%; 95% CI, 91-99), patients with NS3 polymorphisms achieved an SVR rate of 95% (95% CI, 75-99).

Among patients with cirrhosis, the SVR rates for those without NS5A polymorphisms was 97% (95% CI, 90-99) compared with a 100% rate in those with NS5A polymorphisms (95% CI, 80-100). Treatment-experienced patients without cirrhosis and without NS5A polymorphisms also achieved an SVR rate of 100% (95% CI, 90-100). Among treatment experienced patients with NS5A polymorphism, four of six patients achieved SVR at 12 weeks and two of three achieved SVR at 16 weeks,.

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Tolerance

The researchers classified most of the adverse events observed as mild and no patients discontinued treatment due to adverse events. The most common events included fatigue (22%) and headache (19%). Additionally, no patients experienced clinically significant elevated alanine aminotransferase levels.

According to the researchers, the six serious adverse events reported were not caused by the treatment drug. None of the patients with serious adverse events discontinued treatment and no patients experienced of drug-induced liver injury or hepatic decompensation.

“Treatment with [glecaprevir/pibrentasvir] was safe and well-tolerated, regardless of treatment duration or baseline patient characteristics,” the researchers concluded. “Previous-generation NS3/4A protease inhibitor-containing regimens have been associated with AEs, including severe rash, marked hyperbilirubinemia, neutropenia, anemia, and elevated ALT, particularly in patients with cirrhosis. However, all of these events were absent or rarely observed in SURVEYOR-II Part 3, even in patients with compensated cirrhosis.” – by Talitha Bennett

Disclosure: Wyles reports he received grants or research support from AbbVie, Gilead, Merck and Tacere Therapeutics, and is a consultant or advisor for AbbVie, Gilead and Merck. Please see the full study for the other researchers’ relevant financial disclosures.