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EASL Paris: AbbVie 3D Regimen for 8 Weeks Cures Almost All HCV Genotype 1b Patients

AbbVie's paritaprevir-based 3D regimen taken for just 8 weeks without ribavirin led to sustained virological response in 98% of easier-to-treat non-cirrhotic patients with hepatitis C virus (HCV) genotype 1b, according to findings from the GARNET study, presented last week at the EASL special conference New Perspectives in Hepatitis C Virus Infection - The Roadmap for Cure in Paris.

Direct-acting antiviral therapy has revolutionized treatment for hepatitis C, but researchers continue to look for shorter-duration regimens that would be more convenient and less costly.

The 3D regimen (marketed as Viekira Pak or Viekirax XR in the U.S. and Viekirax/Exviera in Europe) consists of the HCV protease inhibitor paritaprevir boosted with ritonavir, the NS5A inhibitor ombitasvir, and the NS5B polymerase inhibitor dasabuvir. The approved indication in the U.S. and E.U. is 12 weeks of the 3D combo alone for people with HCV genotype 1b with or without liver cirrhosis, 12 weeks of 3D plus ribavirin for people with harder-to-treat genotype 1a without cirrhosis, and 24 weeks of 3D plus ribavirin for genotype 1a patients with compensated cirrhosis.

HCV genotype 1b is the most common type in Europe and Asia, and the second most common in the U.S. As previously reported in 2014, the Phase 3 PEARL-III trial showed that the 3D regimen taken alone for 12 weeks cured 99% of previously untreated genotype 1b patients without cirrhosis, while 3D plus ribavirin cured 99.5%.

Based on these excellent results, Tania Welzel from J.W. Goethe University in Frankfurt and colleagues conducted the GARNET study to evaluate whether a shorter 8-week regimen of 3D without ribavirin would work as well for this easy-to-treat population.

The Phase 3 GARNET trial enrolled 166 chronic hepatitis C patients with no prior treatment experience at 20 sites. More than half (57%) were women, almost all were white, and the median age was 53 years. Almost all (98%) had HCV genotype 1b, as per the entry criteria, but 3 people with other genotypes were included (1a, 1d, and 6). The media baseline HCV viral load was 6 log IU/mL; 93% had <6,000,000 IU/mL and 42% had <800,000 IU/mL. Most had absent to moderate liver fibrosis (stage F0-F2), but 9% had advanced fibrosis (stage F3); none had cirrhosis, as specified in the entry criteria. People with HIV or hepatitis B coinfection were excluded.

All participants in this open-label, single-arm study received the paritaprevir/ritonavir/ombitasvir coformulation (150/100/25 mg) once-daily plus dasabuvir (250 mg) twice-daily for 8 weeks.

The primary endpoint was sustained virological response, or continued undetectable HCV RNA (<15 IU/mL) at 12 weeks after completing treatment (SVR12).

Results

• The SVR12 rate was 98% in an intent-to-treat analysis that included all participants who received at least 1 dose of treatment.
• The SVR12 rate rose to 99% in a modified analysis that excluded individuals with HCV genotypes other than 1b and a participant who discontinued treatment early.

o   3 participants experienced virological failure:

o   2 genotype 1b patients with F3 fibrosis relapsed after treatment;

• The sole genotype 6 patient did not achieve viral suppression.
• Cure rates were similar for men and women, people over age 65, and obese patients.
• People with baseline HCV RNA >800,000 IU/mLdid equally well, but the SVR12 rate fell to 92% for those with >6,000,000.
• The SVR rate was 99% for people with F0-F2 fibrosis, but dropped to 87% for those with stage F3.
• All 66 patients with either only NS5A or only NS5B resistance-associated viral polymorphisms at baseline were cured, as were 17 of 18 (94%) who had both NS5A and NS5B resistance.
• Treatment was generally safe and well-tolerated.
• 1 person discontinued treatment due to elevated bilirubin, but still went on to achieve SVR12.
• There were 2 serious adverse events (fainting and gastroenteritis), both deemed unrelated to the study drugs.
• The most common adverse events were headache (21%), fatigue (17%), nasopharyngitis (8%), pruritus (8%), nausea (6%), and muscle weakness (5%).

"The 98% SVR rate demonstrated that treatment-naive genotype 1b patients without cirrhosis can be effectively treated with 3D for 8 weeks," the researchers concluded. "Both genotype 1B patients who experienced virologic failure had F3 fibrosis at baseline."

Based on these findings, the newly released EASL hepatitis C treatment recommendations now say that previously untreated genotype 1b patients without cirrhosis can be treated with the 3D regimen for either 8 or 12 weeks.

9/28/16

Reference

TM Welzel, S Zeuzem, EO Dumas, et al. GARNET: High SVR rates following eight-week treatment with ombitasvir/paritaprevir/ritonavir + dasabuvir for patients with HCV genotype 1b infection. New Perspectives in Hepatitis C Virus Infection - The Roadmap for Cure. Paris, September 23-24, 2016. Abstract 163.

Other Source

AbbVie. AbbVie Presents Data on Eight-Week Treatment of VIEKIRAX (ombitasvir/paritaprevir/ritonavir tablets) + EXVIERA (dasabuvir tablets) in Patients with Genotype 1b Chronic Hepatitis C. Press release. September 23, 2016.