ILC 2017 Glecaprevir/pibrentasvir 95% SVR12 in HCV Geno 3 treatment naïve, non-cirrhotic patients

ILC 2017: Study demonstrates the efficacy of an investigational, pan-genotypic treatment in patients with a difficult to cure subgroup of Hepatitis C

Co-formulation of glecaprevir/pibrentasvir achieved a 95% SVR12 rate in treatment naïve, non-cirrhotic patients with chronic Hepatitis C virus genotype 3 

April 21, 2017, Amsterdam, The Netherlands: Study results presented today demonstrate that the oral, once-daily treatment regimen of glecaprevir/pibrentasvir (G/P) resulted in 95% sustained virologic response rates at 12 weeks post treatment (SVR12) in patients with Hepatitis C virus (HCV) genotype 3. In the ENDURANCE-3 study, presented at The International Liver Congress™ 2017 in Amsterdam, The Netherlands, patients infected with HCV genotype 3 without cirrhosis and who had no previous treatment history were treated with the new regimen for eight or 12 weeks, which was well tolerated. G/P had a similar safety profile to the commonly used combination of sofosbuvir and daclatasvir for 12 weeks, to which G/P was actively compared in the study.

Around 180 million people globally have chronic HCV infection,1 including approximately 15 million people in the EU.2 Genotype 3 patients have become the most difficult subgroup of patients to cure.3 Although there have been recent advances in direct-acting antiviral therapies for HCV genotype 1, genotype 3 remains a challenge and is a highly prevalent strain of the virus globally.3

"While there has been great progress made in the treatment of patients with Hepatitis C, there remain limited options for those with genotype 3 disease. As such, we are pleased to see that the investigational combination of glecaprevir/pibrentasvir achieved high SVR12 rates, in treatment naïve, non-cirrhotic patients,” said Dr Graham Foster, Queen Mary University of London, United Kingdom and lead study author. “Treatment with this once-daily regimen for eight weeks could provide a highly efficacious and well-tolerated option for treatment naïve, non-cirrhotic patients with Hepatitis C, genotype 3, if approved by the regulatory authorities.”

ENDURANCE-3 is a Phase 3, open-label, active-controlled study in which 348 treatment naïve, non-cirrhotic HCV genotype 3 patients were randomised to receive 12 weeks of oncedaily therapy with either co-formulated glecaprevir/pibrentasvir, or with sofosbuvir plus daclatasvir. Subsequently, 157 patients were enrolled to receive glecaprevir/pibrentasvir for eight weeks. The primary endpoint of the study was the percentage of patients who achieved SVR12. 

SVR12 was achieved in 222/233 (95%) (95% confidence interval 93-98) of patients treated with glecaprevir/pibrentasvir for 12 weeks, and in 111/115 (97%) (95% confidence interval 91-99) of patients treated with sofosbuvir plus daclatasvir for 12 weeks. In patients treated with glecaprevir/pibrentasvir for eight weeks, SVR12 was achieved in 149/157 (95%) (95%

confidence interval 92-98) of patients. Relapse occurred in 1% of patients in both 12 week treatment regimens, and in 3% of patients in the eight week regimen. Adverse events (71%) were mostly mild and there were no serious treatment-related adverse events. 

“These results are more than encouraging, considering that treatment options for HCV genotype 3 are still suboptimal,” said Prof Francesco Negro, Divisions of Gastroenterology and Hepatology of Clinical Pathology, University Hospital of Geneva, Switzerland, and EASL Governing Board Member.

Press Release
Eight Weeks of Treatment with AbbVie’s Investigational, Pan-Genotypic, Ribavirin-Free HCV Regimen of Glecaprevir/Pibrentasvir (G/P) Achieved High SVR Rates in Challenging-to-Treat Genotype 3 Chronic HCV Patients
AbbVie announced high SVR rates were achieved with 8 weeks of treatment with its investigational, once daily, ribavirin-free, pan-genotypic regimen of glecaprevir/pibrentasvir (G/P) in patients with challenging-to-treat genotype 3 (GT3) chronic hepatitis C virus (HCV) infection. In results from AbbVie’s Phase 3 ENDURANCE-3 study, 95 percent (n=149/157) of GT3 chronic HCV-infected patients without cirrhosis and who were new to treatment achieved sustained virologic response at 12 weeks post-treatment (SVR₁₂) following 8 weeks of treatment with G/P.¹ These results will be featured as an oral presentation today at The International Liver Congress™ (ILC) 2017 in Amsterdam, The Netherlands.

In addition to evaluating 8 weeks of treatment with G/P, the ENDURANCE-3 study was designed to evaluate whether 12 weeks of G/P treatment is non-inferior to 12 weeks of sofosbuvir plus daclatasvir (SOF+DCV), a current standard of care for GT3 chronic HCV-infected patients.¹ SVR₁₂ rates of 95 percent were seen in both 8 weeks (n=149/157) and 12 weeks (n=222/233) of treatment with G/P.¹ Additionally, 12 weeks of treatment with G/P was demonstrated to be non-inferior to 12 weeks of treatment with SOF+DCV (97 percent, n=111/115).¹

GT3 is the second most common genotype globally, accounting for 18 percent of patients worldwide and 26 percent of patients in Europe.² Patients with GT3 HCV have more rapid disease progression, with the highest rates of associated fibrosis, steatosis (fatty liver), and hepatocellular carcinoma (HCC).³ Treatment guidelines with current standards of care recommend 12 weeks of treatment in GT3 patients without cirrhosis and who are new to treatment.⁴

Full results from ENDURANCE-3 are the latest to be released from AbbVie’s registrational studies in its G/P clinical development program, designed to investigate a faster path to virologic cure* for all major HCV genotypes (GT1-6) and with the goal of addressing areas of continued unmet need.

In the ENDURANCE-3 study, no patients who received 8 weeks of G/P discontinued treatment due to adverse events (AEs).¹ AEs were mostly mild (71 percent) in patients receiving both 8 and 12 weeks of G/P. The most common AEs (≥10 percent) in patients receiving 8 weeks and 12 weeks of G/P were headache (20 and 26 percent), fatigue (13 and 19 percent) and nausea (12 and 14 percent), respectively and with patients receiving 12 weeks of SOF+DCV treatment (headache 20 percent, fatigue 14 percent and nausea 13 percent).¹

Authorization applications for G/P are currently under review by regulatory authorities around the world. G/P has been granted accelerated assessment by the European Medicines Agency, and priority review designations by the U.S. Food and Drug Administration and Japanese Ministry of Health, Labour and Welfare. G/P is an investigational regimen and its safety and efficacy have not been established.

The ENDURANCE-3 study will be featured in the official ILC press conference on Friday, April 21 from 11:30 a.m. - 12:30 p.m. local time.

About the ENDURANCE-3 Study
ENDURANCE-3 is a Phase 3, open-label, active-controlled study evaluating patients who are new to treatment with HCV GT3 infection without cirrhosis. The study included 505 patients who were randomized to receive either 12 weeks of G/P (Arm A, n= 233) or 12 weeks of SOF+DCV (Arm B, n=115), with subsequently enrolled patients receiving 8 weeks of G/P (Arm C, n=157). The primary endpoint was the percentage of patients achieving SVR12. The rate of virologic failure was 1.7 percent (n=4/233) in Arm A, 0.8 percent (n=1/115) in Arm B and 3.8 percent (n=6/157) in Arm C.

Additional information on the clinical trials for G/P is available at www.clinicaltrials.gov.

About G/P
G/P is an investigational, pan-genotypic regimen that is being evaluated by AbbVie as a potential cure in 8 weeks for HCV patients without cirrhosis and who are new to treatment with direct-acting antivirals (DAAs)**, who make up the majority of HCV patients. AbbVie is also studying G/P in patients with specific treatment challenges, such as patients with genotype 3 HCV, patients who were not cured with previous DAA treatment and those with chronic kidney disease, including patients on dialysis.

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AbbVie's Investigational Regimen of Glecaprevir/Pibrentasvir (G/P) Achieved 99 Percent SVR(12) Rate in Chronic Hepatitis C Patients with Compensated Cirrhosis