Grazoprevir/Elbasvir Hepatitis C Treatment Works Wells for People Who Inject Drugs

alt

Merck's grazoprevir/elbasvir hepatitis C regimen was well-tolerated and cured more than 90% of injection drug users receiving opioid substitution therapy, according to results from the C-EDGE CO-STAR study published in the August 9 online edition of Annals of Internal Medicine. The investigators reported that adherence was good even though many study participants continued to use illicit drugs.

Hepatitis C virus (HCV) is easily transmitted through shared equipment for drug injection, and current and former injection drug users have high rates of infection. But many providers and insurers still consider people who inject drugs poor candidates for treatment, and active drug users have been excluded from many trials of the new direct-acting antiviral agents.

Gregory Dore from the Kirby Institute at the University of New South Wales and colleagues conducted the Phase 3 C-EDGE CO-STAR trial (NCT02105688) to evaluate the HCV NS3/4A protease inhibitor grazoprevir plus the NS5A inhibitor elbasvir for injection drug users receiving opioid substitution therapy. This combination previously demonstrated cure rates of 90% or better in other populations.

CO-STAR enrolled 301 previously untreated chronic hepatitis C patients in Australia, Canada, France, Germany, Israel, the Netherlands, New Zealand, Norway, Spain, Taiwan, the U.K., and the U.S.

Three-quarters were men, about 80% were white, and the median age was approximately 48 years. Most (76%) had hard-to-treat HCV subtype 1a, followed by 1b (15%), 4(6%), and 6 (3%, or 9 patients). About 20% had liver cirrhosis, 7% were coinfected with HIV, and over half had high HCV viral load at baseline (>2,000,000 IU/mL).

Entry criteria included stable opioid agonist therapy (80% methadone, 20% buprenorphine) for at least 3 months and keeping at least 80% of appointments.Nevertheless, nearly 60% tested positive for non-prescribed drug use on baseline urine screens -- including about 20% positive for opioids -- but they were not excluded from the study.

Participants were randomly assigned (2:1) to receive either immediate treatment with grazoprevir/elbasvir given as a once-daily fixed-dose coformulation (100 mg/50 mg) or placebo for 12 weeks. At that point the study was unblended, and after 4 weeks the placebo recipients were also given grazoprevir/elbasvir on an open-label basis.

The primary endpoint was sustained virological response, or undetectable HCV RNA at 12 weeks post-treatment (SVR12) -- usually considered a cure. In the primary analysis people who were apparently reinfected with HCV after initial response were considered treatment failures. Dore previously presented these findings in part at the 2015 AASLD Liver Meeting.

Results

"Patients with HCV infection who were receiving [opiate agonist therapy] and treated with elbasvir-grazoprevir had high rates of SVR12, regardless of ongoing drug use," the study authors concluded. "These results support the removal of drug use as a barrier to interferon-free HCV treatment for patients receiving [opiate agonist therapy]."

The researchers cautioned that these findings may not be generalizable to injection drug users who are not receiving opiate agonist therapy, and they do not apply to individuals with HCV genotype 3, which is common strain among people who inject drugs.

They noted in their discussion that high levels of HCV reinfection might compromise the benefits of treatment from both an individual patient and a public health perspective. In this study 3 of the 6 patients with probable reinfection subsequently cleared HCV RNA without additional treatment, "indicating that not all reinfection cases develop viral persistence and drawing attention to the possible role of an augmented HCV-specific immune response after DAA therapy," they wrote. An ongoing extension of this study will look at drug use behavior and the incidence and outcome of HCV reinfection over a 3-year period after treatment.

"C-EDGE CO-STAR is the first Phase 3 clinical trial dedicated to evaluating direct-acting antiviral therapy for chronic hepatitis C infection in patients on opioid agonist therapy without excluding patients actively using drugs with high abuse potential," co-investigator Alain Litwin from Albert Einstein College of Medicine said in a Merck press release. "This study demonstrates that people who inject drugs can be effectively treated with direct-acting antiviral therapy."

8/11/16

Reference

GJ Dore, F Altice, AH Litwin, et al. Elbasvir-Grazoprevir to Treat Hepatitis C Virus Infection in Persons Receiving Opioid Agonist Therapy: A Randomized Trial. Annals of Internal Medicine. August 8, 2016 (online ahead of print).

Other Source

Results from Merck’s Phase 3 Study Evaluating ZEPATIER (elbasvir and grazoprevir) in Patients with Chronic Hepatitis C Receiving Treatment for Opioid Dependence Published in Annals of Internal Medicine. Press release. August 8, 2016.