AASLD 2015: Grazoprevir/ Elbasvir Shows High Cure Rate for People Who Inject Drugs

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Merck's grazoprevir/elbasvir coformulation demonstrated an overall sustained response rate of 92% for injection drug users receiving opioid substitution therapy in the C-EDGE CO-STAR study, according to a presentation at the 2015 AASLD Liver Meeting taking place this week in San Francisco. Participants maintained good adherence and had a high cure rate even though many continued to use illicit drugs.

Hepatitis C virus (HCV) is easily transmitted through sharing drug injection equipment, and current and former injection drug users have high rates of infection (50% to 80% in some studies). But many providers and insurers still consider people who inject drugs (PWID) to be poor candidates for treatment, and active drug users have been excluded from most trials of new direct-acting antiviral agents.

Gregory Dore from the Kirby Institute at the University of New South Wales presented findings from the Phase 3 C-EDGE CO-STAR trial, which evaluated Merck's HCV NS3/4A protease inhibitor grazoprevir and HCV NS5A inhibitor elbasvir in PWID receiving opioid agonist therapy using methadone or buprenorphine. This combination has previously demonstrated cure rates of 90% or better in non-PWID populations.

CO-STAR enrolled 301 previously untreated people with HCV genotypes 1, 4, or 6 (including 76% with hard-to-treat HCV subtype 1a). About three-quarters were men, about 80% were white, and the median age was 48 years. About 1 in 5 had liver cirrhosis and 7% were coinfected with HIV. Just over half had high HCV viral load at baseline (>2,000,000 IU/mL).

Participants were required to be on stable opioid agonist therapy (mostly methadone) for at least 3 months and to have consistently kept at least 80% of their appointments.Urine screens were done to test for non-prescribed drug use -- with nearly 60% testing positive at study entry -- but people were not excluded or removed from the study on this basis.

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

The researchers looked at both a full analysis population that included all participants, and a modified population that excluded people who discontinued the study for non-treatment-related reasons (such as loss to follow-up) or who became reinfected with a different viral type after HCV clearance. The primary study endpoint was sustained virological response, or continued undetectable viral load at 12 weeks post-treatment (SVR12), in the modified population.

Results

Based on these findings, the researchers concluded that grazoprevir/elbasvir "demonstrated high efficacy in genotype 1 and 4-infected patients receiving opiate agonist therapy."

The sustained response rates and adherence levels seen in C-EDGE CO-STAR compare favorably to those of people who were not injecting drug users in the C-EDGE Treatment-naiveand C-EDGE Treatment-experiencedstudies.

"The safety and high efficacy convincingly demonstrate the benefits of treating HCV within this population," Dore said. "Such evidence should enhance access to new HCV therapies, including removal of restrictions to access in many settings based on illicit drug use. This study offers reassurance to providers who are concerned that patients who actively use illicit drugs will not be adherent to their chronic HCV treatment."

Dore noted that the CO-STAR study has been extended to follow participants for 2 years to evaluate longer-term outcomes. He said Kirby Institute researchers are looking at drug injection networks to further understand and try to prevent HCV reinfection.

11/15/15

References

G Dore, F Altice, AH Litwin, et al. C-EDGE CO-STAR: Efficacy of Grazoprevir and Elbasvir in Persons who Inject Drugs (PWID) Receiving Opioid Agonist Therapy. AASLD Liver Meeting 2015. San Francisco, November 13-17, 2015. Abstract 40.

Merck. Merck Announces Presentation of Phase 3 Results of Investigational Elbasvir/Grazoprevir in People with Chronic Hepatitis C Genotypes 1, 4 or 6 Infection Who Inject Drugs and Are on Opioid Agonist Therapy. Press release. November 14, 2015.

AASLD. Eliminating Barriers to Treatment for Patients With HCV Who Inject Drugs. Press release. November 15, 2015.