While the emergence of multiple highly-active agents for Hepatitis C has been a terrific advance, there are a small subset of patients who have not responded to them in almost all clinical trials. A recent study (M Bourliere et al. NEJM 2017; 376: 2134-46) has identified a highly-effective combination regimen for this population: sofosbuvir/velpatasvir/voxilaprevir x 12 weeks
The authors conducted two phase 3 trials in patients who had not responded to a direct-acting antiviral (DAA) regimen previously. POLARIS-1 and POLARIS-4. 46% of patients had compensated cirrhosis Key findings:
- POLARIS-1: 96% of combination group had a sustained virologic response (SVR) compared with 0% of patients receiving placebo
- POLARIS-4: the triple combination had a SVR of 98%, whereas 90% had SVR with dual therapy (sofosbuvir-velpatasvir)
- Among patients receiving active treatment, less than 1% discontinue treatment due to advers events.
My take: This triple therapy is highly effective in patients who were previously-treated with DAA for HCV.
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While access to HCV treatment remains the biggest obstacle, recent studies show that the rates of HCV eradication, even in the toughest cases, now approaches 100%.
- E Lawitz et al. Gastroenterol 2016; 151: 893-901.
- EJ Gane et al. Gastroenterol 2016; 151: 902-9.
- Editorial: M Buti pgs 795-8.
Most prior studies examined the use of two direct-acting antivirals (DAAs) with or without ribavirin. These DAAs targeted nonstructural (NS) proteins necessary for HCV replication: NS3 protease, NS5B polymerase, and NS5A protein.
These two new studies examined whether treatment with a DAA targeting all 3 NS proteins would be effective and possibly allow shorter treatments. It is noted that currently only treatment-naive genotype 1 (w/o cirrhosis) patients have a regimen that is recommended for only 8 weeks; these patients also should have HCV-RNA<6,000,000 IU/mL.
Lawitz et al studied the combination of sofosbuvir-velpatasvir and GS-9857 (voxilaprevir) for 6-8 weeks (one treatment group received ribavirin); n=197. Among treatment-naive patients w/o cirrhosis, SVR12 was 100% after 8 weeks of treatment and 94% of treatment-naive patients with cirrhosis. Among treatment-experienced patients treated for 12 weeks, 100% of all patients (w and w/o cirrhosis) achieved SVR12.
Gane et al studied the effectiveness of the combination of sofosbuvir-velpatasvir and GS-9857 in HCV genotypes 2, 3, 4, and 6 (as well as 1 with 1b); n=128. After 8 weeks of treatment, SVR12s were achieved in 93% of treatment-naive patients with cirrhosis. After 12 weeks, treatment-experienced patients with and without cirrhosis had SVR12s of 97% and 100% respectively.
My take: This combination of therapies should allow shorter treatment regimens in treatment-naive patients and effective rescue therapy for previous DAA failures. Now that we can cure almost everyone with HCV, how do make therapies affordable and accessible?
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