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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From NY Times: Are New Drugs for Hepatitis C Safe? A Report Raises Concerns
Drugs approved in recent years that can cure hepatitis C may have severe side effects, including liver failure, a new report suggests. The number of adverse events appears relatively small, and the findings are not conclusive. But experts said the report was a warning that should not be ignored…
The report will be published online on Wednesday [1/25/17] by the Institute for Safe Medication Practices, a nonprofit in Horsham, Pa., that studies drug safety. Its findings are based on the group’s analysis of the Food and Drug Administration’s database of reports from doctors around the world of adverse events that might be related to medications.
In October, the F.D.A. identified the first major safety problem caused by the nine antiviral drugs. In 24 patients, the drugs wiped out hepatitis C — but also reactivated hepatitis B infections that had been dormant. Two of those patients died, and one needed a liver transplant. The agency said there were probably additional cases that had not been reported.
As a result, the agency required that a boxed warning, its most prominent advisory, be added to the labeling of the newer antivirals, telling doctors to screen and monitor for hepatitis B in all patients taking the drugs for hepatitis C. Infection with both viruses is not common, and how the reactivation occurs is not known. The problem was not detected during premarket testing of the drugs because patients who currently had hepatitis B or who had a history of it were not allowed into the studies…
The other cases of liver failure are a separate problem. He said it was important for doctors prescribing the newer drugs to test patients’ liver function thoroughly first, because liver disease can be deceptive
My take: Overall, these newer Hepatitis C medications represent a tremendous achievement. However, as with most medications, rare serious problems can occur and in some cases may be preventable.
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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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A new study shows an HCV sustained virological remission of 99% in a study of genotypes 1, 2, 4, 5, and 6.
December 31, 2015 | J.J. Feld and Others
Published Online: November 16, 2015
Here’s a terrific 2 minute summary from NEJM.