Mark Fuerst

A single-tablet regimen of sofosbuvir, velpatasvir, and voxilaprevir for 12 weeks is safe, well tolerated, and highly effective in patients with chronic hepatitis C virus (HCV) infection who had previously failed treatment with an NS5A inhibitor, according to a new study.

The combination led to a 97 percent rate of sustained virologic response 12 weeks after the end of treatment (SVR12) in an open-label substudy of the POLARIS-1 trial.

Previously, the phase 3 POLARIS-1 trial showed the effectiveness of the direct-acting antiviral (DAA) combination of sofosbuvir (an NS5B inhibitor), velpatasvir (an NS5A inhibitor), and voxilaprevir (an NS3/4A protease inhibitor) and served as the basis for U.S. and European approvals. 

The researchers published the 

 on May 30, 2018, in The Lancet Gastroenterology & Hepatology.

These latest results “add to the confidence of the regimen by considerably increasing the number of patients treated with it. A salvage regimen for this population represents an important advance for patients with limited retreatment options,” said the researchers led by Marc BourliÃ¨re, MD of the Hospital Saint Joseph, Marseilles, France.

He noted that POLARIS-1 is the only phase 3 registration study dedicated to enrollment of patients who were previously treated with NS5A inhibitors, and there have been few data for retreatment of these patients.

The substudy included 147 patients who had initially received placebo in POLARIS-1. They received a combination tablet of sofosbuvir (400 mg), velpatasvir (100 mg), and voxilaprevir (100 mg) once daily for 12 weeks.

More than three-quarters (113 patients) had HCV genotype 1a, while 30 patients had genotype 1b and 2 patients had genotype 6. One-third of patients had compensated cirrhosis. About two-thirds (91 patients) had previously received the NS5A inhibitor ledipasvir, while 27 patients had received daclatasvir and 24 received ombitasvir.

Most patients (89 percent) had baseline NS5A or NS3 resistance-associated substitutions, which had no discernible impact on SVR rates. The combination regimen produced high SVR rates regardless of cirrhosis status or previous treatment regimen.

All 147 patients completed treatment, and 143 patients (97 percent) achieved SVR12. Four (3 percent) patients had virological relapse; all had HCV genotype 1a infection and one patient also had compensated cirrhosis.

The most common adverse events were fatigue (21 percent), headache (20 percent), diarrhea (19 percent), and nausea (14 percent). No deaths, treatment discontinuations, or treatment-related serious adverse events occurred.

In an accompanying editorial, Imam Waked, MD, from the National Liver Institute in Menoufiya, Egypt, wrote: “Since sofosbuvir-velpatasvir-voxilaprevir results in a very high SVR rate in patients who have not responded to all types of direct-acting antiviral therapy, regardless of genotype and of the presence of NS3 or NS5A resistance-associated substitutions, its use as a first-line treatment in untreated patients is appealing.”

He noted that the use of this combination as first-line therapy for 12 weeks still needs to be further evaluated.

This regimen is a treatment of choice for HCV patients when NS5A or NS3 DAA therapy fails. The combination is recommended in clinical practice guidelines from the American Association for the Study of Liver Diseases and Infectious Diseases Society of America, and from the European Association for the Study of the Liver.

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Sofosbuvir-velpatasvir-voxilaprevir provides salvage therapy for NS5A failures

Direct-acting antiviral combination retreats chronic hepatitis C failures 

Despite the availability of new, highly successful direct-acting antiviral (DAA) regimens, more than one third of chronic hepatitis C (HCV) patients are denied access to treatment by their insurance provider, according to a new study.

Some 35.5 percent of patients who were prescribed a DAA regimen for chronic HCV were denied the treatment by their insurer. Denials of treatment were more common among patients with commercial insurance (52.4 percent) compared with those with Medicaid (34.5 percent) or Medicare (14.7 percent).

What’s more, the proportion of HCV patients whose DAA prescriptions were denied by their insurance company increased over a period of 16 months. The incidence of absolute denial increased across the study period from 27.7 percent in the first quarter to 43.8 percent in the last quarter.

“Absolute denials of DAA regimens by insurers have remained high and increased over time, regardless of type of insurance. These data provide evidence of a continued lack of access to HCV therapy across insurance types. To achieve the goal of HCV elimination, access to antiviral treatment must be improved,” stated the authors, led by senior author Vincent Lo Re, III, MD, MSCE, associate professor of medicine at the University of Pennsylvania.

The researchers published their results on June 1, 2018 in Open Forum Infectious Diseases.

Lo Re and colleagues conducted a prospective cohort study among patients who had a DAA prescription submitted from January 2016 to April 2017 to Diplomat Pharmacy, Inc., which provides HCV pharmacy services across the country. The main outcome was absolute denial of DAA prescription, defined as lack of fill approval by the insurer. They calculated the incidence of absolute denial, overall and by insurance type, for the 16-month study period and each quarter.

The system received prescriptions for DAAs from 9,025 patients, median 57 years old, including 4,702 covered by Medicaid, 2,502 covered by commercial insurance, and 1,812 covered by Medicare. More than half of the patients were prescribed a combination of sofosbuvir-ledipasvir, with or without ribavirin.

A total of 45 states were examined where a DAA prescription was submitted. Eight states contributed the vast majority (90 percent) of prescriptions. Pennsylvania had the highest proportion (31.5 percent), followed by California (23.6 percent) and Michigan (14.3 percent). In terms of overall incidence of absolute DAA denial in these eight states, Maryland had the highest incidence (51.5 percent), followed by Delaware (49.1 percent), New Jersey (47.2 percent), and Pennsylvania (45.7 percent).

The reasons for this increase in coverage denials remain unclear. “Insurers may be electing to prioritize certain patient populations, such as those who have advanced hepatic fibrosis/cirrhosis or who abstain from alcohol and injection drug use, when deciding whether to allocate DAA treatments,” they state.

The study has important clinical implications. “Persons denied access to HCV therapy remain at risk for the development of hepatic fibrosis, cirrhosis, liver decompensation, and hepatocellular carcinoma. Denial of DAA treatment can also lead to ongoing HCV-associated inflammation, which might increase the risk of extrahepatic complications,” state the authors.

They also recommended that “public and private insurers should remove restrictions to DAAs that are not medically indicated and offer treatment to all chronic HCV-infected patients.”

Despite the availability of new, highly successful direct-acting antiviral (DAA) regimens, more than one third of chronic hepatitis C (HCV) patients are denied access to treatment by their insurance provider, according to a new study.

Author | Mark Fuerst

Articles

Direct-acting antiviral combination retreats chronic hepatitis C failures

More than one-third of hepatitis C patients denied insurance coverage