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August 6, 2014
Pill-Only Antiviral Regimens Cure Many HCV Patients

San Antonio, TX—Even patients with the most difficult-to-treat forms of hepatitis C are benefiting from two new pill-only antiviral drug regimens, according to new studies which report that the therapies offer shorter, more effective treatment options with fewer side effects.

The studies, both published in the journal Lancet, focused on hepatitis C genotype 1, which is the most common genotype in the United States, Europe, North Asia, Australia, and South America, and one of the most difficult to treat.

Background in the articles point out that until recently, the standard of care for chronic HCV genotype 1 involved a combination of three drugs: ribavirin (RBV), pegylated interferon (PEG), and a protease inhibitor. The agents together inhibit viral replication and enhance the body’s immune response to eradicate the virus but at substantial burden on patients. The complex regimens, involving both injections and pills, sometimes require up to 18 tablets a day, last for a year, and cause serious side effects such as anemia and depression, according to the reports.

Direct-acting antiviral agents (DAAs), however, provide new opportunities for treatment while reducing the need for interferon and ribavirin and their potential side effects, according to the studies.

In the COSMOS study, a team of U.S. and European researchers led by Eric Lawitz, MD, from the Texas Liver Institute at the University of Texas Health Science Center in San Antonio, randomly assigned 167 patients with HCV genotypes 1a and 1b to a 12-week or 24-week course of once-daily sofosbuvir plus simeprevir with or without ribavirin.

Results indicate that, after just 12 weeks of treatment without ribavirin, 93% of participants—including those with cirrhosis and previous nonresponders to interferon-based treatment—had no detectable virus in their blood 3 months after treatment had stopped. They, in effect, were cured.

The 12-week sofosbuvir-plus-simeprevir regimen was well tolerated, with less than 2% of participants reporting serious adverse events or having to discontinue treatment as a result of such events, according to the report. In addition, neither extending treatment to 24 weeks nor adding ribavirin provided any clear benefit.

“We saw a cure rate of about 93% with only 12 weeks of treatment using an all-oral regimen that did not include interferon or ribavirin,” Lawitz said. “This is especially encouraging given the high proportion of participants who had multiple characteristics traditionally associated with low cure rates, including cirrhosis. This is the first trial combining two DAAs that are currently on the market and supports recent American Association for the Study of Liver Diseases/Infectious Disease Society of America (AASLD/IDSA) and the European Association for the Study of the Liver (EASL) treatment recommendations.”

In the other study, the HALLMARK-DUAL phase 3 study, led by Michael Manns, MD, from Hannover Medical School in Germany, 645 patients with HCV genotype 1b from 18 countries were randomly assigned to receive a 6-month course of treatment with a pair of oral DAAs asunaprevir and daclatasvir. Compared to a placebo control group, the regimen was effective and well tolerated, even in patients who have traditionally been the hardest to treat.

The authors report that 90% of previously untreated patients and 82% who were intolerant of treatment, or who had been treated unsuccessfully using standard regimens, were effectively cured. No differences in response were detected in patients with predictors of poor response to treatment, such as those who were male, older, African American, or who had advanced liver disease.

“The efficacy and safety of 24 weeks of daclatasvir plus asunaprevir represents a huge improvement on the first generation of protease inhibitor based triple therapies for HCV genotype 1b infection (up to 48 weeks of boceprevir or telaprevir in combination with PEG/RBV),” Manns pointed out. “This new all-oral interferon and ribavirin-free combination could provide a more effective, safer, shorter, and simpler treatment option for those traditionally hard-to-cure patients with cirrhosis or those who have failed to respond to existing therapies.”

Writing in a linked comment, Ed Gane, MBChB, MD, director of the New Zealand Liver Transplant Unit at Auckland City Hospital, suggests, “In the future, very-short-duration, all-oral DAA regimens should improve treatment uptake and success, and reduce the health burden from liver-related complications. When combined with targeted testing and treatment of populations who transmit infection (i.e., treatment as prevention), these DAA regimens might eventually eliminate HCV infection.”

Gane’s comments are entitled, “Hepatitis C beware—the end is nigh.”



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