Expect miracles: New drug for hepatitis C may put treatment in the hands of primary care
AT THE ANNUAL INTERNAL MEDICINE PROGRAM
Other oral DAAs in the developmental pipeline include simeprevir, daclatasvir, and asunaprevir. The clinical trials experience to date demonstrate that combination therapy with more than one DAA boosts the cure rate even higher than with sofosbuvir/ribavirin. For example, in the phase II, open-label AVIATOR study, 12 weeks of a cocktail comprising three DAAs plus ribavirin brought a 96% cure rate in treatment-naive patients with HCV genotype 1 and a 93% cure rate in those who had previously failed on standard interferon-containing therapy. The AVIATOR cocktail is being formulated as a two-pills-per-day regimen.
Further, Dr. Everson was principal investigator in a Bristol-Myers Squibb–sponsored study of a totally interferon- and ribavirin-free regimen consisting of triple-DAA therapy. Each of the DAAs has a different mechanism of action: Daclatasvir is an inhibitor of the HCV NS5a protein; asunaprevir is an NS3 protease inhibitor; and the agent known for now as BMS-791325 is a nonnucleoside polymerase NS5b inhibitor. The cure rate with 12 weeks of triple-DAA therapy in treatment-naive, noncirrhotic patients with HCV genotype 1 was 94%.
Hepatologists define cure of HCV as an SVR12, or a sustained virologic response featuring no detectable HCV RNA in the blood for 12 weeks after the conclusion of therapy. The likelihood that a patient who achieves an SVR12 will remain HCV free through 10 years is 99%-100% (Gastroenterology 2010;139:1593-1601).
"The future looks pretty good for hepatitis C patients," Dr. Everson observed.
Moreover, curing HCV is going to have major downstream benefits for the health care system, he added. Today, 36% of all patients on the liver transplantation waiting list have HCV; that proportion will drop substantially. There will be fewer cases of hepatocellular carcinoma, B-cell lymphoma, and adult-onset diabetes, a drop in HCV-related autoimmune disorders, and reduced costs of care for patients with chronic HCV.
Dr. Everson reported that he receives research grants from and/or serves as a consultant to or advisory board member for roughly two dozen pharmaceutical companies.
