One new trial, of 1,097 patients with hepatitis C genotype 1 who had never been treated, found that after 24 or 44 weeks of adding boceprevir to their drug regimen some two-thirds of non-black patients showed they were effectively suppressing the virus. The drug combo was not as effective for black patients, who are less likely to have a gene alteration that is linked to responsiveness to one of the drugs. But adding boceprevir still boosted response rates in these patients from 23 percent to more than half in the 44-week treatment group.
In the other trial, 403 patients with the disease who had not responded to traditional treatment—either showing no improvement or relapsing—were studied. Adding boceprevir to the standard treatment for 32 or 44 weeks resulted in sustained viral response rates in 59 and 66 percent of patients, respectively, compared with 38 percent in the control group.
The studies were both somewhat unusual in that they started patients out with a month-long lead-in period in which patients received the two drugs already available—before boceprevir was introduced to some groups. This "allowed some prediction capability of both subsequent response as well as risk of developing resistant variants," Jensen explains.
Early studies showed that although a protease inhibitor given on its own was very effective initially, it often led to resistant strains of the virus in a matter of days, Gordon says. Even with interferon and ribavirin, resistance "remains a concern," he says. To keep it to a minimum, "clinicians must follow such patients very closely during therapy because if the viral level starts to rise after initially declining, then the protease inhibitor must be stopped to prevent the development of even more resistant strains."
Potosky notes that the extent of resistance will only become clear with time—and as more people take the new drugs. And just as they monitor HIV patients for telltale resistance patterns, doctors should be able to detect early signs of resistance in people being treated for hepatitis C as well.
Adding boceprevir also increased the amount of side effects patients experienced. More than 40 percent of subjects taking this third drug required treatment for anemia in one of the studies, and in the other, severe anemia led doctors to decrease dosage in some 20 percent of subjects. Even though some of these cases were serious, few patients dropped out of treatment.
With boceprevir and telaprevir likely in the home stretch to reach potentially millions of hepatitis C patients in the U.S., doctors and researchers are now turning their focus to the many challenges that remain.
Aside from keeping resistance low and dialing down side effects, the next steps are to try to simplify the treatment regimen. "Everyone wants to get rid of interferon and ribavirin because both have toxicity that make them often difficult to tolerate," Gordon notes. Interferon also currently is usually administered via injection, so moving to an all-oral, once-a-day dosing would make treatment better and more consistent.
Gordon also looks forward to finding ways to help special populations of patients, including those who have HIV, end-stage liver disease or renal disease, as well as children, "who are currently not eligible for our current therapies."