A Second Hepatitis C Antiviral Moves Closer to Approval
by Larry Buhl
Fast on the heels of the successful Phase III trial of telapravir, covered in the October 2010 issue, another hepatitis C (HCV) protease inhibitor has passed the final hurdle before heading to the FDA for approval.
Merck Research Laboratories studied its drug boceprevir, in combination with traditional hepatitis meds Pegintron (peginterferon alfa-2b) and Rebetol (ribavirin USP) in two Phase III studies to evaluate how effectively the protease inhibitor cleared the virus from the blood and how much shorter treatment could be when using boceprevir.
The standard treatment for hepatitis C is a forty-eight-week regimen of pegylated interferon, which boosts the immune system, and the antiviral agent ribavirin, which is a general-purpose antiviral agent. But this treatment cures less than half of those who receive it. The most difficult strain to treat is genotype 1, which infects about seventy percent of Americans living with HCV.
Like telapravir, boceprevir is a direct acting antiviral, which means it attacks the virus itself. Both treatment-naïve (previously untreated patients) and treatment-failing (patients who had previously failed hepatitis C virus therapy) patients benefited by taking boceprevir.
“Boceprevir is a game changer in the treatment of hepatitis C,” Dr. Clifford Brass, executive director in Merck Research Laboratories, and lead researcher on boceprevir’s Phase III trial told A&U. “[With boceprevir] the number of patients with sustained virologic response has grown from less than a majority of patients [on traditional medication] to more like nearly seventy percent with boceprevir. That’s a big step up. And although the risk-benefit assessment is different for every patient, doctors will be able to say that a patient has at least a sixty percent chance of being cured by using boceprevir.”
Unlike with HIV, protease inhibitors like telapravir and boceprevir have the ability to cure patients of the hepatitis C virus. Sustained virologic response, or SVR, is the holy grail of treating viruses, meaning there is no detectable virus in the blood six months after therapy is stopped.
Response-guided therapy (RGT) was studied in the boceprevir trials, meaning that for patients who met the early response criteria (a certain decrease in viral load in their blood at treatment week eight), they had the potential to stop all therapy early. When the two pivotal Phase III studies were reported at the recent American Association for the Study of Liver Diseases (AASLD) meeting in November, researchers reported that nearly half of all patients in the boceprevir RGT arms of these studies met early response criteria and received a shorter total duration of therapy.
In the RGT arm of the RESPOND-2 study (treatment-failing patients), forty-six percent met the early response criteria and were eligible to stop all treatment at thirty-six weeks, which is twelve weeks shorter than current standard therapy. In these patients, the SVR rate was eighty-six percent. It’s important to note that the RESPOND-2 study is the only study to evaluate a strategy for shorter treatment in patients who had failed previous hepatitis C virus therapy.
In the RGT arm of the SPRINT-2 study (treatment-naïve patients), forty-four percent met the early response criteria and were eligible to stop all treatment at twenty-eight weeks, which is twenty weeks shorter than current standard therapy duration. In these patients, the SVR rates were ninety-seven percent in non-African-American/non-Black treatment-naïve patients and eighty-seven percent in African-American/Black treatment-naïve patients.
The differing response rates between the races can be explained by a genetic marker for interleukin 28B, Dr. Brass says. HCV-1 patients are genotyped as CC, CT, and TT. Studies have shown that African-American/Black patients have a lower response to hepatitis C virus treatment than non-African-American/Black patients because Black patients are more likely to be CT or TT. The SPRINT-2 study specifically studied Black patients as a separate cohort.
Dr. Brass believes the success of boceprevir can change how healthcare practitioners treat patients with HCV, a leading cause of cirrhosis and liver cancer. Additionally, Dr. Brass also pointed out that boceprevir was studied to assess the potential to reduce total treatment duration for both treatment-naïve and treatment-failing patients. “By adding boceprevir to the treatment regimen, patients can avoid continuing unnecessary therapy because their doctors will be able to learn who is responding to therapy early in the process.”
The goal, says Dr. Brass and other experts, is to eventually phase out the use of interferon in the treatment of hepatitis. The side effects of that drug are well known to be strong and sometimes debilitating, leading many to refuse treatment or stop it before it’s effective.
Merck has initiated the submission of a new drug application for boceprevir in the U.S. to the FDA on a rolling basis. A spokesperson for Merck said the company was expecting to complete regulatory submissions in both the U.S. and the European Union as we went to press.
Larry Buhl wrote about the Be Smart with Body Art campaign in the December 2010 issue