Two experimental drugs that block a key enzyme in the replication of the hepatitis C virus promise to bring an improvement in therapy for infections with the virus comparable to the improvement in HIV therapy when protease inhibitors were added to drug cocktails for that disease in 1995, researchers said Wednesday.
The two drugs, called boceprevir and telaprevir, significantly increase the number of patients who achieve what is known as a sustained viral suppression — effectively, a cure — in patients being treated for the first time and those who did not respond to initial therapy or who suffered a relapse.
“This is opening up a new door” for treatment of hepatitis C, said Dr. Raymond Koff of the University of Connecticut School of Medicine in Farmington, who was not involved in the research. Both drugs are likely to be approved by the Food and Drug Administration in May and, “once these drugs are available, doctors are going to be overwhelmed” by patients demanding them, said Koff, who is on the board of directors of the Hepatitis Foundation International.
“What’s particularly exciting about these medications is that they address a very big unmet need in hepatitis C, the efficacy of antiviral therapy in African Americans,” said Dr. Sammy Saab, a hepatitis specialist at UCLA’s Geffen School of Medicine who was not involved in the research.
Blacks respond much more poorly than whites to the existing treatments for hepatitis C, but the new drugs sharply reduce that disparity, he said. “This is a major breakthrough in treatment.”
The results of two clinical trials with boceprevir were reported Wednesday in two papers in the New England Journal of Medicine. Similar results with telaprevir were expected to be reported Thursday at a European liver meeting.
The hepatitis C virus was discovered only in 1989, but it has clearly been around for a long time. An estimated 3.2 million Americans are infected by it, typically by transmission through blood. Infections may initially be asymptomatic, but eventually they include debilitating fatigue, liver disease (including fibrosis and scarring) and liver cancer. There is no vaccine against the virus.
Current therapy for infections involves treatment with peginterferon and the antiviral drug ribavirin for up to a year. Response rates are about 50% at best for hepatitis C genotype 1, the most common and most difficult form of the virus.
In one of the two new trials reported in the New England Journal of Medicine, a team led by Dr. Fred Poordad of the Cedars-Sinai Medical Center in Los Angeles studied 1,097 patients with genotype 1 who had never been treated for hepatitis C. All were given the two standard drugs for four weeks. Then a third continued to receive only the standard drugs, while two other groups received different regimens of boceprevir in addition to the standard drugs.
Among patients receiving only the standard drugs, 38% had a sustained suppression of virus, compared with either 63% or 66% for the two different boceprevir regimens.
In the second trial, a team headed by Dr. Bruce R. Bacon of the Saint Louis University School of Medicine studied 403 hepatitis C patients who failed an initial round of therapy with the two standard drugs or who suffered a relapse, using the same design as in the first study.
Among patients receiving only the standard drugs, 21% had a sustained virus suppression, compared with 59% and 66% in the two boceprevir groups.
“There are still some problems, particularly side effects,” said Dr. James Ou, a hepatitis specialist at USC’s Keck School of Medicine, who was not involved in the study. The biggest side effect is anemia, which is caused by ribavirin and exacerbated by boceprevir. Many patients had to be given the drug erythropoietin to stimulate red blood cell production, and some dropped out of the trial because of the anemia.
The drug must also be taken three times a day.
“But if the patients can tolerate it, then the chance of them being cured is up to 70%...and that’s a very big improvement,” he said.
The trials were sponsored by Merck, which plans to sell the drug under the brand name Victrelis.