Hepatitis C treatment is about to get simpler and more effective, with more cures, no more weekly injections, reduced side effects, and many fewer pills, researchers say.
In a new study, combination treatments involving a pair of experimental oral antiviral drugs, daclatasvir and sofosbuvir, proved safe and highly effective in curing hepatitis C, a liver-damaging infectious disease that kills more Americans than HIV/AIDS.
The new combination worked well even in the hardest-to-treat patients, in whom the current conventional “triple drug therapy” has failed to cure the infection, the research team reports in the New England Journal of Medicine.
“This research paves the way for safe, tolerable and effective treatment options for the vast majority of those infected with hepatitis C,” says study leader Mark Sulkowski, medical director of the Johns Hopkins Center for Viral Hepatitis. “Standard treatments for the disease are going to improve dramatically within the next year, leading to unprecedented advances for the treatment of patients infected with the hepatitis C virus.”
98 percent of patients cured
The research involved 211 patients with any of the three major types of the disease, treated at one of 18 US medical centers.
Among patients with genotype 1—the most common strain in the United States—98 percent of 126 previously untreated patients and 98 percent of 41 patients whose infections remained even after the triple therapy were considered cured; they had no detectable virus in their blood three months after treatment stopped.
Results were similar in study participants infected with genotypes 2 or 3, strains that are less common in the United States.
The study participants took a daily combination of 60 milligrams of daclatasvir and 400 milligrams of sofosbuvir, with or without ribavirin (a medication that is part of the current triple therapy drug cocktail).
Only 1 or 2 pills a day
On Dec. 6, the US Food and Drug Administration approved sofosbuvir in combination with peginterferon, another part of the triple-drug regimen, and ribavirin for the treatment of genotype 1 infection. The agency also approved sofosbuvir in combination with only ribavirin for genotype 2 and 3 infection. Daclatasvir has not yet been approved by the FDA.
Sulkowski says that if daclatasvir and other new drugs for hepatitis C win approval from the FDA, patients’ dreaded weekly injections of peginterferon will be a thing of the past.
The so-called “pill burden” of what had been standard therapy for genotype 1 could go down from some 18 pills per day and one injection per week to as few as one or two pills per day and no injections, Sulkowski says. Side effects from the new pill combination were generally mild, but included fatigue, headache, and nausea. That, Sulkowski says, compares favorably with peginterferon-based therapy, tied to severe side effects that may include fatigue and depression.
The new study is one of the first to show that hepatitis C can be cured without the use of ribavirin, which is known to cause anemia.
The advent of simpler pill-only regimens, Sulkowski adds, should make it easier for those infected with hepatitis C to be cured, preventing the development of liver cancer and liver failure and obviating the need for liver transplant. Currently, he says, fewer than 5 percent of the estimated 3.2 million Americans with hepatitis C have been cured, according to the U.S. Centers for Disease Control and Prevention. The CDC also estimates that between 50 and 75 percent of people who live with chronic hepatitis C are unaware that they are infected.
Sulkowski says simpler treatment regimens could not come soon enough. Many people with the infection, mainly those born between 1945 and 1965, were infected during the 1970s and 1980s through injection drug use and tainted blood transfusions. Many of them now suffer from cirrhosis and liver cancer tied to chronic infection. This is why, he says, the CDC recommended hepatitis C screenings in 2012 for all baby boomers.
Sulkowski says that further research is being performed by Gilead Sciences of Foster City, Calif., on a regimen that combines sofosbuvir with another experimental drug it manufactures, called ledipasvir, into a single once-a-day tablet. Ledipasvir is similar to daclatasvir, made by Bristol-Myers Squibb of Princeton, NJ. The combination of sofosbuvir and ledipasvir has not yet been approved by the FDA.
Gilead Sciences and Bristol-Myers Squibb funded the study. Sulkowski is a paid consultant to both; the terms of his arrangements are managed by Johns Hopkins University in accordance with its conflict of interest policies.
Besides Johns Hopkins, investigators involved in this study were from the Fundacion de Investigacion in San Juan, Puerto Rico; the University of Pennsylvania; Southern California Liver Center in Coronado, Calif.; Weill Cornell Medical College in New York; the University of Texas Southwestern Medical Center in San Antonio; the University of Michigan; Orlando Immunology Center in Florida; Mercy Medical Center in Baltimore; Miami Research Associates in Florida; the University of Florida; and the University of Colorado Denver.
Source: Johns Hopkins University