Duke University Medical Center
hepatitis C combination cleared the virus in 93 percent of patients
with liver cirrhosis who hadn’t previously been treated, according to a
study in the May 5, 2015, issue of The Journal of the American Medical Association.
Bristol-Myers Squibb funded the trial of the combination of three
drugs — daclatasvir, asunaprevir, and beclabuvir. None of the three
drugs are FDA-approved, but daclatasvir is currently under review by the
FDA. Duke Medicine researchers collaborated on the design and analysis
of the trial and authored the findings.
The trial recruited patients with hepatitis C-related cirrhosis, or
scarring of the liver, 112 of whom had not previously been treated for
hepatitis C, and 90 who had previous unsuccessful therapies. For those
with past failed therapies and potential resistance, the drugs were
slightly less successful, eliminating the virus in 87 percent.
However, for those with past failed therapies, incorporating a
fourth drug, ribavirin, appeared to enhance results. Ribavirin is a
commonly used hepatitis C treatment. When added to the investigational
regimen, success rates in previously treated patients reached 93 percent
— on par with those receiving treatment for the first time.
No vaccine has been developed to protect patients from the hepatitis
C virus, which is spread through blood and can lead to liver failure
and death if untreated. Most who are infected don’t know they have the
disease until they have symptoms and have already sustained liver
damage, said Andrew Muir, M.D., M.H.S., chief of the division of
gastroenterology at Duke and the study’s lead author. For this reason,
Americans born between 1945 and 1965 — baby boomers — should
automatically be tested, he urged.
For most of the past 20 years, therapies for hepatitis C relied on
interferon drugs, which require regular injections for as long as one
year and trigger miserable, flu-like side effects that prompt many
patients to quit the regimen. Some patients aren’t eligible for this
treatment if they have anemia, low platelets or other conditions, Muir
“Those with more advanced disease were unlikely to tolerate
interferons, and many patients would decide against even getting
treatment,” Muir said. “For those who could tolerate it, it was only
Since late 2013, several drug companies have released new,
interferon-free regimens. In many cases, these have proven to be more
effective than previous treatments.
“The development of interferon-free treatments has been a tremendous
step forward in the standard of care,” Muir said. “These drugs are
highly effective and well-tolerated by patients at all stages of liver
The trial was conducted between December 2013 and September 2014 at
nearly 50 sites across the United States, Canada, France, and Australia.
All patients were infected with genotype 1 hepatitis, a common strain
of the C virus in North America, Western Europe and Australia.
The drugs had minimal side effects for most participants. Nine
patients experienced serious adverse events three of which were
considered related to treatment, the study states.
Among the study’s limitations were the absence of a placebo group
that could pinpoint the sources of side effects, and a lack of racial
diversity, with 88 percent white participants. The study also did not
statistically distinguish the impact of the addition of ribavirin to
some participants’ daily regimen.
In addition to Muir, study authors include Fred Poordad; Jacob
Lalezari; Gregory Everson; Gregory J. Dore; Robert Herring; Aasim
Sheikh; Paul Kwo; Christophe Hézode; Paul J. Pockros; Albert Tran;
Joseph Yozviak; Nancy Reau; Alnoor Ramji; Katherine Stuart; Alexander J.
Thompson; John Vierling; Bradley Freilich; James Cooper; Wayne
Ghesquiere; Rong Yang; Fiona McPhee; Eric A. Hughes; E. Scott Swenson;
and Philip D. Yin.
Bristol-Myers Squibb sponsored the study. Muir received grant
funding from Bristol-Myers Squibb during the conduct of the trial, as
well as grant funding and personal fees from AbbVie, Achillion,
Bristol-Myers Squibb, Gilead, and Merck, personal fees from Theravance,
and grant funding from Roche outside of the work submitted for this JAMA article.