Reuters Health Information: High HCV response rates with daclatasvir/asunaprevir: phase III data
High HCV response rates with daclatasvir/asunaprevir: phase III data
Last Updated: 2014-08-06
By Anne Harding
NEW YORK (Reuters Health) - A combination of daclatasvir
plus asunaprevir yielded high rates of sustained virological
response (SVR) in treatment-naive patients with hepatitis C 1B
infection, including those with cirrhosis, in a multinational
phase III trial.
Response rates were nearly as high in patients who either
hadn't responded to peginterferon alfa (IFN) plus ribavirin,
could not tolerate the drug combination, or who were ineligible
to take it, according to Dr. Michael Manns of Hannover Medical
School in Hannover, Germany and colleagues.
They reported the findings online July 28 in The Lancet.
"In this study it really showed that there is almost no
significant side effects beyond the placebo," Dr. Manns told
Reuters Health in a telephone interview. "The drawback is that
it's a 24-week treatment."
Both drugs are being developed by Bristol-Myers Squibb and
are expected to be approved in the U.S. and Europe in September,
Dr. Manns said.
If the drug combination is approved, he noted, it will be
the first oral regimen including two direct-acting antiviral
agents (DAA) made by the same company. Daclatasvir would also be
the first non-structural protein 5A (NS5A) inhibitor to be
approved, Dr. Manns said. "Now with this drug we are able to
intervene with three different steps in the hepatitis C life
In the HALLMARK-DUAL study, Dr. Mann and colleagues at 116
sites in 18 countries enrolled 307 treatment-naive patients, 205
patients who had not responded to IFN and ribavirin, and 235
patients who were either medically ineligible for IFN and
ribavirin, could not tolerate the drug combination, or both. A
third of patients had cirrhosis.
Treatment-naive patients were initially randomized to
daclatasvir 60 mg once a day and asunaprevir 100 mg twice daily,
or placebo, for 12 weeks. Afterward, the patients in the
active-treatment group continued on the drug combination for 12
more weeks, while the placebo group patients were switched to a
different daclatasvir plus asunaprevir study.
Everyone else - i.e., the non-responders and ineligible,
intolerant, or ineligible/intolerant patients - received
open-label daclatasvir plus asunaprevir for 24 weeks.
Ninety percent of patients in the treatment-naive group had
a sustained virological response, as did 82% of the
non-responders and 82% of the ineligible/intolerant group, the
During the initial 12 weeks of the study, adverse event
rates and grade 3 or 4 laboratory abnormalities were similar for
the placebo and active-treatment groups. Rates of serious
adverse events were 6% in the treatment-naive group, 5% among
non-responders, and 7% in the ineligible/intolerant group.
Adverse events leading to discontinuation occurred in 3%, 1%,
and 1% of patients in each group, respectively.
Response rates were similar for patients with cirrhosis or
without cirrhosis, except in patients with significant portal
hypertension and thrombocytopenia, Dr. Manns noted.
Signature-resistance-associated variants (RAV)s in NS5A or
NS3 sequences were the only baseline predictors for treatment
failure in the HALLMARK-DUAL trial, Dr. Ed Gane of Auckland City
Hospital in New Zealand noted in an editorial accompanying the
"This association suggests that testing for these RAVs
should be done before asunaprevir plus daclatasvir are started
and that this regimen should be avoided in affected patients,"
Dr. Gane writes.
Several other DAAs have recently been approved or awaiting
approval, Dr. Gane noted. "When combined with targeted testing
and treatment of populations who transmit infection...these DAA
regimens might eventually eliminate HCV infection," he adds.
"The only barrier to achieving this goal will be the ability to
access these new therapies."
In developing countries with high rates of HCV, IFN-based
treatments may still be the treatment of choice, given the
costliness of DAAs, according to Dr. Gane. He concludes: "As
almost 75% of all patients with HCV infection reside in
economically deprived regions of eastern Europe, Asia, and the
Middle East, consideration should be given to discounting prices
in those regions. Eradication of HCV infection worldwide will
only be achievable through universal access to HCV testing and
new DAA regimens."