The
NDA contains data to support approval for daclatasvir in
combination with sofosbuvir; would be the first 12-week regimen
specifically for the treatment of hepatitis C genotype 3
The
application is based on a Phase III clinical trial which tested a
12-week, ribavirin-free regimen and resulted in sustained
virologic response (SVR12) in 90% of treatment-naïve and 86% of
treatment-experienced genotype 3 HCV patients
PRINCETON, N.J.--(
BUSINESS WIRE)--
Bristol-Myers
Squibb Company (NYSE:BMY) announced today that the resubmitted new
drug application (NDA) for daclatasvir, an investigational NS5A
replication complex inhibitor, has been accepted for review by the U.S.
Food and Drug Administration (FDA) for use in combination with
sofosbuvir for the treatment of chronic hepatitis C (HCV) genotype 3.
The original NDA has been amended to include data from the Phase III
ALLY-3 trial, which showed high cure rates for the combination, with
sustained virologic response 12 weeks after treatment (SVR12) in 90% of
treatment-naïve and 86% of treatment-experienced genotype 3 HCV
patients. SVR12 rates were higher (96%) in non-cirrhotic genotype 3
patients, regardless of treatment history. The FDA will now review the
submission within a six-month timeframe.
“The daclatasvir-based NDA seeks to address a high-unmet patient need
that still exists despite recent hepatitis C treatment advances.
Approximately 9-12% of HCV patients in the U.S. have genotype 3. That’s
thousands of individuals in the U.S. who historically have had limited
treatment options requiring at least 24 weeks of treatment,” said
Douglas Manion, M.D., head of Specialty Development, Bristol-Myers
Squibb. “We also are continuing clinical trials to determine the
potential of daclatasvir-based regimens in treating a range of other
high unmet-need patients, including those coinfected with HIV, HCV
patients with decompensated cirrhosis, and HCV recurrence in
post-transplant patients.”
Genotype 3 is estimated to affect 54.3 million people worldwide, and is
the second most common hepatitis C genotype after genotype 1 (83.4
million). The more aggressive nature of genotype 3 lies in the damage it
causes to the liver, as it is associated with progressive disease,
increased rates of steatosis and a disproportionately increased risk of
hepatocellular carcinoma.
In the ALLY-3 study, the daclatasvir and sofosbuvir combination regimen
was well tolerated, with no deaths, treatment-related serious adverse
events, or discontinuations due to adverse events. The most frequent
side effects (≥5%) were headache (19.7%), fatigue (19.1%), nausea
(11.8%), diarrhea (8.6%), insomnia (5.9%), abdominal pain and arthralgia
(both 5.3%). Additionally, there were 17 (11.2%) treatment failures,
with 16 relapses post-treatment and 1 rebound at the end of treatment.
There were no viral breakthroughs in this ribavirin-free regimen.
About ALLY-3: Study Design
This Phase III open-label clinical trial enrolled 152 genotype 3 HCV
patients; 101 treatment-naïve patients and 51 treatment-experienced
patients in 2 cohorts each received daclatasvir 60 mg and sofosbuvir 400
mg once daily for 12 weeks, with 24 weeks of follow-up. The primary
endpoint was SVR12 rates, defined as HCV RNA < LLOQ target detected or
not detected at follow-up week 12 in treatment-naïve and
treatment-experienced patients.
Read complete press release here