Enanta Pharmaceuticals Reports Positive Data from Phase 1b Study of EDP-514, a Hepatitis B Virus (HBV) Core Inhibitor, in Vir...
June 22 2021 - 4:01PM
Business Wire
Positive 28-Day Data from First Two EDP-514
Dose Cohorts: 200 mg and 400 mg
EDP-514 was Safe and Well-Tolerated with
Pharmacokinetics Supportive of Once-Daily, Oral Dosing
Patients Dosed with 400 mg EDP-514 Showed a
Mean Reduction of 3.3 Logs in HBV DNA
Enanta Pharmaceuticals, Inc. (NASDAQ:ENTA), a clinical stage
biotechnology company dedicated to creating small molecule drugs
for viral infections and liver diseases, today announced positive
data from the first two dose cohorts of its Phase 1b study of
EDP-514 in viremic chronic HBV patients who were not being treated
with a nucleoside reverse transcriptase inhibitor (NUC). The data
demonstrated that EDP-514, Enanta’s novel class II oral HBV core
inhibitor, was safe and well-tolerated through 28 days of
treatment, displayed pharmacokinetics (PK) supportive of once-daily
dosing, and resulted in mean HBV DNA reductions of 2.9 and 3.3 logs
at 28 days for the 200 mg and 400 mg cohorts, respectively.
“We are extremely pleased with these promising clinical results
for EDP-514, which are comparable to the best antiviral effects
reported for any core inhibitor to date and also extend the
compound’s excellent safety and tolerability profile,” said Jay R.
Luly, Ph.D., President and Chief Executive Officer of Enanta
Pharmaceuticals. “In particular, we are encouraged by the rapid and
robust declines in HBV DNA, which position EDP-514 to be a key
component of a combination regimen for HBV. We believe EDP-514, in
combination with a NUC and other mechanisms, could provide a
foundation for an all-oral treatment approach to achieve functional
cures in patients with chronic HBV infection. We look forward to
progressing EDP-514 in combination with our oral HBV RNA
destabilizer, EDP-721, a compound that has demonstrated significant
reductions in HBsAg preclinically and which we expect to advance
into the clinic mid-year. Ultimately, our all-oral, triple
combination approach could provide potent suppression of multiple
key steps in HBV replication, including HBV DNA, HBV RNA and HBsAg,
to achieve our goal of developing a functional cure for HBV
patients.”
The randomized, double-blind, placebo-controlled Phase 1b study
is evaluating the safety, pharmacokinetics, and antiviral activity
of three doses of EDP-514 in viremic patients with chronic HBV
infection, either HBeAg-positive or HBeAg-negative, and without
cirrhosis. Patients were randomized to receive 200 mg (n=6), 400 mg
(n=6), or 800 mg (n=6) of EDP-514 or placebo (n=6) daily for 28
days with an 8-week follow-up period. The 800 mg cohort is ongoing
and final study results will be presented at a future scientific
conference.
Of the sixteen patients randomized in the first two dose cohorts
(6 active and 2 placebo per cohort), majorities were male (56%),
Asian (100%) and HBeAg-negative (94%), with a mean age of 45 years,
mean baseline HBV DNA of 4.87 logs IU/mL, and mean baseline HBV RNA
of 3.45 logs IU/mL. Overall, six patients reported treatment
emergent adverse events (TEAEs) and all were mild except for 4
moderate events (2 in placebo and 2 in the 200 mg cohort) both of
which were considered unlikely related to drug. No grade 3 TEAEs or
serious adverse events, grade 3/4 clinical laboratory
abnormalities, ALT/AST elevations or clinically relevant
electrocardiogram (ECG) or vital sign changes were observed in the
EDP-514 groups. EDP-514 exposure increased linearly with dose, with
concentrations up to approximately 20-fold the protein-adjusted
EC50 (9-fold for 200 mg, 20-fold for 400 mg).
At Day 28, mean reductions in HBV DNA were 2.9, 3.3, and 0.2
logs IU/mL in the 200 mg, 400 mg and placebo groups, respectively,
with a maximum reduction of 4.2 logs vs. 0.5 log in placebo. HBV
DNA was below the lower level of quantitation (LLOQ) in 4 patients
treated with EDP-514 compared to none in the placebo group. Mean
HBV RNA reductions of 2.9, 2.4 and 0.3 logs IU/mL were observed in
the 200 mg, 400 mg and placebo groups, respectively, with a maximum
reduction of 4.8 logs vs. 1.9 logs in placebo. HBV RNA was
undetectable at Day 28 in 8 patients treated with EDP-514 vs. none
in placebo. As expected, no clinically significant changes in
levels of HBsAg, HBeAg, or HBcrAg were observed.
About EDP-514
EDP-514 is Enanta’s lead HBV core inhibitor candidate. Core
inhibitors, also known as capsid assembly modulators or core
protein allosteric modulators, are a novel class of HBV replication
inhibitors that have been shown to act at multiple steps in the HBV
lifecycle. Preclinical data demonstrate that EDP-514 is a potent
inhibitor of HBV replication and prevents the de novo formation of
new HBV cccDNA in primary human hepatocytes when given early during
HBV infection. In vitro data also show that EDP-514 is
pan-genotypic, and that combinations of EDP-514 with a NUC, the
current anti-viral therapy for HBV, or with a class I core
inhibitor, result in additive to synergistic antiviral effects. ln
vivo models of EDP-514 demonstrate excellent efficacy with a
greater than 4-log viral load reduction in HBV-infected PXB
mice.
About Hepatitis B Virus
Hepatitis B is a viral infection that attacks the liver and can
cause both acute and chronic disease. The virus is most commonly
transmitted from mother to child during birth and delivery, as well
as through contact with blood or other body fluids. It is estimated
that over 290 million people worldwide have chronic HBV infection.1
Current approaches to treatment include interferon therapy and/or
NUCs. Treatment with interferon offers poor cure rates and is
accompanied by serious side effects.2 NUCs can be very effective at
suppressing the virus but rarely result in full eradication of the
virus from the liver.3
About Enanta
Enanta is using its robust, chemistry-driven approach and drug
discovery capabilities to become a leader in the discovery and
development of small molecule drugs for the treatment of viral
infections and liver diseases. Enanta’s research and development
efforts have produced clinical candidates for the following disease
targets: respiratory syncytial virus (RSV), hepatitis B virus (HBV)
and non-alcoholic steatohepatitis (NASH). Enanta is also conducting
research in SARS-CoV-2 (COVID-19) and human metapneumovirus
(hMPV).
Enanta’s research and development activities are funded by
royalties from hepatitis C virus (HCV) products developed under its
collaboration with AbbVie. Glecaprevir, a protease inhibitor
discovered by Enanta, is sold by AbbVie in numerous countries as
part of its leading treatment for chronic HCV infection under the
tradenames MAVYRET® (U.S.) and MAVIRET® (ex-U.S.)
(glecaprevir/pibrentasvir). Please visit www.enanta.com for more
information.
Forward Looking Statements Disclaimer
This press release contains forward-looking statements,
including statements with respect to the prospects for further
development of EDP-514 for HBV. Statements that are not historical
facts, are based on management’s current expectations, estimates,
forecasts and projections about Enanta’s business and the industry
in which it operates and management’s beliefs and assumptions. The
statements contained in this release are not guarantees of future
performance and involve certain risks, uncertainties and
assumptions, which are difficult to predict. Therefore, actual
outcomes and results may differ materially from what is expressed
in such forward-looking statements. Important factors and risks
that may affect actual results include: the risks of early stage
development efforts in the disease areas in Enanta’s research and
development pipeline, such as HBV; the impact of development,
regulatory and marketing efforts of others with respect to
competitive treatments for HBV; Enanta’s limited clinical
development experience; Enanta’s need to attract and retain senior
management and key scientific personnel; Enanta’s need to obtain
and maintain patent protection for its product candidates and avoid
potential infringement of the intellectual property rights of
others; and other risk factors described or referred to in “Risk
Factors” in Enanta’s most recent Form 10-Q for the quarter ended
March 31, 2021 and other periodic reports filed more recently with
the Securities and Exchange Commission. Enanta cautions investors
not to place undue reliance on the forward-looking statements
contained in this release. These statements speak only as of the
date of this release, and Enanta undertakes no obligation to update
or revise these statements, except as may be required by law.
1https://pubmed.ncbi.nlm.nih.gov/29599078/
2https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5401664/
3https://pubmed.ncbi.nlm.nih.gov/30342034/
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Media and Investor Contact Jennifer Viera 617-744-3848
jviera@enanta.com
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