EDP-514 is Safe and Well-Tolerated up to 800
mg
Robust Antiviral Activity Demonstrated in
Chronic Hepatitis B Virus Patients at All Doses
Enanta Pharmaceuticals, Inc. (NASDAQ: ENTA), a clinical-stage
biotechnology company dedicated to creating small molecule drugs
for viral infections and liver diseases, today announced final
Phase 1b data for EDP-514, a novel pangenotypic class II hepatitis
B virus (HBV) core inhibitor, in conjunction with two posters
presented at The Liver Meeting® 2021, hosted by the American
Association for the Study of Liver Diseases (AASLD).
“We are excited to present final data for EDP-514 from our Phase
1b studies in viremic and NUC-suppressed chronic HBV patients,
giving us continued confidence in EDP-514 as a potential treatment
for HBV,” said Jay R. Luly, PhD, President and Chief Executive
Officer of Enanta Pharmaceuticals. “At 800 mg, EDP-514 continues to
demonstrate that it is safe and well-tolerated up to 28 days when
dosed alone or in combination with NUC, as shown in the
NUC-suppressed patients. Importantly, EDP-514 has robust antiviral
activity across all dose groups, as best illustrated in the viremic
patients where up to a 3.5 log decline in HBV DNA was observed.
These data are supportive of a once-daily oral dosing regimen that
could provide a foundation for a combination therapy approach to
achieve functional cures for chronic HBV patients.”
822: “EDP-514, a Novel Pangenotypic Class II Hepatitis B Virus
Core Inhibitor: Results of a 28-day Phase 1b Study in
NUC-Suppressed CHB Patients” Jordan J. Feld, MD, MPH, Toronto
Centre for Liver Disease, University Health Network, Toronto,
Canada
The poster highlights data from Part 2 of a Phase 1a/1b
randomized, double-blind, placebo-controlled study assessing the
safety, tolerability, pharmacokinetics and antiviral activity of
three doses of EDP-514 in 24 NUC-suppressed chronic HBV patients
who were either HBeAg-positive or HBeAg-negative. Patients were
randomized to receive 200 mg (n=6), 400 mg (n=6), 800 mg (n=6) of
EDP-514 or placebo (n=6) daily for 28 days.
Overall, EDP-514 was generally safe and well-tolerated at 200
mg, 400 mg, and 800 mg doses for 28 days. EDP-514 was rapidly
absorbed and its exposure increased with increasing multiple doses.
EDP-514 exhibited pharmacokinetics suitable for once daily oral
dosing, with Ctrough concentrations reaching up to ~20-fold above
the protein-adjusted EC50. At Day 28, mean HBV RNA changes of
-0.81, -1.12, 0.10, and -0.19 logs were observed in the 200 mg, 400
mg, 800 mg and placebo groups, respectively. EDP-514 led to a
maximum HBV RNA reduction of 2.3 log in HBeAg-negative and 2.8 log
in HBeAg-positive subjects in EDP-514 arms compared to 1.2 log in
the placebo arm. In the EDP-514 800 mg arm, five of six subjects
had either non-detectable or very low levels of HBV RNA at
baseline; consequently, the effect of EDP-514 on HBV RNA could not
be assessed in these subjects. As expected in this NUC-suppressed
patient population, there were no discernible changes in HBV DNA,
HBeAg, HBcrAg, and HBsAg, and no instances of virologic failure
were reported.
823: “EDP-514, a Novel Pangenotypic Class II Hepatitis B Virus
Core Inhibitor Demonstrates Significant HBV DNA and HBV RNA
Reductions in a Phase 1b Study in Viremic, Chronic Hepatitis B
Infected Patients” Man Fung Yuen, MBBS, MD, PhD, DSc, Department of
Medicine, Queen Mary Hospital, The University of Hong Kong, Hong
Kong.
Data in this poster details results from a randomized,
double-blind, placebo-controlled Phase 1b study evaluating the
safety, pharmacokinetics and antiviral activity of three doses of
EDP-514 in viremic chronic HBV patients, 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.
Results demonstrated that EDP-514 was safe and well-tolerated
through 28 days of treatment, displayed pharmacokinetics supportive
of once-daily dosing, and resulted in mean HBV DNA reductions of
2.9, 3.3, and 3.5 logs at 28 days for the 200 mg, 400 mg, and 800
mg cohorts, respectively, compared to 0.2 log in placebo. HBV RNA
was undetectable at Day 28 in 11 patients in the three EDP-514
cohorts as compared to none in placebo. Mean HBV RNA reductions
were 2.9, 2.4, and 2.0 logs for the 200 mg, 400 mg, and 800 mg
cohorts, respectively, compared to 0.02 log in placebo.
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 covalently-closed circular DNA
(cccDNA) in primary human hepatocytes when given early during HBV
infection. In vitro data also show that EDP-514 is pangenotypic,
and that combinations of EDP-514 with a nucleoside reverse
transcriptase inhibitor (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 currently in
development for the following disease targets: respiratory
syncytial virus (RSV), hepatitis B virus (HBV) and SARS-CoV-2
(COVID-19). Enanta is also conducting research in 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 June 30, 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.
1. Polaris Observatory Collaborators. “Global prevalence,
treatment, and prevention of hepatitis B virus infection in 2016: a
modelling study.” The Lancet. Gastroenterology & Hepatology
vol. 3,6 (2018): 383-403. doi:10.1016/S2468-1253(18)30056-6 2. Woo,
Aaron Shu Jeng et al. “Alpha-interferon treatment in hepatitis B.”
Annals of Translational Medicine vol. 5,7 (2017): 159.
doi:10.21037/atm.2017.03.69 3. Yeo, Yee Hui et al. “Factors
Associated with Rates of HBsAg Seroclearance in Adults with Chronic
HBV Infection: A Systematic Review and Meta-analysis.”
Gastroenterology vol. 156,3 (2019): 635-646.e9.
doi:10.1053/j.gastro.2018.10.027
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Media and Investor Contact Jennifer Viera 617-744-3848
jviera@enanta.com
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