- Study Did Not Meet Primary Endpoint of Clinical Symptom
Reduction or Secondary Antiviral Endpoints
- Statistically Significant Percent of Subjects Who Received
EDP-938 Achieved Undetectable RSV RNA at End of Treatment
- EDP-938 was Safe and Well-Tolerated
- EDP-938 Continues to be Evaluated in Ongoing and Planned
Clinical Studies in High-Risk Populations
Enanta Pharmaceuticals, Inc. (NASDAQ: ENTA), a clinical-stage
biotechnology company dedicated to creating small molecule drugs
for viral infections and liver diseases, today reported topline
results for RSVP, its Phase 2b study evaluating EDP-938, a potent
N-protein inhibitor, in otherwise healthy adults with
community-acquired RSV. In this low-risk patient population which
had mild, self-resolving upper respiratory tract infection, EDP-938
did not meet the primary endpoint of reduction in total symptom
score compared to placebo, or the secondary antiviral endpoints.
However, a statistically significant difference in the number of
subjects achieving undetectable RSV RNA at the end of treatment at
Day 5 was observed with EDP-938 compared to placebo (p=0.033).
Further, EDP-938 demonstrated a favorable safety profile,
consistent with that observed in approximately 500 subjects exposed
to date. Enanta continues to evaluate EDP-938 in high-risk
populations in ongoing and planned clinical studies, including
pediatric patients, adult hematopoietic cell transplant recipients,
and a high-risk adult population, all of which have the most
significant unmet need.
“While RSVP did not meet the study endpoints, we are pleased to
observe a statistically significant difference in the number of
subjects achieving undetectable RSV RNA at the end of treatment
with EDP-938, making this the only study that has demonstrated a
statistically significant antiviral effect in an otherwise healthy
adult population with community-acquired RSV. The effect on RSV RNA
viral load is consistent with EDP-938’s mechanism of action of
inhibiting viral replication,” said Jay R. Luly, President and
Chief Executive Officer of Enanta Pharmaceuticals. “Although
patients were treated within 48 hours of symptom onset, a key
observation in this study was that the viral load and symptoms had
already peaked and were declining at the time of the first dose,
indicating RSV infection resolves quickly in this otherwise healthy
population.”
Dr. Luly added, “We continue to believe that RSV antiviral
treatment, including EDP-938, has the greatest potential to show
optimal efficacy in high-risk populations, as these patients have
reduced RSV immunity which manifests in a higher and longer
duration of viral load and greater disease severity, allowing a
bigger window to realize the full potential of EDP-938. Moving
forward, our broad clinical development plan is focused on
evaluating EDP-938 in populations with the greatest unmet need,
namely those who are at high-risk for severe disease, and we look
forward to providing further updates on our ongoing and planned
clinical studies.”
EDP-938 RSVP Phase 2b Study Topline Results
RSVP was a Phase 2b, randomized, double-blind, multicenter,
placebo-controlled study in ambulatory adults with or without
comorbidities aged 18 to 75 years with confirmed RSV infection
within 48 hours of symptom onset. Patients were randomized 1:1 to
receive once-daily 800 mg EDP-938 or placebo for 5 days and
followed until Day 14. The primary objective of the study was to
evaluate the effect of EDP-938 on progression of RSV infection by
assessment of clinical symptoms measured over the 14-day study
period. The secondary objectives evaluated the antiviral efficacy,
safety, and pharmacokinetics of EDP-938.
A total of 81 patients were randomized and dosed and included in
the intent-to-treat (ITT) analysis. The modified ITT efficacy
analysis included only the 66 patients (33 in each group) that were
subsequently confirmed to be RSV positive using a central RT-PCR
test. Demographics and baseline characteristics were well balanced
between the two arms, except for the median RSV viral load (5.9 and
7.1 log10 copies/mL, in EDP-938 and placebo, respectively).
Overall, most of the patients were female, White, non-Hispanic,
young (median age approximately 50 years old) and had a normal
frailty scale score, consistent with a healthy population as per
the eligibility criteria of the study. Only eight patients were 65
years or older (n=3 in EDP-938, n=5 in placebo), and a total of
seven patients (n=4 in EDP-938, n=3 in placebo) had stable asthma
and/or chronic obstructive pulmonary disease (COPD), at entry.
The primary endpoint, total symptom score (TSS) area under the
curve (AUC) from Day 1 through Day 14, was not met. The AUC for the
mean total symptom score (days x score) was not statistically
different between the two groups (p=0.256). Although, the secondary
antiviral endpoints were not met, a trend in favor of EDP-938 was
observed with regard to the percentage of subjects achieving
undetectable RSV RNA, with a statistically significant difference
observed at the end of treatment at Day 5 (p=0.033).
A total of 11 (~27%) patients in both the EDP-938 and placebo
arms reported treatment-emergent-adverse events. Most of the
adverse events (AEs) were mild and not related to study drug. There
were no severe or serious AEs, and no discontinuations due to AEs.
In the study, the observed safety profile was consistent with
previous clinical studies. Good EDP-938 exposures were achieved and
were consistent with those observed in treated subjects in previous
studies.
Data from RSVP will be presented at a future medical meeting or
in a peer-reviewed publication.
EDP-938 and RSV Clinical Development Program Next
Steps
Recruitment is ongoing for RSVPEDs, a Phase 2 randomized,
double-blind, placebo-controlled study in hospitalized and
non-hospitalized pediatric RSV patients, and RSVTx, a Phase 2b,
randomized, double-blind, placebo-controlled study in adult
hematopoietic cell transplant recipients with acute RSV infection
and symptoms of upper respiratory tract infection. The company
expects these studies to continue into 2023. Further, the company
plans to initiate an additional Phase 2b study in a high-risk adult
population, including the elderly and/or those with asthma, COPD,
or congestive heart failure, by year-end. Finally, Enanta is on
track to initiate a Phase 1 study for EDP-323, a novel, oral,
direct-acting antiviral selectively targeting the RSV L-protein, in
the second half of 2022. EDP-323 has shown sub-nanomolar potency
against RSV-A and RSV-B in vitro and is not expected to have cross
resistance to other classes of inhibitors. EDP-323 could be used as
a monotherapy or in combination with other RSV mechanisms, such as
EDP-938, to potentially broaden the addressable patient populations
or their treatment windows.
About EDP-938
EDP-938, Enanta’s lead N-protein inhibitor, is being developed
for the treatment of RSV infection, and has been granted Fast Track
designation by the U.S. Food and Drug Administration. EDP-938 is a
nanomolar inhibitor of both RSV-A and RSV-B activity. EDP-938 is
differentiated from RSV fusion inhibitors as the N-protein
inhibitor targets the virus’ replication machinery and has
demonstrated a high barrier to resistance in vitro. In preclinical
studies, EDP-938 maintained antiviral potency across all clinical
isolates tested and was active against viral variants resistant to
other mechanisms. EDP-938 demonstrated a favorable safety,
pharmacokinetic and drug-drug interaction profile in an extensive
Phase 1 program. In a Phase 2 challenge study, EDP-938 achieved
highly statistically significant (p<0.001) reductions in RSV
viral load and clinical symptoms compared to placebo, and was safe
and well-tolerated with infrequent AEs. EDP-938 is currently being
evaluated in RSVPEDs, a Phase 2 study in pediatric RSV patients,
and RSVTx, a Phase 2b study in adult hematopoietic cell transplant
recipients with RSV.
About Respiratory Syncytial Virus
RSV is the most common cause of bronchiolitis (inflammation of
the small airways in the lung) and pneumonia in children under one
year of age in the U.S. and a significant cause of respiratory
illness in older adults and immunocompromised individuals.1
According to the Centers for Disease Control and Prevention,
virtually all children in the United States get an RSV infection by
the time they are two years old and one to two out of every 100
children younger than six months of age with RSV infection may need
to be hospitalized.2 Globally, there are an estimated 33 million
cases of RSV annually in children less than five years of age, with
about 3 million hospitalized and up to approximately 120,000 dying
each year from complications associated with the infection.3 RSV
represents a significant health threat for adults older than 65
years of age, with an estimated 177,000 hospitalizations and 14,000
deaths associated with RSV infections annually in the United
States.4
About Enanta Pharmaceuticals, Inc.
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
programs include clinical candidates currently in development for
the following disease targets: respiratory syncytial virus (RSV),
SARS-CoV-2 (COVID-19) and hepatitis B virus (HBV). 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 with respect to EDP-938 for RSV. 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
development risks of early stage discovery efforts in the disease
areas in Enanta’s research and development pipeline, such as RSV;
the impact of development, regulatory and marketing efforts of
others with respect to competitive treatments for RSV; 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 fiscal quarter ended March 31, 2022 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. Centers for Disease Control & Prevention – Respiratory
Syncytial Virus 2. Centers for Disease Control & Prevention –
RSV in Infants and Young Children 3. Shi, Ting et al. “Global,
regional, and national disease burden estimates of acute lower
respiratory infections due to respiratory syncytial virus in young
children in 2015: a systematic review and modelling study.” Lancet
(London, England) vol. 390,10098 (2017): 946-958.
doi:10.1016/S0140-6736(17)30938-8 4. Falsey, Ann R et al.
“Respiratory syncytial virus infection in elderly and high-risk
adults.” The New England Journal of Medicine vol. 352,17 (2005):
1749-59. doi:10.1056/NEJMoa043951
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version on businesswire.com: https://www.businesswire.com/news/home/20220518006026/en/
Media and Investor Contact Jennifer Viera 617-744-3848
jviera@enanta.com
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