Verona Pharma plc Verona Pharma Reports Encouraging Top-Line Data From Three-Day Phase 2 Trial Evaluating Nebulized Ensifentr...
14 January 2019 - 6:00PM
UK Regulatory
TIDMVRP
Results from this short clinical pharmacology trial inform and support
further clinical development of ensifentrine as an add-on to dual and
triple COPD therapy
Investment community conference call scheduled for 8 am EST on Monday,
January 14, 2019
LONDON, Jan. 14, 2019 (GLOBE NEWSWIRE) -- Verona Pharma plc (AIM:VRP)
(Nasdaq:VRNA) ("Verona Pharma"), a clinical-stage biopharmaceutical
company focused on developing and commercializing innovative therapies
for respiratory diseases, announces top-line data from its three-day
Phase 2 clinical pharmacology trial evaluating the effect of two
different doses (1.5 mg and 6.0 mg; twice daily) of nebulized
ensifentrine (RPL554) when used on top of an inhaled long-acting
muscarinic antagonist/long-acting beta2 agonist ("LAMA/LABA"),
tiotropium/olodaterol (Stiolto(R) Respimat(R) ). LAMA/LABA therapies are
commonly used in the maintenance treatment of patients with moderate to
severe chronic obstructive pulmonary disease ("COPD"). Patients already
receiving inhaled corticosteroid ("ICS") therapy were allowed to
continue to receive a stable dose of ICS throughout the study, thus
providing additional data on "triple therapy" use.
Ensifentrine is an investigational first-in-class, inhaled, dual
inhibitor of the enzymes phosphodiesterase 3 and 4 designed to have
bronchodilator and anti-inflammatory properties, which is currently in
development for the maintenance treatment of COPD, cystic fibrosis and
asthma.
Highlights
-- Primary endpoint of peak forced expiratory volume in one second ("FEV1")
after morning dose on day 3 of treatment was not met with statistical
significance, although the ensifentrine 1.5 mg morning dose improved peak
FEV1 by 46 mL, compared to placebo.- Improvement in FEV1, compared to
placebo, with the 1.5 mg dose was maintained throughout the 24-hour
period as measured on day 3.
-- Importantly, peak FEV1 after evening dose on day 3 showed statistically
significant improvement, compared to placebo, with both doses, with
ensifentrine 1.5 mg showing a 130 mL improvement (p<0.001) and
ensifentrine 6.0 mg showing an 81 mL improvement (p=0.002).
-- Ensifentrine at a 1.5 mg dose produced consistent improvements, compared
to placebo, in average FEV1 over 12 hours following the morning dose on
days 1 to 3, with an improvement of approximately 50 mL on day 3. These
improvements were not shown to be statistically significant when adjusted
for multiple doses.
-- Reductions in residual volume, compared to placebo, as measured by
plethysmography were observed at all time points on day 3 with the 1.5 mg
dose.- Statistically significant reductions in mean residual volume were
observed 15 minutes following the evening dose on day 3, with
ensifentrine 1.5 mg showing a reduction of 259 mL (p<0.002) and
ensifentrine 6.0 mg showing a reduction of 142 mL (p<0.036).
-- Ensifentrine 6.0 mg did not result in greater improvement in lung
function as compared with the ensifentrine 1.5 mg dose.
-- Ensifentrine was well tolerated at both doses with an adverse event
profile consistent with that observed in prior studies.
"Achieving additional bronchodilator response of this magnitude in COPD
patients that have previously been considered to be maximally
bronchodilated on background dual or triple therapy in a short,
three-day study is clinically meaningful and unprecedented," commented
Dave Singh, M.D., Professor of Clinical Pharmacology and Respiratory
Medicine, Medicines Evaluation Unit, University of Manchester. "The
statistically significant reduction observed in residual volume for the
ensifentrine 1.5 mg dose at certain time points, which is closely
related to dyspnea or breathlessness, highlights the potential for
ensifentrine to provide symptomatic improvement for patients with this
progressive and debilitating disease. I look forward to seeing data from
longer-term studies evaluating the bronchodilator and anti-inflammatory
activity of this unique mechanism of action."
"Having demonstrated in previous studies the potential of ensifentrine
to deliver benefits to patients on no or single bronchodilator therapy,
we believe that this short study continues to support our view that
ensifentrine may also be of benefit to more severe COPD patients on dual
and triple therapy, for whom there are few other treatment options,"
said Jan-Anders Karlsson, PhD, CEO of Verona Pharma. "While we are
disappointed that this exploratory Phase 2 study did not achieve
statistical significance for its primary endpoint, these data give us
clarity on the design, including dose and background therapy, for future
long-term studies. We now have the opportunity to also include patients
on dual and triple therapy, with the goal of further evaluating
ensifentrine's potential to produce sustained bronchodilation and
anti-inflammatory effect in this large number of symptomatic COPD
patients."
In Phase 2 clinical trials completed to date, ensifentrine has been
observed to result in bronchodilator effects when used alone or as an
add-on treatment to other COPD bronchodilators, and has also shown
anti-inflammatory effects in a standard challenge study with COPD-like
inflammation in human subjects. Verona Pharma is currently conducting a
Phase 2 trial to evaluate a dry powder inhaler formulation of
ensifentrine for the maintenance treatment of COPD. The company also
plans to evaluate ensifentrine in a metered-dose inhaler formulation as
part of a comprehensive clinical program intended to fully demonstrate
the clinical utility of ensifentrine in improving the standard of care
for COPD.
Study Design
This study was a randomized, double-blind, three-way crossover trial
(ClinicalTrials.gov Identifier: NCT0367367), conducted at sites in the
U.S. and in the U.K., which enrolled 79 patients with COPD to
investigate the efficacy and safety of nebulized ensifentrine (RPL554)
on top of an inhaled LAMA/LABA, tiotropium/olodaterol (Stiolto(R)
Respimat(R) ), compared to placebo. Approximately 40% of patients were
already receiving ICS anti-inflammatory therapy before the study and
were allowed to continue to receive a stable dose of ICS throughout the
study, thus providing additional data on "triple therapy" use. Following
a 7- to 14-day washout period in advance of dosing and between study
arms, patients received three days of treatment with each of two dose
strengths (1.5 mg or 6.0 mg) of nebulized ensifentrine or placebo twice
daily. The primary endpoint of this trial was improvement in lung
function with ensifentrine (as an add-on to tiotropium/olodaterol),
compared to placebo, as measured by FEV(1) , a standard measure of
exhaled breath volume to evaluate respiratory function, four hours
post-dose after the morning dose on day three. Secondary endpoints
included lung function as measured by FEV(1) over time, reductions in
residual volume, and safety and tolerability.
Conference Call
Verona Pharma will host an investment community conference call today at
8:00 a.m. Eastern Standard Time (1:00 p.m. Greenwich Mean Time) on
Monday, January 14, 2019 to discuss the top-line data from the study
disclosed in this press release.
Analysts and investors may participate in the conference call by
utilizing the conference ID: 13686524 and dialing the following numbers:
-- 1-877-423-9813 or + 1-201-689-8573 for callers in the United States
-- 0 800 756 3429 for callers in the United Kingdom
-- 0 800 182 0040 for callers in Germany
Those interested in listening to the conference call live via the
internet may do so by visiting the "Events and Presentations" page on
the "Investors" section of Verona Pharma's website at
https://www.globenewswire.com/Tracker?data=9gFx8HTqyeMmTmyhq7yep-hPJjrjrJ3UIUyehYupbMnoKaicue-7w1b0fWA2C4Tt0xIhIa5dzif4UKHuY16SPeCvcMf-AlC-G7NOJxquaaimuXlusbaGwa3ldpuD73jPSFVlZxtmHJpOmnHLFM980B9gRtnvcpMJ1uT6VbYd5n8Fy2EuXgti3PdQr6FZ-3362YAkZ8Tyg8T6ZvMd04CRpNA056AKoKtBTaCQcoam_jX2xgl77qQixU_MOd_hy1pvQvpa3OJbEIftnlZAqjWPk50uN4aHzsRUEHz0qwUC_pFpZQK6EcMni7GBCen7_bHLX8ZGbKgUeePteFdJRrpOvhBIKFSk6n-4IFFdw9sjx5hAvoRLC1F_kzLhfY_DlHKGrVjX0qVVS2jA2CwJoTdEoXxCNRk2THOH41uzu1kl6Zu8dhd4bqfvYhbui5skp6PtbRAHUrIqNsOuOtRRbgvulw==
http://investors.veronapharma.com/events-and-presentations/events and
clicking on the webcast link. Slides highlighting the top-line data will
also be posted to the "Events and Presentations" page.
THIS ANNOUNCEMENT CONTAINS INSIDE INFORMATION FOR THE PURPOSES OF
ARTICLE 7 OF REGULATION (EU) NO 596/2014.
About Chronic Obstructive Pulmonary Disease
Chronic obstructive pulmonary disease ("COPD") is a progressive and
life-threatening respiratory disease for which there is no cure.
Although COPD is thought to be underdiagnosed, globally, around 384
million people suffer from the disease. This number, according to the
World Health Organization, is likely to increase in coming years, with
estimates that COPD will become the third leading cause of death
worldwide by 2030. The condition damages the airways and the lungs,
leading to persistent symptoms of breathlessness, impacting a person's
daily life and their ability to perform simple activities such as
walking a short flight of stairs or carrying a suitcase. Many experience
acute periods of worsening symptoms called 'exacerbations', often
leading to emergency department visits or hospital admissions and are
also associated with high mortality. In the United States alone, the
2010 total annual medical costs related to COPD were estimated to be $32
billion and are projected to rise to $49 billion in 2020. About 30-40%
of moderate to severe COPD patients on triple inhaled therapy
(ICS/LAMA/LABA) remain uncontrolled and continue to experience airway
obstruction (breathing difficulties), COPD symptoms and exacerbations.
There is an urgent need for drugs with novel mechanisms of action that
can be used by these patients in addition to current therapies.
About Verona Pharma plc
Verona Pharma is a clinical-stage biopharmaceutical company focused on
developing and commercializing innovative therapies for the treatment of
respiratory diseases with significant unmet medical needs. Verona
Pharma's product candidate, ensifentrine, is an investigational
first-in-class, inhaled, dual inhibitor of the enzymes phosphodiesterase
3 and 4 that is designed to act as both a bronchodilator and an
anti-inflammatory agent in a single compound. In previous clinical
trials, the nebulized formulation of ensifentrine has been observed to
result in bronchodilator effects when used alone or as an add-on
treatment to other COPD bronchodilators. It has shown clinically
meaningful and statistically significant improvements in lung function
when administered in addition to frequently used short- and long-acting
bronchodilators, such as tiotropium (Spiriva(R) ), compared with such
bronchodilators administered as a single agent. Ensifentrine improved
FEV(1) over four weeks in patients with moderate-to-severe COPD when
compared to placebo and improved COPD symptoms and quality of life in a
Phase 2b multicenter European study performed in 403 patients. In
addition, ensifentrine has shown anti-inflammatory effects in a standard
challenge study with COPD-like inflammation in human subjects.
Ensifentrine has been well tolerated in these studies, having been
administered to more than 800 subjects in 13 clinical trials. Verona
Pharma is developing ensifentrine for the treatment of COPD, CF, and
asthma.
Forward-Looking Statements
This press release contains forward-looking statements. All statements
contained in this press release that do not relate to matters of
historical fact should be considered forward-looking statements,
including, but not limited to, statements that there is an opportunity
for additional bronchodilator and symptomatic improvement via the novel
mechanism of action of ensifentrine and Verona Pharma's plans to carry
out further long-term clinical studies of ensifentrine as an add-on to
both single and dual bronchodilator therapy and the expectation that
even more profound anti-inflammatory effects, leading to improvements in
lung function, as well as improvements in symptoms will result.
These forward-looking statements are based on management's current
expectations. These statements are neither promises nor guarantees, but
involve known and unknown risks, uncertainties and other important
factors that may cause our actual results, performance or achievements
to be materially different from our expectations expressed or implied by
the forward-looking statements, including, but not limited to, the
following: our limited operating history; our need for additional
funding to complete development and commercialization of RPL554, which
may not be available and which may force us to delay, reduce or
eliminate our development or commercialization efforts; the reliance of
our business on the success of RPL554, our only product candidate under
development; economic, political, regulatory and other risks involved
with international operations; the lengthy and expensive process of
clinical drug development, which has an uncertain outcome; serious
adverse, undesirable or unacceptable side effects associated with
RPL554, which could adversely affect our ability to develop or
commercialize RPL554; potential delays in enrolling patients, which
could adversely affect our research and development efforts; we may not
be successful in developing RPL554 for multiple indications; our ability
to obtain approval for and commercialize RPL554 in multiple major
pharmaceutical markets; misconduct or other improper activities by our
employees, consultants, principal investigators, and third-party service
providers; material differences between our "top-line" data and final
data; our reliance on third parties, including clinical investigators,
manufacturers and suppliers, and the risks related to these parties'
ability to successfully develop and commercialize RPL554; and lawsuits
related to patents covering RPL554 and the potential for our patents to
be found invalid or unenforceable. These and other important factors
under the caption "Risk Factors" in our Annual Report on Form 20-F filed
with the Securities and Exchange Commission ("SEC") on February 27,
2018, and our other reports filed with the SEC, could cause actual
results to differ materially from those indicated by the forward-looking
statements made in this press release. Any such forward-looking
statements represent management's estimates as of the date of this press
release. While we may elect to update such forward-looking statements at
some point in the future, we disclaim any obligation to do so, even if
subsequent events cause our views to change. These forward-looking
statements should not be relied upon as representing our views as of any
date subsequent to the date of this press release.
For further information, please contact:
Verona Pharma plc Tel: +44 (0)20 3283 4200
Jan-Anders Karlsson, Chief Executive Officer info@veronapharma.com
Stifel Nicolaus Europe Limited (Nominated Adviser Tel: +44 (0) 20 7710 7600
and UK Broker)
Stewart Wallace / Jonathan Senior / Ben Maddison
FTI Consulting (UK Media and Investor enquiries) Tel: +44 (0)20 3727 1000
Simon Conway / Natalie Garland-Collins veronapharma@fticonsulting.com
ICR, Inc. (US Media and Investor enquiries)
Darcie Robinson Tel: +1 203-919-7905
Darcie.Robinson@icrinc.com
Stephanie Carrington Tel. +1 646-277-1282
Stephanie.Carrington@icrinc.com
(END) Dow Jones Newswires
January 14, 2019 02:00 ET (07:00 GMT)
Copyright (c) 2019 Dow Jones & Company, Inc.
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