Verona Pharma Announces Publication Of Key Paper On Rpl554 In Copd In The European Respiratory Journal
September 06 2018 - 2:00AM
UK Regulatory
TIDMVRP
Publication demonstrates RPL554's significant bronchodilation effect, in
both large and small airways, alone and when combined with currently
used bronchodilators in COPD patients
LONDON, Sept. 06, 2018 (GLOBE NEWSWIRE) -- Verona Pharma plc (AIM: VRP)
(Nasdaq: VRNA) ("Verona Pharma" or the "Company"), a clinical-stage
biopharmaceutical company focused on developing and commercializing
innovative therapies for respiratory diseases, today announced that the
high-impact, peer reviewed European Respiratory Journal has published a
paper entitled "The short term bronchodilator effects of the dual PDE3
and PDE4 inhibitor RPL554 in COPD" that provides full results from two
positive Phase 2 clinical studies with RPL554.(*) Results from these
studies were previously reported by Verona Pharma on May 10, 2016 and
September 7, 2017. RPL554 is the Company's lead first-in-class drug
candidate that has a dual bronchodilator and anti-inflammatory mechanism
of action. RPL554 has potential as an add-on therapy to improve lung
function and reduce symptom severity in chronic obstructive pulmonary
disease (COPD) patients whose disease is not being adequately managed by
the current standard of care.
Highlights
Publication details results from two studies demonstrating that RPL554
combined with standard short- and long-acting bronchodilators:
-- Causes a pronounced additional bronchodilator effect in both large and
small airways.
-- Reduces lung hyperinflation, considered a cause of breathlessness in COPD
patients.
-- Improves speed of onset of action when combined with standard
bronchodilators.
The first study detailed in the publication compared the short-term
bronchodilator effects of nebulized RPL554 with that of the commonly
used bronchodilators salbutamol (a short-acting beta-agonist) and
ipratropium (a short-acting anti-muscarinic agent), as well as placebo,
in patients with reversible COPD. Additional bronchodilator effects
when adding RPL554 on top of these agents was also measured.
The second study detailed the extent of any additional bronchodilation
that is achievable, in this patient group, when adding RPL554 to
tiotropium (the long-acting anti-muscarinic Spiriva(R) , one of the most
commonly used drugs to treat COPD). In both studies, peak forced
expiratory volume in one second (FEV(1) ) lung volumes and specific
airway conductance (sGAW) were studied as the principle measures of
airway function. In both studies RPL554 demonstrated a placebo like
side-effect profile.
The statistically significant results from these studies clearly
demonstrate that the bronchodilator effect of RPL554 in patients with
reversible COPD is, at the very least, of similar magnitude as that of
the commonly used bronchodilators studied, and that clinically
meaningful additional bronchodilation could be achieved by adding RPL554
to the treatment of patients with such drugs. The paper concludes that
"...RPL554 provided additional bronchodilation, reduced gas trapping,
improved airway conductance, and a more rapid onset of action when
administered in combination with either a beta-2 agonist or muscarinic
antagonist. These short-term bronchodilator studies provide support to
further study RPL554 in longer term COPD studies focused on other
endpoints including symptoms and exacerbations."
Jan-Anders Karlsson, PhD, CEO of Verona Pharma, said: "The statistically
significant results from the two Phase 2 trials detailed in this
important paper continue to highlight the potential and differentiated
profile of RPL554 as an add-on therapy to improve lung function and
reduce symptom severity in COPD patients whose disease is not being
adequately managed by the current standard of care."
Dave Singh, M.D., Professor of Clinical Pharmacology and Respiratory
Medicine, Medicines Evaluation Unit, University of Manchester, and
Principal Investigator in these studies, added: "The results published
in the European Respiratory Journal not only profile the significant
effect of RPL554 on improving lung function in COPD patients when used
alone or in combination with commonly used bronchodilators, but also its
rapid onset of action, especially when used in combination."
Verona Pharma is currently conducting a Phase 2 clinical trial to
evaluate RPL554 as an add-on treatment to dual LAMA/LABA therapy and
triple LAMA/LABA/ICS therapy, as part of a comprehensive clinical
program to fully demonstrate the clinical utility of RPL554 in improving
the standard of care for COPD. These data will also support the planning
of the RPL554 phase 3 program.
Paper Abstract in Full
Introduction: We investigated the short-term bronchodilator effects of
RPL554 (an inhaled dual phosphodiesterase 3 and 4 inhibitor) combined
with other bronchodilators in COPD patients with reversibility (>150 mL
to short acting bronchodilators).
Methods: Study 1: six way placebo controlled crossover study (n=36) with
single doses of RPL554 (6mg), salbutamol (200<MU>g), ipratropium
(40<MU>g), RPL554 + salbutamol, RPL554 + ipratropium and placebo. Study
2: three way crossover study (n=30) of tiotropium (18 <MU>g) combined
with RPL554 (1.5 mg or 6mg) or placebo for 3 days. FEV(1) , lung volumes
and sGaw were measured.
Results: Study 1; Peak FEV(1) change compared to placebo was similar
with RPL554, ipratropium and salbutamol (means 223, 199 and 187 mL
respectively). The peak FEV(1) was higher for RPL554 + ipratropium
versus ipratropium (mean difference 94 mL, p<0.0001) and RPL554 +
salbutamol versus salbutamol (mean difference 108 mL; p<0.0001). Study 2
(day 3); both RPL554 doses caused greater peak FEV(1) effects than
placebo. The average FEV(1) (0- 12h) increase was greater with RPL554
6mg only versus placebo (mean difference 65 mL p=0.0009). In both
studies, lung volumes and sGAW showed greater RPL554 combination
treatment effects versus monotherapy.
Conclusion: RPL554 combined with standard bronchodilators caused
additional bronchodilation and hyperinflation reduction.
About COPD
Chronic obstructive pulmonary disease ("COPD") is a progressive and
life-threatening respiratory disease for which there is no cure.(1)
Although COPD is thought to be underdiagnosed, globally, around 384
million people suffer from the disease.(2) This number, according to the
World Health Organization ("WHO"), is likely to increase in coming years,
with estimates that COPD will become the third leading cause of death
worldwide by 2030.(1,3) 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.(1) 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.(4) 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.(5) 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.(6) There is an urgent need for drugs with novel
mechanisms of action that can be used by these patients in addition to
current therapies.
_______________
(*) Singh D et al; Eur Respir J. 2018 Aug 30. pii: 1801074.
https://doi.org/10.1183/13993003.01074-2018
About Verona Pharma plc and RPL554
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, RPL554, is a first-in-class, inhaled, dual
inhibitor of the enzymes phosphodiesterase 3 and 4 that acts as both a
bronchodilator and an anti-inflammatory agent in a single compound. In
previous clinical trials, RPL554 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. RPL554 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,
RPL554 has shown anti-inflammatory effects in a standard challenge study
with COPD-like inflammation in human subjects. RPL554 has been well
tolerated in these studies and has a favorable safety and tolerability
profile, having been administered to more than 730 subjects in 12
clinical trials. Verona Pharma is developing RPL554 for the treatment of
chronic obstructive pulmonary disease ("COPD"), cystic fibrosis ("CF"),
and potentially 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 regarding the design of the
Phase 2 clinical trial of RPL554, the timing of availability of top-line
data for the Phase 2 clinical trial, the importance of the Phase 2
clinical trial to our development plans for RPL554, the potential of
RPL554 as a promising first-in-class treatment option for COPD, and the
value of the data and insights that may be gathered from the Phase 2
clinical trial, including for the purpose of designing pivotal Phase 3
trials.
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 and the
completion of our Phase 2 trial; we may not be successful in developing
RPL554 for multiple indications; our ability to obtain regulatory
approvals necessary to conduct later stage trials and to 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 relating to our
Registration Statement on Form F-1, 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)
James Heins Tel: +1 203-682-8251
James.Heins@icrinc.com
Stephanie Carrington Tel. +1 646-277-1282
Stephanie.Carrington@icrinc.com
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