Verona Pharma plc Verona Pharma Reports Encouraging Top-Line Data From Three-Day Phase 2 Trial Evaluating Nebulized Ensifentr...

 
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: [phone] 
Jan-Anders Karlsson, Chief Executive Officer       [e-mail] 
 
Stifel Nicolaus Europe Limited (Nominated Adviser  Tel: [phone] 
 and UK Broker) 
Stewart Wallace / Jonathan Senior / Ben Maddison 
 
FTI Consulting (UK Media and Investor enquiries)   Tel: [phone] 
Simon Conway / Natalie Garland-Collins             [e-mail] 
 
ICR, Inc. (US Media and Investor enquiries) 
Darcie Robinson                                    Tel: [phone] 
                                                    [e-mail] 
Stephanie Carrington                               Tel. [phone] 
                                                    [e-mail] 
 
 
 
 
 
 

(END) Dow Jones Newswires

January 14, 2019 02:00 ET (07:00 GMT)

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