Verona Pharma PLC Add-on Phase II RPL554 study

 
TIDMVRP 
 
Verona Pharma plc 
 
                      ("Verona Pharma" or the "Company") 
 
  Verona Pharma announces positive results from "add-on" Phase II trial with 
                                    RPL554 
 
RPL554 produced over 60% additional bronchodilation on top of standard of care 
                       bronchodilators in COPD patients 
 
 Data implies RPL554, alone or in combination with other bronchodilators, may 
             reduce dyspnea, a major debilitating symptom of COPD 
 
10 May 2016, Cardiff - Verona Pharma plc (AIM: VRP.L), the drug development 
company focused on first-in-class medicines to treat respiratory diseases, 
today announces highly positive headline data from a Phase IIa study that 
assessed the bronchodilator effect of nebulised RPL554 administered on top of 
salbutamol and ipratropium bromide in patients with COPD. RPL554 is a novel 
inhaled dual PDE3/PDE4 inhibitor with both bronchodilator and anti-inflammatory 
properties in the same molecule, which is currently in development as a 
nebulised treatment for acute exacerbations in chronic obstructive pulmonary 
disorder (COPD) patients in a hospital or for maintenance treatment in a 
home-care setting. Such patients typically require additional bronchodilation, 
despite being on approved COPD bronchodilator medications such as salbutamol, a 
beta2-agonist, and ipratropium bromide, an anti-muscarinic. 
 
Highlights 
 
  * Primary objective of study met 
 
      + RPL554 produced a highly significant (p?0.001) and a clinically 
        meaningful additional (>60%) bronchodilation on top of the administered 
        standard of care bronchodilators, salbutamol and ipratropium bromide 
 
      + The bronchodilator effects seen with the combinations were 
        significantly (p?0.001) larger than those of either salbutamol or 
        ipratropium bromide alone, which were in turn all significantly greater 
        than placebo 
 
  * Secondary objectives also met including 
 
      + The combination of RPL554 with salbutamol or ipratropium bromide caused 
        a significant reduction (p=0.0002 and p=0.004 respectively) in trapped 
        air in the lung (residual volume) as compared to salbutamol or 
        ipratropium bromide alone 
 
          o Suggesting that RPL554 treatment may reduce dyspnea, a major 
            debilitating symptom of COPD1 
 
  * Consistent with previous studies, RPL554 was well tolerated both alone and 
    in combination 
 
      + No effect on vital signs or ECG parameters 
 
      + No gastro-intestinal adverse events recorded 
 
Professor Dave Singh of the Medicines Evaluation Unit, University of Manchester 
and Principal Investigator in this trial, commented: 
 
"Achieving more than an additional 60% improvement in lung function on 
administration of RPL554 in moderate to severe COPD patients, already 
pre-treated with standard of care bronchodilators, is clinically highly 
significant, especially as the addition of RPL554 appears to be well 
tolerated." 
 
Dr Jan-Anders Karlsson, the CEO of Verona Pharma, said: 
 
"The robustly positive results from this well-controlled Phase IIa trial 
vindicate the rationale for developing a novel bronchodilator for treatment of 
patients with moderate to severe disease and acute exacerbations of COPD, who 
will typically already be on other bronchodilators, but require additional 
relief." 
 
"With the successful conclusion of this trial, we now believe we have the 
required data in hand from our Phase IIa studies to progress RPL554 confidently 
into a Phase IIb clinical trial programme. This will explore further its 
potential as a novel nebulised treatment for moderate to severe COPD patients 
in a hospital or home-care setting, a multi-billion dollar market." 
 
The nebuliser bronchodilator market was worth about $1 billion in 2014 in the 
US.2 RPL554 also has potential as a novel drug for the maintenance therapy of 
COPD, and for patients with asthma and cystic fibrosis. 
 
Details of the clinical study 
 
In this Phase II randomised, double blind, placebo controlled, six-way 
crossover study patients with moderate to severe COPD were randomised to 
receive a single dose from a blinded pressured metered dose inhaler (pMDI), 
containing either salbutamol (200 micrograms) or placebo followed by a single 
dose from a second blinded pMDI which contained ipratropium bromide (40 
micrograms) or placebo. This was followed immediately by a single double blind 
dose of nebulised RPL554 (6mg) or placebo. Lung function was measured pre-dose 
and up to 12h post dose. The administered salbutamol and ipratropium bromide 
doses used in this study are standard approved doses of these medications for 
COPD patients. 30 subjects completed the study. 
 
The study met its primary objective of a statistically significant increase in 
peak forced expiratory volume in one second, FEV1, (p<0.001) and a 
statistically significant increase in average FEV1 response over 8 hours (p 
<0.001). All treatments including RPL554 when given as single agents were 
significantly (p<0.001) better than placebo.  RPL554 added over 60% additional 
bronchodilation on top of either salbutamol or ipratropium bromide. 
 
Secondary outcome measures were change in lung volumes and airway conductance 
as well as safety.  There was a marked, statistically significant reduction in 
trapped air in the lung (residual volume) indicating an improvement in lung 
hyperinflation. As with FEV1, the combination of RPL554 and either salbutamol 
or ipratropium was more effective than either agent alone.  This should 
translate into an improvement in dyspnea (shortness of breath), a major 
debilitating symptom of COPD, and suggests that RPL554 is having an effect both 
in central and peripheral airways. RPL554 was well tolerated both alone and in 
combination with the other bronchodilators used in the study. There was no 
effect of RPL554 alone or in combination on vital signs or ECG parameters 
 
The study was conducted at The Medicines Evaluation Unit ("MEU"), one of the 
UK's leading contract research organisations under principal investigator 
Professor Dave Singh. 
 
The data from the study reported today will help inform the trial design for 
the forthcoming Phase IIb study, which it is currently expected to commence in 
early 2017. 
 
1 Dyspnea (shortness of breath) in COPD patients is often associated with 
hyperinflation of the lungs resulting from a higher residual volume of air 
 
2 IMS Consulting Group market research 2014 
 
                                    -Ends- 
 
For further information, please contact: 
 
Verona Pharma plc                      Tel: +44 (0)20 7863 3300 
 
Jan-Anders Karlsson, CEO 
 
N+1 Singer                             Tel: +44 (0)20 7496 3000 
 
Aubrey Powell / Jen Boorer 
 
FTI Consulting                         Tel: +44 (0)20 3727 1000 
 
Simon Conway / Julia Phillips 
 
Notes to Editors 
 
About Verona Pharma plc 
 
Verona Pharma plc is a UK-based clinical stage biopharmaceutical company 
focused on the development of innovative prescription medicines to treat 
respiratory diseases with significant unmet medical needs, such as chronic 
obstructive pulmonary disease (COPD), asthma and cystic fibrosis. 
 
Verona Pharma's lead drug, RPL554, is a first-in-class drug currently in Phase 
2 trials as a nebulised treatment for acute exacerbations of COPD in the 
hospital setting. The drug is a dual phosphodiesterase (PDE) 3/4 inhibitor and 
therefore has both bronchodilator and anti-inflammatory effects, which are 
essential to the improvement of patients with COPD and asthma. 
 
Verona Pharma is also building a broader portfolio of RPL554-containing 
products to maximise its benefit to patients and its value.  This includes the 
very significant markets for COPD and asthma maintenance therapy.  In addition, 
the Company is exploring the potential of the drug in different diseases, such 
as cystic fibrosis, where it is in pre-clinical testing and has received a 
Venture and Innovation Award from the UK Cystic Fibrosis Trust. 
 
About The Medicines Evaluation Unit 
 
The Medicines Evaluation Unit ("MEU") is one of the UK's leading contract 
research organisations, working in collaboration with the University Hospital 
of South Manchester. The MEU specialises in performing clinical trials (from 
Phase I through to IV) in respiratory/inflammatory medicine and related areas. 
The MEU has an outstanding reputation for performing high quality clinical 
research complying with UK Clinical Trials legislation and EU Directives. 
 
About Chronic Obstructive Pulmonary Disease (COPD) 
 
Sixty-five million people worldwide suffer from moderate to severe COPD and the 
World Health Organisation (WHO) expects COPD to be the third leading cause of 
death globally by 2020.  It is the only major chronic disease with increasing 
mortality.  Currently available drugs are aimed at long-term maintenance 
therapy, with the market dominated by large pharma.  Despite the wide 
availability of these therapies, COPD patients suffer acute periods of 
worsening symptoms (exacerbations), which cause, in the US alone, some 1.5 
million A&E visits, 726,000 hospitalisations and 120,000 deaths per annum. 
 
About Asthma 
 
Asthma remains one of the most common chronic diseases in the world and is 
characterised by recurrent breathing problems and symptoms such as 
breathlessness, wheezing, chest tightness, and coughing.  In the US asthma 
accounts for approx. 1.9 million annual emergency room visits and approx. 
500,000 annual hospitalisations. 
 
About Cystic Fibrosis 
 
Cystic fibrosis (CF) is an orphan disease that afflicts approximately 70,000 
people worldwide. The disease affects mostly the lungs, and also the pancreas, 
liver, and intestine. Difficulty in breathing is the most serious symptom and 
results from frequent lung infections. CF is caused by one of many different 
mutations in the gene for the protein cystic fibrosis transmembrane conductance 
regulator (CFTR). This protein is required to regulate the components of sweat,

digestive fluids, and mucus. Healthy people have two working copies of the CFTR 
gene, and people with CF have two faulty copies of the gene The underlying 
mechanism is abnormal transport of chloride and sodium across the epithelium, 
which is the cell layer that covers membranes over organs.  This leads to the 
build-up of thick, viscous secretions.  New-born screening is now offered to 
all babies in the UK to help diagnose CF. 
 
 
 
END

(END) Dow Jones Newswires

May 10, 2016 02:00 ET (06:00 GMT)

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