15 March 2016

Positive results from RPL554 dose-finding study

VERONA PHARMA PLC - Positive results from RPL554 dose-finding study

PR Newswire

Verona Pharma plc

("Verona Pharma" or the "Company")

Verona Pharma reports positive results from RPL554 dose-finding study

Study demonstrates drug has substantial bronchodilator effect and excellent tolerability at broad range of doses

Data continues to suggest drug could be meaningful new addition, alone or in combination, for the treatment of COPD

15 March 2016, Cardiff – Verona Pharma plc (AIM: VRP.L), the drug development company focused on first-in-class medicines to treat respiratory diseases, today announces positive headline data from a Phase IIa dose-finding clinical study using the Company’s new proprietary nebulised formulation of RPL554. RPL554 is a novel inhaled PDE3/PDE4 inhibitor with both bronchodilator and anti-inflammatory properties in the same molecule, currently in development as a nebulised treatment for acute exacerbations in chronic obstructive pulmonary disorder (COPD) patients in a hospital or home-care setting. Such patients typically require additional bronchodilation as well as anti-inflammatory treatment despite being on maximum doses of approved COPD medications (which often contain salbutamol).


  • Primary objective of study met

    • Nebulised RPL554 demonstrated a dose-dependent bronchodilator response in asthma patients; the response was highly statistically significant (p<0.0001) at all doses tested1

  • The maximum bronchodilator effect of RPL554 in this study was comparable to the effect observed with the supramaximal dose (7.5mg) of nebulised salbutamol used in this study2

  • RPL554 did not elicit any serious adverse events or adverse events of concern at any dose

    • Large dose range (0.4 to 24mg) examined; suggests RPL554 potentially has a very large safety margin

    • Fewer adverse events recorded with RPL554 than with nebulised salbutamol

    • No gastro-intestinal adverse events or cardiovascular events of concern

  • We continue to expect a Phase II clinical study examining nebulised RPL554 as an add-on treatment to standard bronchodilators to report top-line data in Q2 2016

Dr Jan-Anders Karlsson, the CEO of Verona Pharma, said:

“We are very excited by the results from our dose-finding study for RPL554. It is very pleasing that the maximum bronchodilator effect of RPL554 is comparable to that seen with the highest dose of salbutamol used in the study - a dose equivalent to the highest dose of salbutamol used to treat acute exacerbations of COPD in the emergency department - it is noteworthy that this was achieved with fewer adverse events. The data generated in this study emphasises its pronounced bronchodilator effect, and combined with its unique anti-inflammatory effects, we continue to believe that RPL554 could be an important, and much needed, new treatment option, either alone or as an add-on to existing drugs, for patients with COPD.”

Professor Leif Bjermer of Skane University, Lund, Sweden, lead investigator on this study, commented:

This well-designed and successfully executed dose-ranging study of nebulised RPL554 in moderate asthmatics demonstrated the drug has a linear and thus predictable pharmacokinetic profile, and produced similar bronchodilation but with less side effects compared to a very high dose of salbutamol, used as a comparator. The drug was well tolerated, and few adverse events were recorded. Together, this suggests that the drug could have a large therapeutic index. With further clinical testing, RPL554 could become an important, and much needed novel treatment option, for patients with COPD and other airway’s disease.”

The intent of the study was to demonstrate a dose-dependent bronchodilator effect of RPL554 and compare to nebulised salbutamol. In the hospital setting, the usual starting nebulised dose of salbutamol is 2.5mg but occasionally up to 3 times this dose (7.5mg) is used to produce additional bronchodilation in severely ill patients. We compared RPL554 to both the standard dose and the very high dose of salbutamol to evaluate maximum bronchodilator effects and tolerability.

In this randomised, double-blind, placebo-controlled, seven way crossover Phase IIa study, 29 patients with mild to moderate persistent asthma each received four doses of nebulised RPL554 (0.4 to 24 mg), as well as two doses of nebulised salbutamol (2.5mg and 7.5mg), or placebo. In addition to the largest dose tested in previous studies (24mg), lower doses of the new proprietary nebulised formulation of RPL554 than had been used before, were explored to identify a minimally effective dose. The study was performed at Celerion (Belfast, Ireland) and Skane University Hospital (Lund, Sweden).

The study met its primary objective, with nebulised RPL554 demonstrating a dose-dependent bronchodilator response in asthma patients. RPL554 pharmacokinetics were linear across the whole dose range. At the highest doses of both compounds, RPL554 produced the same maximum bronchodilator effect as salbutamol. Even the lowest RPL554 dose of 0.4mg was significantly superior (p<0.0001) to placebo as a bronchodilator. All doses of RPL554 were found to be well tolerated and the data supports the use of RPL554 in a twice daily dosing regimen. There were no reports of serious adverse events and fewer adverse events were seen with RPL554 than with salbutamol. Salbutamol produced well-acknowledged adverse events for this drug including tremor, tachycardia, palpitations, and a reduction in blood potassium levels. The large dosing range (60 fold) of RPL554 suggests a potentially large therapeutic index.

RPL554 is currently in development as a nebulised treatment for acute exacerbations in COPD patients in a hospital or home-care setting. The data from the study reported today will help inform dose selection in the Phase IIb trial, which it is currently expected to commence in early 2017. 

The nebuliser bronchodilator market was worth about $1 billion in 2014 in the US.3 RPL554 has potential as a novel drug for the maintenance therapy of COPD, and for patients with asthma and cystic fibrosis.


1 The study was carried out in asthmatics as typically a dose response relationship to bronchodilators can be more accurately established in this group of patients, compared to COPD patients

2 Salbutamol is probably the most effective and widely used bronchodilator in asthma and COPD patients. The typical nebulised salbutamol dose range is 2.5mg and sometimes 5mg. A 7.5mg dose of nebulised salbutamol is sometimes used to treat acute exacerbations of COPD or asthma in the emergency department = a supramaximal dose

3 IMS Consulting Group market research 2014


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 Lung and Allergy, Clinical Trial Unit (CTU), Skane University Hospital, Lund, Sweden

The Lung and Allergy clinical trial unit at Skane (http://www.akcsyd.se/forskning/provningsenheten) has been working mainly with early phase II and III studies in Asthma and or COPD for 10 years. The CTU is a part of an academic respiratory research network group run by Professor Leif Bjermer, a recognised expert in this field. The scientific work is focused on disease mechanisms in asthma and COPD, identifying and validating potential new treatment targets by means of invasive and non-invasive techniques, advanced histology, cell and molecular biology. The CTU is equipped with a complete respiratory physiology lab with a special focus on techniques that can address small airway pathology. Biomarkers, biogenetics and functional imaging is also part of the explorative profile. Invasive studies with bronchoscopy, biopsies, brushing and lavage are also performed.

About Celerion Belfast- Center of Excellence for Respiratory (www.celerion.com)

Celerion is a member of the UK’s Translational Research Partnership in Respiratory which is a unique cooperative of internationally leading clinicians and scientists whose aim is to improve the speed of developing innovative therapies for respiratory diseases by working in collaboration with research groups of the pharmaceutical industry. They have been recognized for their excellence in basic and translational research in respiratory medicine.

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 U.S. 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 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.  Carriers have one working copy. People with CF have no working copy. CF therefore has autosomal recessive inheritance. 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 thick, viscous secretions.  Individuals with CF can be diagnosed before birth by genetic testing or by a sweat test in early childhood.  The name cystic fibrosis refers to the characteristic scarring (fibrosis) and cyst formation within the pancreas, first recognised in the 1930s.

Draft Articles of Association 8 Feb 17130.65kb

For further information please contact:


Verona Pharma plc
Jan-Anders Karlsson, CEO
Victoria Stewart, Director of Communications
Tel: +44 (0)20 3283 4200

N+1 Singer (Nominated Adviser and UK Broker)
Aubrey Powell /Jen Boorer /Iqra Amin (Corporate Finance)
Brough Ransom /Mia Gardner (Corporate Broking)
Tel: +44 (0)20 3283 4200



Optimum Strategic Communications
(European Media and Investor enquiries)
Mary Clark, Annemarieke Ezendam
Hollie Vile
Tel: +44 (0) 203 950 9144

Argot Partners (Investor enquiries)
Stephanie Marks
Tel. +1 646 644 9590


Verona Pharma plc
3 More London Riverside, London SE1 2RE
T: +44 (0)203 283 4200

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