VRP Verona Pharma Plc

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

    • 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

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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.