VRP.L Regulatory News (VRP)

VERONA PHARMA PLC - RPL554 MAD study complete

PR Newswire

London, June 8

Verona Pharma plc

("Verona Pharma" or the "Company")

RPL554 MAD study in healthy volunteers confirms excellent tolerability;dosing of COPD patients commencesMultiple ascending dose study of RPL554 in healthy volunteers completed successfully; excellent tolerability at all dose levels tested

Results continue to support twice daily dosing regimen with new RPL554 formulation

Up to 30 COPD patients to be treated in multiple ascending dose study;results expected Q3 2015

8 June 2015, Cardiff – Verona Pharma plc (AIM: VRP.L), the drug development company focused on first-in-class medicines to treat respiratory diseases, today announces the successful completion of the second phase of a Multiple Ascending Dose (MAD) study in which nebulised RPL554, a novel dual PDE3/PDE4 inhibitor, was administered to healthy subjects for up to five consecutive days at doses up to 16x larger than the previously used active dose. RPL554 is currently in development as a nebulised treatment for acute exacerbations in COPD patients in a hospital or home-care setting. The nebulised bronchodilator market was worth about $1 billion in 2014 in the US1.

The completed MAD study showed that the drug was well tolerated across all dose levels and no maximum tolerated dose was reached. As found in the interim results from the single ascending dose (SAD) part of this trial, repeat dosing with the new formulation resulted in a longer residence time for RPL554 in the lung and slower release into the blood stream, suggesting that twice daily dosing may be appropriate.

The Company also announces the commencement of a multiple ascending dose study in up to 30 moderate chronic obstructive pulmonary disease (COPD) patients, where each dose will be given for five consecutive days. The primary objective here is to further confirm the safety and tolerability seen in earlier parts of the trial, as well as to investigate bronchodilation in these COPD patients. This study is the final part of a Phase I/II clinical trial with RPL554, using a new proprietary nebulised formulation.

The dose range, for both MAD studies, is based on the successfully completed SAD part of this trial in which nebulised RPL554 was delivered at doses up to 16x that previously shown to produce bronchodilation. As noted in Verona Pharma’s press release on 23 March 2015, RPL554, in this study in 50 healthy volunteers, was well-tolerated and was without effect on cardio-vascular parameters and without nausea or vomiting at any dose.

The trial is being performed at the Medicines Evaluation Unit in Manchester by lead investigator Professor Dave Singh.

Dr Jan-Anders Karlsson, Chief Executive Officer of Verona Pharma, said:

“This proof of concept trial with our new proprietary formulation for nebulised RPL554 continues to generate very encouraging results. The drug appears to be very well tolerated on both single and multiple dosing even at significantly elevated levels compared to previous doses tested. The final phase of this trial will be conducted in COPD patients and will examine both the safety and bronchodilator response at higher doses. We have already demonstrated in previous trials at lower doses using an earlier formulation that RPL554 is a potent bronchodilator with broad anti-inflammatory activity in a single molecule. Accordingly we eagerly await the results from the final part of this study, expected in Q3 2015. 

“We are initially developing nebulised RPL554 as a treatment for acute exacerbations in COPD, where we believe it has significant market potential. We continue to believe that the emerging profile of RPL554 suggests that it could potentially become an important addition to available treatment options both as a monotherapy and, as a result of its unique mechanism of action, as a combination partner for existing drugs for COPD.”

Phase I and Phase II studies with RPL554 in its previous nebulised formulation were successfully conducted in over 100 subjects.2 Results collectively showed that the drug is a very potent bronchodilator with the ability to elicit a unique anti-inflammatory response. In these initial studies, patients treated with RPL554 had an adverse event profile which was similar to that in patients treated with placebo. The original nebulised formulation of the drug used in these studies was devised to provide proof-of-concept data, before developing the new formulation suitable for commercial scale-up.

It is expected that the new formulation of RPL554 will result in a significantly improved therapeutic index in COPD patients, implying that they should be able to inhale higher doses with prolonged effect, than the previous prototype formulation, offering potential for improvements in convenience and compliance, as well as health economic benefit. In addition, the commercial viability of the new formulation is underlined by significantly improved stability compared to the previous formulation. RPL554 also has potential as a novel therapy in patients with asthma and cystic fibrosis.

-Ends

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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 II 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. The Company is also exploring the potential of the drug in different diseases, such as cystic fibrosis, where it is in pre-clinical testing and has recently received a Venture and Innovation Award from the 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 and holds MHRA Phase I accreditation.

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 3rd 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.

1 IMS Consulting Group market research 2014

2 Franciosi, L.G., et al., Efficacy and safety of RPL554, a dual PDE3 and PDE4 inhibitor, in healthy volunteers and in patients with asthma or chronic obstructive pulmonary disease: findings from four clinical trials. Lancet Respir Med, 2013. 1(9): p. 714-27.