Staying up-to-date has never been simpler. Sign up for the free GenePool newsletter today!
21 May 2013 -- Verona Pharma plc (AIM: VRP), the drug development company focused on “first-in-class” medicines to treat
respiratory diseases, today announces that a further poster was presented on Tuesday 21 May as part of the
scientific programme at American Thoracic Society (ATS) International Conference, Philadelphia, USA, 17-
22 May 2013. The abstract for this poster is reproduced below.
[Poster Board # 315] RPL554, A Dual PDE3/4 Inhibitor, Is Well Tolerated And Maintains
Bronchodilator Activity When Administered By Inhalation To Mild-To-Moderate Allergic Asthmatics
On 6 Consecutive Days, [Publication Page: A3875]
L. Franciosi, PhD1, R. Zuiker, MD, MBA2, I.M. Kamerling, MD2, J. Burgraaf, MD, PhD2, A. Cohen, MD,
PhD2, M. Walker, PhD1, C. Page, PhD1
Rationale: RPL554, an inhaled dual phosphodiesterase 3/4 inhibitor, has bronchodilator, bronchoprotective
and anti-inflammatory properties in pre-clinical models of allergen-induced asthma. Single doses of
nebulized RPL554 in healthy subjects and allergic asthmatics were well tolerated and induced substantial
bronchodilation and bronchoprotection in the asthmatics. The present study assessed tolerability and
consistency of bronchodilator responses to inhaled RPL554 given on 6 consecutive days.
Methods: In a single-blind randomised placebo study, 12 clinically stable mild-to-moderate allergic
asthmatics males (age: 19-52 years; BMI: 20-27 kg/m2; FEV1: 2.9-5.1 Litres; FEV1: 75-104% pred. FVC:
4.2-7.0 Litres; FEV1/FVC: 56-90%; PEF: 7.1-13 Litres; PC20Mch: 0.10-6.1 mg/mL) not requiring controller
nor regular bronchodilator therapy were studied. The tolerability and bronchodilator effects of inhaled
RPL554 given daily at 0.018 mg/kg for 6 days was investigated using standard safety measures (i.e., heart
rate, blood pressure and ECG), pharmacokinetics (i.e., Cmax, AUC, T1/2), and spirometry (i.e., FEV1, PEF)
on days 1, 3 and 6 at the same time and compared to placebo measured at day -1 only. Study medication
was administered over a 10 minute period by a calibrated electronic nebuliser and oro-nasal mask.
Results: The 6 days of treatment were well-tolerated with a few mild and short lasting minor adverse events
reported. The most frequent were headache, irritation of the larynx and dryness of the throat. Heart rate and
blood pressure did not change consistently with minor changes in heart rate and diastolic blood pressures at
day 6. RPL554 drug retained its effect on FEV1 and PEF over the whole treatment period. The maintained
effectiveness of RPL554 was shown by the maximum increases in FEV1, as compared with day-1
responses, were which were 555, 505 and 485 mL, respectively for days 1, 3 and 6. The only statistical
difference was between days 1 and 6 (p=0.031 by Least Squares Mean), but the overall pattern was for a
clearly maintained effect. The PEF values remained comparable over study days 1, 3 and 6.
Pharmacokinetic evaluation of concentrations of RPL554 in plasma showed limited, non-consistent changes
in terms of Cmax, AUC, T1/2, indicating no major changes in systemic accumulation or metabolism.
Conclusions: In mild-to-moderate allergic asthmatics, daily doses of nebulised RPL554 for 6 consecutive
days were well-tolerated and produced consistent bronchodilation without any accumulation or altered
Am J Respir Crit Care Med 187;2013:A3875
For further information please contact:
Verona Pharma plc Tel: 020 7863 3300
Clive Page, Chairman
Jan-Anders Karlsson, CEO
WH Ireland Limited Tel: 020 7220 1666
FTI Consulting Tel: 020 7831 3113
About Verona Pharma plc
Verona Pharma is developing first-in-class drugs to treat respiratory disease, such as COPD, asthma and
chronic, severe cough. The Company has three drug programmes, two of which are in Phase II. The lead
programme, RPL554, is an innovative dual phosphodiesterase (PDE) 3 and 4 inhibitor with both
bronchodilator and anti-inflammatory properties. VRP700 is an innovative product for suppressing chronic,
severe cough in patients with underlying lung disease. In its third programme, Verona Pharma is
investigating novel anti-inflammatory molecules, called NAIPs, for a wide range of respiratory and
About RPL554 for the treatment of COPD and Asthma
Verona’s lead drug, RPL554, is a dual phosphodiesterase (PDE) 3 and 4 inhibitor being developed as a
novel treatment for chronic obstructive airways disease such as COPD and asthma with bronchodilator and
anti-inflammatory effects. Both effects are essential to improve symptoms in patients with COPD or asthma.
RPL554 is currently in phase II for both diseases.
COPD is a chronic lung disease with significant unmet need for which current treatment is far from optimal,
as it often has unwanted side-effects and/or limited effectiveness. COPD is most commonly characterised by
fixed airflow obstruction and chronic airways inflammation resulting from exposure to irritants like tobacco
smoke. Asthma, which remains one of the most common chronic diseases in the world, is characterised by
recurrent breathing problems and symptoms such as breathlessness, wheezing, chest tightness, and
coughing. The market for COPD and asthma drugs is estimated to be £20 billion [source: visiongain].
About VRP700 for the treatment of Cough
VRP700 is Verona Pharma's lead drug compound for the treatment of cough, having a novel mechanism of
action involving the suppression of cough initiating signals originating from cough sensory nerve endings
located in the lungs. A clinical trial completed at the University of Florence, Italy in September 2011 clearly
demonstrated significant anti-tussive effects with nebulised VRP700 in hospitalized patients with chronic
Cough can be a very debilitating comorbidity reported by patients, especially those with respiratory
conditions such as asthma, COPD, lung cancer, interstitial lung disease, fibrosis or lung infections. It is a
neglected symptom which is often self-medicated. Consumer spending on OTC medications, including those
for cough, grew by 10% over 2005-10, to reach GBP532 million [source: Mintel]. However, there is very little
clinical evidence for such OTC cough medications being really effective and it is widely recognised by the
medical community that there is a large need for more effective drugs to control and prevent pathologically
Help employers find you! Check out all the jobs and post your resume.