Verona Pharma plc
("Verona Pharma" or the "Company")
Positive
headline data from RPL554 clinical study in COPD patients
New suspension
formulation is well tolerated; results signal marked improvement in
lung function
RPL554 remains on track for entry
into Phase IIb clinical trials in 2H 2016
29 September 2015, Cardiff
– Verona Pharma plc (AIM: VRP.L), the drug development company
focused on first-in-class medicines to treat respiratory diseases,
today announces encouraging positive headline data of the third and
final part (part C) of a randomised, double blind, placebo
controlled Single Ascending Dose (SAD) / Multiple Ascending Dose
(MAD) clinical study in stable chronic obstructive pulmonary
disease (COPD) patients. This study uses a new proprietary and
commercially scalable nebulised suspension formulation of the
Company’s lead pipeline drug, RPL554.1,2 The primary
objective of this part of the study was to show the safety and
tolerability of the new drug formulation in stable COPD patients
with moderate severity of disease.3 Measurement of lung
function using FEV14 was included. Evaluation of the
full data set is ongoing and will be presented in an appropriate
scientific, peer-reviewed forum at a later date.
Highlights: Part C of study in 32 stable COPD patients with
moderate disease severity3
- Primary objective of study met: Drug formulation well tolerated
at all dose levels; No serious adverse events reported
- Adverse event profile similar to that seen with placebo
- Absence of gastro-intestinal or cardiovascular adverse
events
- RPL554 caused pronounced improvement in lung function
- Mean peak FEV1 increase ranged from 199ml to 257ml versus
placebo
- Extent of bronchodilation exceeds that seen in earlier studies
with original proof of concept formulation
- Data continue to support twice daily dosing regimen with
RPL554
- Data consistent with that from earlier part A and B of study in
healthy volunteers
- Evaluation of the full data set from this trial is ongoing
In the third part of the trial, nebulised RPL554, a novel dual
PDE3/PDE4 inhibitor, was administered twice daily using a new
proprietary, commercially scalable, suspension formulation to
stable COPD patients with moderate disease severity for up to
five-and-a-half consecutive days at doses significantly in excess
of the previously used active dose. Patients withheld their regular
bronchodilator therapy for the duration of the treatment phase of
the study.
The study met its primary objective and all doses of RPL554 were
found to be well tolerated. As with earlier parts of the trial,
which were conducted in healthy volunteers, there were no reports
of serious adverse events and the adverse event profile was similar
to that seen with placebo. In particular, there was an absence of
gastro-intestinal or cardiovascular adverse events.
Lung function, as measured by peak FEV1, was increased in all
dose groups and ranged between 199-257ml over placebo suggesting a
clinically meaningful bronchodilator effect which will be confirmed
in Phase IIb studies. In the highest dose there was a small
increase in heart rate as might be expected from the pharmacology
of the product.
The new commercially scalable formulation of RPL554 results in a
uniform suspension of RPL554 and was designed to provide improved
tolerability, allowing higher doses of RPL554 to be inhaled,
yielding an optimised bronchodilator effect than with the previous
prototype, solution formulation. Additionally the new formulation
offers potential for improvements in convenience and compliance.
Data to date supports this profile, suggesting a twice daily dosing
regimen and is consistent with a longer residence time of the drug
in lung tissue and slower release into the blood than with the
original formulation. In addition, the commercial viability of the
new formulation is underlined by significantly improved stability
compared to the previous formulation.
Professor Dave Singh of the
Medicines Evaluation Unit, University of Manchester, lead
investigator on this study, commented: “I am very encouraged
by the headline results of this study using the new suspension
formulation of RPL554. The marked improvement in lung function seen
in this initial small study shows that this product has potential
to be a meaningful addition to existing treatment options for
COPD.”
Dr. Jan-Anders Karlsson, Chief
Executive of Verona Pharma, said: “We are excited by the
robust and consistent results arising from our SAD/MAD study of
RPL554 in both healthy volunteers and now, stable COPD patients
with moderate disease severity. The data demonstrates that, as
designed, the new commercially scalable, suspension formulation is
well tolerated and has allowed us to extend the dose range and the
duration of bronchodilation effect that can be produced in COPD
patients. We will now fully analyse the data from this trial. While
we need to discuss these results and confirm our further
development plans for the drug with the appropriate regulatory
authorities, we currently expect to begin Phase IIb studies in the
second half of 2016.”
RPL554 is currently in development as a nebulised treatment for
acute exacerbations in COPD patients in a hospital or home-care
setting. The nebuliser bronchodilator market was worth about
$1 billion in 2014 in the
US.5 RPL554 also has potential as a novel drug for the
maintenance therapy of COPD, for patients with asthma and cystic
fibrosis.
Phase I and Phase II studies with RPL554 in the previous
nebulised solution formulation were successfully conducted in over
100 subjects.6 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 the development of a new
formulation suitable for commercial scale-up.
-Ends-
For further information please
contact:
Verona Pharma plc |
Tel: +44 (0)20 3283 4200 |
Jan-Anders Karlsson, Chief Executive
Officer |
|
|
|
N+1 Singer |
Tel: +44 (0)20 7496 3000 |
Aubrey Powell / Jen Boorer |
|
|
|
FTI Consulting |
Tel: +44 (0)20 3727 1000 |
Julia Phillips / Simon Conway |
|
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
(“MEU”)
The Medicines Evaluation Unit 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 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.
References
1 See www.clinicaltrials.gov - ClinicalTrials.gov
Identifier:NCT02307162
2 Initial data from Part A and B for this trial were
reported in Company press releases dated 23
March 2015 and 8 June 2015
3 GOLD Stage 2 with no requirement for bronchodilator
reversibility:
http://www.goldcopd.org/uploads/users/files/GOLD_Report_2015_Sept2.pdf
4 FEV1: forced expiratory volume in one second
5 IMS Consulting Group market research 2014
6 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