Verona Pharma plc
("Verona Pharma" or the "Company")
RPL554 MAD study in healthy
volunteers confirms excellent tolerability;
dosing of COPD patients commences
Multiple 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
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
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.