Verona Pharma plc
("Verona Pharma" or the "Company")
Interim results from new RPL554 trial demonstrates excellent drug tolerability
even at highest dose
Single ascending dose study in 50 healthy volunteers up to a dose that was
16 times greater than the previously used bronchodilator dose
Well tolerated without an effect oncardio-vascular parameters and without nausea or
vomiting at any dose
Results support twice daily dosing with this new formulation of RPL554
23 March 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 interim results from the first part of a 120
subject Phase I/II clinical trial with RPL554, using a new proprietary
nebulised formulation. RPL554 is a novel PDE3/4 inhibitor, which is currently
in development as a nebulised treatment for acute exacerbations in COPD
patients in a hospital or home-care setting.
The trial is being performed at the Medicines Evaluation Unit in Manchester by
lead investigator Professor Dave Singh.
In the first part of this study, which was successfully completed ahead of
schedule, 50 healthy volunteers were enrolled in a single ascending dose study
with the new drug formulation. Five dose levels were tested with the
pre-specified highest dose being approximately16 times greater than the dose
tested in earlier reported clinical studies, using the previous formulation of
RPL554.
The results from this study showed that the drug was well tolerated across all
doses and no maximum tolerated dose could be defined. Importantly, there were
no changes in subjects' cardiovascular parameters and there was complete
absence of nausea or vomiting at all doses.
Pharmacokinetic data showed lower peak plasma levels of the drug and a plasma
half-life of 11-12hr, significantly longer than that of historically published
data of similar doses, using the previous formulation. This suggests that the
new formulation results in a longer residence time for RPL554 in the lung and
slower release into the blood stream. Pulmonary residence time is an important
factor in determining duration of effect.1 These results support the potential
for RPL554 to be a drug administered twice-a-day and this will be further
verified in the second part of the trial, which is now being initiated.
In the next part of the study, multiple ascending doses given for five
consecutive days will be investigated in both healthy volunteers and patients
with chronic obstructive pulmonary disease (COPD). The primary objective of
this study is to further confirm safety and tolerability, as well as to
investigate bronchodilation in COPD patients. In studies with the previous
formulation, RPL554 generated significant bronchodilation that appeared to be
at least similar in effect size to that seen with salbutamol,2 a commonly used
drug in the treatment of COPD. Results from this new study are expected to be
available in the second half of 2015.
Dr Ken Newman, Chief Medical Officer of Verona Pharma,commented:
"These initial results are very encouraging and confirm that the new
formulation of RPL554 has excellenttolerabilityand hasa significantlyimproved
profile in comparison to the previous formulation. This has alloweddoses of
RPL554 to be assessed that are many multiples higher than doses tested in the
clinic to datethat have already demonstrated a robust bronchodilator effect.It
is important to note that even at the highest dosenow evaluated we have seen no
impact on subjects' cardiovascular parameters. No vomitingor evidence of nausea
has been reported. Additionally, the initial pharmacokinetic data suggests
aprofile that we tentatively believe could make RPL554 amenableto
twice-a-daydosing.We look forward to reporting data from the second part of
this trial in the second halfof 2015,which we expect will confirm the
potentbronchodilatorpotentialof thisdrug in COPD patients."
Dr Jan-Anders Karlsson, Chief Executive Officerof Verona Pharma, said:
"We are very excited by this first set of clinical data generated with our new
proprietary formulation for nebulised RPL554,which is consistent with the
expected profile based on preclinical studies. We have already demonstrated in
earlier trials that RPL554 has the unique ability to combine potent
bronchodilation with broad anti-inflammatory activity in a single molecule. The
studies we are now commencing, thanks to the excellent tolerability of our new
formulation, will allow us to assess markedly higher doses of the drug than
those used in our studies in COPD patients to date and seeks to maximise the
clinical impact of the drug. We look forward to reporting datafrom this
important clinical study later in the course of2015.
"We are initially developing nebulised RPL554 as a treatment for acute
exacerbations in COPD,where we believe it has significant market
potential.Wecontinue to believe that the emerging profile of RPL554suggests
that it could potentially become an important addition to available treatment
optionsboth 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 proof of concept studies with RPL554 in its previous
nebulised formulation were successfully conducted in over 100 subjects. Results
collectively showed that the drug is a very potent bronchodilator with the
ability to elicit a unique anti-inflammatory response. At the doses previously
tested, RPL554 had a benign side effect profile, which compared favourably with
existing standard treatments. The original nebulised formulation of the drug
used in these initial 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 patients, implying that they should
be able to inhale higher doses with prolonged effect, 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.
-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.
Bronchodilating therapy is considered to be the standard of care, and agents
can be administered via handheld devices such as metered dose inhaler (MDI),
dry powder inhaler (DPI) and by nebulisers. The nebulised bronchodilator market
was worth about $1 billion in 2014 in the US.3 RPL554 is being developed by
Verona Pharma as an add-on therapy to the "Standard of Care" with the
objectives of providing rapid and pronounced improvement in lung function,
reduced symptoms and both shortened duration of hospital stays and reduced
re-admission rates 30 days after discharge from hospital. Studies to date on
RPL554 have demonstrated that it has a strongly differentiated 3-way mode of
action, being: (1) bronchodilation (the relaxation of smooth muscle in the
airway); (2) anti-inflammatory effects on cells and (3) ion channel activation
in epithelial cells, with increased mucociliary clearance of the airway.
1 Olsson et al, in bvgH.D.C. Smyth and A.J. Hickey (eds.), Controlled Pulmonary
Drug Delivery, 21
Advances in Delivery Science and Technology, DOI 10.1007/978-1-4419-9745-6_2,
© Controlled Release Society 2011
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.
3 IMS Consulting Group market research 2014