A routine test to screen for patients genetically disposed to serious
side effects from treatment with thiopurine drugs has been widely adopted
following research by the Academic Unit of Clinical Pharmacology at the
University of Sheffield. The test has spared patients painful and
potentially life-threatening sepsis, and saved the considerable associated
treatment costs which have been estimated to be over £9,000 per patient
for a 17 day hospital stay. It has also led directly to a change in
clinical guidelines and recommendations in both the USA and UK.
Innovative formulation science to create and develop the commercially
successful PowderHale® technology was undertaken within the
Department of Pharmacy & Pharmacology at the University of Bath, and
subsequently by Vectura. This has directly provided the basis for novel,
potentially life-saving treatments for chronic obstructive pulmonary
disease (COPD). Seebri® Breezhaler® and Ultibro®
Breezhaler® are once-daily, maintenance bronchodilators for the
relief of various symptoms due to airways obstruction caused by COPD.
Seebri® Breezhaler® was approved in the EU and Japan
at the end of 2012 and has now been launched by Novartis. Ultibro®
Breezhaler® a first-in-class combination bronchodilator was
approved in Japan and the EU in September 2013. Under the terms of the
licence agreement with Novartis concerning these products, Vectura has
already received $52.5M with an additional >$100M anticipated upon
achievement of regulatory and commercialisation targets. These medicines
are major advances to treat and manage a disease that, according to the
WHO, affects an estimated 210 million people worldwide and was the third
leading cause of death in the developed world in 2012.
Clinical pharmacology studies conducted at Newcastle have led to
optimisation of the administration of the chemotherapy drug carboplatin in
children with neuroblastoma and other cancers. The research provided the
rationale for carboplatin dosing based on patient renal function, with
individualised dosing resulting in increased drug efficacy and reduced
toxicity. This approach is now in widespread use in national and European
treatment protocols, benefitting over 2,500 children. Similar drug
monitoring approaches are being implemented for an increasing number of
important drugs. Following a recent Newcastle-led national clinical trial,
new dosing guidelines for the drug 13-cis retinoic acid have been
adopted for high-risk neuroblastoma patients across Europe.
The development of new paradigms for toxicity testing has benefitted the
Scottish economy and population in Tayside through two biotechnology
companies which, between them, employ up to 40 staff and have had a
combined turnover of some £15M over the last five years. The benefits
extend to the international pharmaceutical, cosmetic, chemical and
consumer product industries, which have gained access to innovative new
methods for safety testing at a time of acute need for more predictive
methods to evaluate drug safety and better in vitro tests for
consumer products. Patients and consumers in Europe and worldwide have
benefitted indirectly from improved risk assessment of drugs, consumer
products and environmental contaminants.
A new, more structured way of assessing the various harms done to
individuals, families, communities and wider society by a range of legal
and illegal drugs was first articulated by Professor David Nutt and
colleagues at the University of Bristol. The "rational scale" they
developed in the light of their research has stimulated extensive policy
debate and informed drug classification in the UK and overseas. The
research underpinning the scale has been disseminated through numerous
public lectures and discussions and has stimulated worldwide media
coverage. As a consequence, public awareness of drug harms has increased
and public engagement in important debates about drugs has intensified.
Research by Professor Abdul Basit's group at the UCL School of Pharmacy
is leading to improved treatments for ulcerative colitis and other
conditions through increased knowledge of the complex physiology of the
gastrointestinal tract. Improved understanding of in vivo drug
release and uptake has allowed development of three patent-protected
technologies for improved drug delivery: PHLORALTM, for release
of drugs in the colon, and DuoCoatTM and ProReleaseTM
formulations designed to allow intact transit through the stomach followed
by immediate release upon gastric emptying. These technologies are the
subject of licences and ongoing development programmes, with PHLORALTM
currently in phase III clinical trials. The impact is therefore
the introduction of enabling technologies that have positively influenced
the drug development programmes of pharmaceutical companies.
Drug development is a highly regulated environment. Identifying the need
for an independent, academic-led centre of excellence in research and
training of pharmacokinetics, we established the Centre for Applied
Pharmacokinetic Research (CAPKR) to engage in problems of generic interest
to the Pharmaceutical Industry. CAPKR has been highly influential by
informing regulatory practice in Europe and the USA, by establishing and
optimising industrial practices related to drug development, particularly
those related to drug-drug interactions, by reducing the usage of animals
in research and by allowing the commercial development and extensive use
of simulation software tools for quantitative prediction of
pharmacokinetics in order to improve patients' safety.
Research by the School of Pharmacy played a key role in the 2008
regulatory approval of Janssen Pharmaceutica's HIV drug Intelence®.
As a poorly soluble drug, Intelence® required specialist
formulation and was the first formulation of its type to be approved by
the FDA and EMA. Intelence® offers significantly improved
clinical outcomes due to its efficacy in patients with HIV resistance.
Global Intelence® sales in 2012 were $349M, with additional
not-for-profit supplies to resource-limited countries. As a result of this
landmark regulatory approval formulation development strategies at Janssen
were adapted enabling a further poorly soluble drug to reach the market.
Telaprevir, a second-generation Hepatitis C treatment (marketed as Incivek®,
Incivo® & Telavic®), gained global regulatory
approval in 2011. 2012 sales exceeded $1bn in the US alone.
This research has had impact on two linked areas of illicit drug policy.
Firstly, pioneering research on the effects of drug decriminalisation in
Portugal has shifted the debate on this issue in the UK, US and elsewhere
towards an acceptance that decriminalisation is a viable and not harmful
approach. Secondly, research on alternatives to imprisonment for
drug-dependent offenders has moved debate towards supporting the expansion
of treatment for such offenders in the UK and US. These impacts are
evidenced in the citation of the research by policy-makers and NGOs
(including the British Sentencing Advisory Panel; The All Party
Parliamentary Group on Drugs; the Home Affairs Select Committee; UK NGOs,
Release and Transform; the US Drug Policy Alliance and the United Nations
Office on Drugs and Crime), demonstrating a significant influence on
policy-making as well as public debate.
The university's Pharmacy and Pharmacology unit has developed and
validated novel in silico and in vitro/ex vivo models for
use by the pharma industry to select drug candidates, optimise
formulations, determine the posology for clinical trials and show
bioequivalence. This resulted in: the approval of two products for actinic
keratosis (Picato® and Zyclara®); a generic nail formulation approved for
use based on the demonstration of equivalence using the in vitro/ex
vivo models described with no clinical testing (the first time this
has occurred); and the translation and commercialisation of two dermal
drug delivery-based patented technologies (licensing deals with Sinclair
IS and major pharmaceutical companies).