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Labelled compounds form an essential part of drug discovery and development within the pharmaceutical industry. Novel iridium catalysts, developed by Kerr at WestCHEM since 2008, have introduced a step-change in the ability to label pharmaceutical candidate compounds with radioactive (tritium) or non-radioactive (deuterium) isotopes.
The catalysts are applicable to specific types of compounds that comprise approximately one-third of all drug candidates. Advantages of the catalysts include greater efficacy (less catalyst needed and higher yield of labelled product, giving cost savings), greater speed (efficiency savings), and a significant decrease in radioactive waste compared with previous methods (environmental and safety benefits).
Even since 2008, their adoption within the pharmaceutical industry has been extremely rapid; e.g., the multinational pharmaceutical company AstraZeneca now applies the Kerr methodology to 90% of their relevant candidate compounds. Additional impact has been achieved by Strem Chemicals who have been manufacturing and marketing the catalysts worldwide since October 2012. Even in that very short period, multiple sales have been made on three continents providing economic benefit to the company.
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.
Nearly all solid dosage forms contain drugs in crystalline form; and all crystals have the potential to `morph', suddenly, into different forms which can affect the safety and efficacy of the medicinal product. A number of high-profile cases in which marketed medicines had to be withdrawn [Lee, et al., Annu. Rev. Chem. Biomol. Eng. 2011, 2, 259-280] led multinational drug company Pfizer to conclude that a greater understanding of polymorphism was required to enable drug product design for the 21st Century. The University of Greenwich pioneered methods to predict crystal behaviour on the shelf and during manufacture that were affordable, timely and effective. It enabled Pfizer to select the optimal polymorphic drug form and manage risk associated with uncontrolled solid-state transformations, thereby safeguarding patients and avoiding huge costs.
Since 2008, pioneering contributions to the field of computational chemistry for drug discovery have been made by InhibOx Ltd., a spin-out company based on the research of Graham Richards and co-workers at the University of Oxford. InhibOx launched Scopius, the world's largest searchable virtual database of small-molecules (>112 million compounds) and pioneered the use of cloud computing for large-scale molecular modelling. The key impact for customers of InhibOx has been the reduced costs in identifying molecular leads for new drugs. InhibOx's work has helped to open up early stages of drug development to smaller companies; 75% of InhibOx's clients are SMEs. Since 2008, InhibOx has received £ 2.8M in income and investment.
Alzheimer's disease (AD) affects one in seven of the population over 60 years of age, and represents an increasing burden on worldwide medical and care resources. Treatments currently available are symptomatic. Despite pharmaceutical industry efforts there has been little indication of a marketable product for long-term treatment.
To address this problem, a joint venture was established in 2001 between the University of Aberdeen and TauRx Pharmaceuticals. A team was created of chemists, biologists, animal behaviourists, working together with a clinical trial team. A drug effective against the progress of AD based on the compound methylene blue was synthesised and scaled up within the Chemistry Department (led by Professor John Storey), with a quality that was proved acceptable through successful phase two clinical trials (2006-8), and is now used in phase three clinical trials which are due to complete in 2015. Several other drug candidates have also been developed and evaluated in pre-clinical and phase one clinical studies that show promise. Collaborations with commercial pharmaceutical companies have as a result led to the manufacture of significant quantities of drug medicines for TauRx Pharmaceuticals based on IP generated within the Chemistry Department and these drugs have been used in clinical trials and for named patient supply (c. 60 patients). This has resulted in increased commercial revenue for these companies and the creation of new employment.
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.
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.
Research by Professor Jones, Department of Chemistry, University of Cambridge, resulted in the development of a new method for preparing composite solids, involving the grinding of two or more crystalline solids in the presence of small volumes of liquid. This so called "liquid assisted grinding" (LAG) which produces novel solids with bespoke physical and chemical properties, is now routinely used by the major pharmaceutical companies to screen for new drug forms as part of their drug product development process.
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.
The health of people who inject illicit drugs, the formulation of harm-reduction policies, and the work of associated businesses and social enterprises have all benefited from the University's laboratory and practice research into the safety and efficacy of materials and equipment used in needle-exchange programmes. The research has informed the development of safer acids for injection preparation, safer injecting paraphernalia (e.g., spoons and filters) and an information film which has been distributed from needle exchanges on DVD and viewed over 50,000 times online. The research has led to enhanced support and protection for injecting drug misusers, and to advances in harm reduction in the UK, France and Canada.