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Dalgleish proposed a programme to develop thalidomide analogues for their immunomodulatory and anti-neoplastic actions. Working with a small start-up company, Celgene, several analogues including lenalidomide and pomalidomide were developed and entered clinical trials. Both drugs significantly prolong patient survival in myeloma and myelodysplasia and have received FDA and NICE approval for these purposes. Celgene has grown into a large multi-national company with over 5000 employees. Lenalidomide sales were $3.8 billion in 2012.
ProTide technology, discovered by the McGuigan team at Cardiff University, is a pro-drug strategy with proven capacity to generate new drug candidates for nucleoside-based antiviral and anti- cancer indications. In the assessment period the McGuigan team has attracted more than £2 million direct research funding through sustained collaborations on ProTide technology with global pharmaceutical companies and smaller biotech firms in the USA and Europe. In the same period, either through working directly with Cardiff or by independent adoption of McGuigan's research, eight ProTide entities have progressed to clinical trials as cancer, HIV and hepatitis C treatments. The technology is demonstrating significant commercial impact for companies with ProTide-based drug candidates.
A substantial programme of research carried out by LSHTM has provided evidence for a major shift of strategy and progress in global efforts to eliminate malaria. As a result, WHO now recommends a policy designed to ensure medically-treated individuals are non-infectious to mosquitoes. In addition, drug development partnerships such as the Medicines for Malaria Venture now include transmission interruption in the target product profiles for new medicines. Several countries have made strategic decisions for the prevention of malaria transmission on the basis of the research, and the senior investigators act as advisers to international anti-malaria initiatives.
LSHTM researchers carried out the initial trials of intermittent preventive treatment in infants (IPTi), a strategy to improve malaria control in very young children. LSHTM staff were active in setting up and running a dedicated research consortium which developed and executed a research agenda to provide data to inform policy. School staff presented evidence to a series of WHO policy-making meetings which in 2009 recommended that IPTi should be included as part of routine malaria control. This policy, which has been adopted in one country and discussed by eight others, has the potential to benefit hundreds of millions of lives.
Southampton research underpins the clinical development of a new class of anti-cancer monoclonal antibodies (mAb), such as anti-CD40, anti-CD27 and anti-CD20. The most advanced is a next generation, fully human drug, ofatumumab (commercialised by GlaxoSmithKline/Genmab; trade-name Arzerra) approved in Oct 2009 to treat advanced chronic lymphocytic leukaemia. Its approval was based on a 42% response rate in patients who had failed current `best in class' treatment. Arzerra is now a multi-million dollar drug, launched in 26 countries (and growing) and is being used in 19 on-going clinical trials worldwide for diseases ranging from lymphoma to rheumatoid arthritis and multiple sclerosis. Southampton's work has inspired follow-on funding from government and industry in excess of £12m.
Pioneering research led by the University of Aberdeen has directly resulted in the development of an investigational medicinal product for the long-term management and prevention of Alzheimer's disease, breaking new ground in the search for effective Alzheimer's treatments. Although not yet commercially available, this drug has already benefited more than 100 patients and their families. A new spin-out company created to develop the drug has created new jobs and attracted more than US$335 million in investment since 2008. Extensive media coverage of the research has generated increased public awareness of the disease and Aberdeen's cutting-edge research and ability to raise investment. The claimed impact is therefore that a new spin-out company was formed; investments from and collaborations with industry in research and development were generated; and new employment created.
Twenty years of comprehensive research into long-lasting insecticidal nets (LLINs) by LSHTM have contributed substantially to the prevention of around 1m deaths from malaria between 2008 and 2013. The research made a direct impact on guidelines and strategies issued by WHO as well as driving new technologies for insecticide-treated nets (ITNs), with downstream commercial benefits. Without the evolution of LLIN technology driven by LSHTM research, the large-scale roll-out of the new generation of nets (described in more detail in the other LSHTM impact case study on this body of research) would not have been possible.
Multidisciplinary research at LSHTM has increased understanding of how antimalarial drug resistance emerges and spreads, resulting in impacts on national, regional and international policy-makers and donors, and especially benefiting malaria patients and communities in Southeast Asia. The research influenced (1) WHO recommendations on using sulphadoxine-pyrimethamine for intermittent preventive treatment in Africa and (2) policy responses to the threat of artemisinin resistance including the WHO `Global Plan for Artemisinin Resistance Containment' (2011) and the Thai-Cambodia Artemisinin Resistance Containment programme (2009-2011). These efforts were associated with decreased malaria cases, and reduction in availability of artemisinin monotherapies in Cambodia.
The provision of effective and sustainable healthcare is a major challenge for society. In the developed world escalating costs are placing a huge burden on finite resources; in the developing world, where financial resources are often extremely limited, providing affordable healthcare is an even greater problem. One innovative route to help alleviate these problems is through drug redeployment, whereby existing drugs are employed in new ways to tackle serious diseases. Combining their knowledge of haematological disease gained from their research over the past 20 years together with a drug redeployment strategy, researchers in the School of Biosciences have developed and trialled new interventions for two blood cell cancers, Acute Myeloid Leukaemia (AML) and Burkitt's Lymphoma (BL), based on the administration of a combination of the lipid lowering drug Bezalip (Bez) and the female contraceptive Provera (MPA). As a result:
Psoriatic arthritis (PsA) is a chronic inflammatory disease of joints, skin and tendons that affects 0.5-0.8% of the population worldwide. PsA can cause substantial psychological and social problems and also causes increased risk of death from cardiovascular disease. Research conducted by Prof Iain McInnes at the University of Glasgow in partnership with leading pharmaceutical company, Janssen, has provided robust evidence of the clinical benefits and safety of the cytokine blocker ustekinumab, leading to its approval for use for PsA by the European Medicines Agency in July 2013. This was the first approval of a PsA drug with a new mode of action in a decade, providing a novel treatment for approximately 1.25 million PsA patients across Europe.