Drug development in an innovative model of collaboration between academia and industry

Professor Sir Mark Pepys and his team in the UCL Wolfson Drug Discovery Unit have invented new chemical entities for treatment of amyloidosis, Alzheimer's disease, and other conditions. GlaxoSmithKline has licensed some of the patents and is developing them for clinical use in interactive collaborations with the expert academic team.

Proteins perform a very wide range of essential functions in the body, after which they are normally recycled or destroyed. However, occasionally, and especially with ageing, some proteins transform into abnormal insoluble fibres, called amyloid fibrils, which accumulate in the spaces between the body's cells. Amyloid deposits disrupt the structure and function of the affected tissue and, if they are widely distributed, they cause the disease called systemic amyloidosis. This rare but serious condition is usually fatal and is responsible for about one per thousand of all deaths in developed countries. There are about 6,000 systemic amyloidosis patients in the UK with commensurate numbers across the developed world and potentially more pro rata in the developing countries. Treatments exist for only some forms of systemic amyloidosis and the therapies are toxic, expensive and often of limited efficacy. Crucially no existing intervention directly targets the amyloid itself.

Professor Pepys has worked on amyloidosis for 40 years. He established the UCL Centre for Amyloidosis and Acute Phase Proteins when he joined UCL in 1999. The Centre includes the UK NHS National Amyloidosis Centre, funded by the Department of Health to provide diagnostic and management advisory services for all patients with amyloidosis in the country. Despite the Centre's world-leading expertise, amyloidosis remains an important unmet medical need.

Development of new medicines is one of the slowest, most complex and most expensive of human activities. It is clearly beyond the skills and resources of a university, although the scientific and clinical knowledge, which identifies targets for new medicines, resides mostly in academic institutions. Bringing together the disparate resources and capacities of academia and big pharma productively is currently an evolving process with deployment of different strategies by different companies. Our collaboration with GSK has been exhilarating, especially after decades of working on amyloidosis, a rare but terrible disease for which effective treatments are very limited and challenging. There is no greater reward than testing our ideas in patients and seeing them produce clinical benefit. It is also a reward for the taxpayer as my research has been funded by the MRC without interruption since 1969, along with generous support from the Wolfson Foundation, The Wellcome Trust and other medical charities. - Professor Sir Mark Pepys

Professor Pepys first devised a novel approach to possible treatment of amyloidosis in 1984. In the 1990s he worked with Roche to develop a novel small molecule drug, CPHPC, which he designed to target a normal blood protein called serum amyloid P component (SAP). SAP binds specifically to all amyloid fibrils but although CPHPC remarkably removes SAP from the blood, it fails to remove all SAP from systemic amyloid deposits. Patients receiving CPHPC remained clinically stable but their amyloid deposits did not regress. In 2005 Pepys devised a further novel approach, in which prior treatment with CPHPC, to clear SAP from the blood, is followed by administration of antibodies against SAP to target the amyloid deposits in the tissues. In experimental models this approach produced dramatic elimination of amyloid deposits from vital organs and in 2009 GlaxoSmithKline licensed the Pepys patents for clinical development.

At the same time, instead of just acquiring IP and developing it themselves, GlaxoSmithKline pioneered a novel collaborative arrangement for drug development with academia. Intensive interaction optimally leverages the respective strengths and competence of both parties: the unique specialist knowledge, scientific research expertise and well-characterised clinical populations of the academic partner, and the outstanding drug development capabilities of a major international pharma company. GSK aimed to recruit selected university scientists and clinicians into such programmes and identified Professor Pepys as their first "academic superstar".

The collaboration has proceeded very effectively, yielding new IP, and the production and regulatory testing of the synthetic and antibody drugs before use in man. Following phase I studies in healthy subjects, efficient recruitment of patients from the National Amyloidosis Centre enabled an effective regulatory phase I study of CPHPC in amyloidosis patients. This set the stage for the phase I study of anti-SAP antibodies following CPHPC administration which is currently in progress.

The results so far are very encouraging. The treatment is well tolerated and has produced unprecedented reduction in amyloid deposits in vital organs, associated with improvement in organ function. The first publication of these findings is about to be submitted for publication. Success has been recognised by GSK's award of the Clinical Proof of Mechanism Milestone. Furthermore the new treatment has received orphan drug designation by the European Medicines Agency, and also been adopted as a potential candidate for Adaptive Licensing, a new regulatory procedure to accelerate availability of new drugs for unmet medical needs. The ability to directly target amyloid is a potentially powerful new approach to the treatment of this debilitating and usually fatal disease.

The transmission of drug discovery directly from a university into big pharma is a very rare achievement. The present case reflects GSK's insightful recognition of the unique, critical contribution of original, creative university scientific and clinical research, and then harnessing it synergistically to the diverse skills, enormous resources and powerful capacity of a major pharmaceutical company.

Related links

• UCL Centre for Amyloidosis and Acute Phase Proteins
• UK NHS National Amyloidosis Centre
• SAP Depleter Dose Assessment Study in Patients
• A Study to Evaluate the Safety of GSK2398852 When Co-administered With GSK2315698 in Patients With Systemic Amyloidosis
• European Medicines Agency orphan drug designation for treatment