Metrion Biosciences’ July 2018 External Speaker Event provided insight into the pitfalls of modern medicines discovery and the “disruptive influences” associated with drug discovery and development. The presentation was given by Professor Trevor Jones CBE, Visiting Professor, King’s College London and former Director General of the Association of the British Pharmaceutical Industry (ABPI). Trevor’s highly distinguished career has allowed him to evaluate the drug discovery and development process from various perspectives, having served on a number of national and international commissions and acted as a main board Director of the Wellcome Foundation where he was responsible for the development of medicines such as AZT, Zovirax, and Malarone. Trevor was also a founder of the Geneva-based public:private partnership Medicines for Malaria Venture (MMV). Trevor gained the prestigious award of CBE in the 2003 New Year’s Honours List.
Trevor’s presentation, the eighth in Metrion Biosciences External Speaker Series, comprised an initial appraisal of the drug discovery process as generally adopted today and he expanded on the need for a more thorough evaluation and validation of the target at the pre-clinical stage, to shift attrition before significant amount of money has been spent across a number of disciplines. He spoke of the leveraged savings from moving emphasis to early phase discovery and the reasons for the high number of drug failings, which includes lack of a full understanding of complex disease targets, poorly-selective compounds and associated off-target effects, manufacturing and IP issues and suboptimal pharmacokinetics, dynamics and metabolism.
Trevor elaborated on how Research and Development (R&D) expenditure has continued to rise, with only a relatively small increase in actual productivity. Accelerating Medicines Partnerships (AMP), involving large pharma companies, have been established for diseases such as Alzheimer’s Disease, Schizophrenia, Type II diabetes and rheumatoid arthritis. Trevor has been involved in such initiatives for some time and he emphasised the importance of such data sharing and product development partnerships to improve the chance of development new therapies for diseases with significant unmet need (e.g. cancer) and those prevalent in the developing world such as malaria, dengue fever, rotavirus and Chagas disease. Trevor also touched upon the importance of new initiatives to involve patients and carers in the development process, to establish potential the quality of life, issues with compliance and effectiveness of new medicines. With such initiatives involving inputs from social media channels, employers, the media, thought leaders, government agencies and advocate organisations.
The presentation then moved on to the topic of cancer as a heterogenous and a genomic disease and the importance of understanding the roles of genes and associated mutations, with the complex cancer cell division network; pointing out that finding compounds that hit “single targets” are unlikely to be therapeutically successful. Approaching cancer therapy from a genomic disease standpoint, rather than a purely symptomatic perspective will undoubtedly revolutionise therapeutic options across a range of tumour types.
Trevor then turned to the Alzheimer’s Disease drug development pipeline, where despite the vast sums of money spent on R&D there are still no effective disease-modifying drugs on the market. As the sixth leading cause of death in the US, greater than breast and prostate cancer combined, and with an ageing global population there is clearly an overwhelming need for efficient medicines to treat Alzheimer’s Disease. With the objective of identifying effective disease-modifying drugs various consortia have now been established, such as the Global CEO Initiative. By forming robust public- private partnerships to pursue research, therapy development, financing, and public awareness projects it may be possible to learn from the past failed approaches and clinical trials and, if successful, transform the global fight to stop Alzheimer’s disease.
In a more general evaluation of the drug discovery landscape, Trevor highlighted the importance of data sharing and full exploitation of new advanced treatments, including CAR-T and other immune cell therapies for cancer. This is clearly an area with rich potential for novel medicines development; with, for example, 22 different cancer types targeted by new active substances since 2011. There is also a need to address the ethical and wider use of gene therapy and gene editing (including CRISPR-Cas 9), these novel treatments may be associated with as yet undiscovered safety and efficacy issues, requiring extreme caution during the development process.
Trevor also discussed recent developments in artificial intelligence / machine learning and, whilst potentially a step change in the drug discovery arena, the need to proceed with extreme caution to ensure the output is based upon solid data foundations. Nevertheless, with recent advances in computational technology there is great potential to integrate data from multiple sources (clinical, cellular, disease models), merging this with biological insight to identify the key components in a disease pathway, followed by application of in silico screening techniques to identify compounds with the highest potential impact.
Another paradigm raised during the presentation was that of Digital Health, defined by Trevor as “the convergence of the digital and genomic revolutions with health, healthcare, living, and society”. Sensor innovation is clearly driving Digital Health, with smart inhalers for asthma, wrist and chip-based cardiac monitors, blood sugar monitors and ingestible gastro intestinal sensors the size of a pencil tip. These technologies enable “Distance Medicine” whereby sensor information and mobile data technologies enable consultation with a qualified physician using a mobile phone or tablet. With the time pressures and constraints associated with modern day living, in ten years’ time, it is anticipated that only 2% of consultations will take place at a GP surgery. Combined with internet pharmacy companies, Digital Health promises more informed diagnosis, with reduced demands on patient time.
The overwhelming conclusion of the presentation, and subsequent discussion, appeared to be the need to introduce change into the R&D process and embrace novel and modern approaches and therapies where appropriate, being mindful of associated risks. This change is not a choice and we must move with the times, liaising directly with the patient and companies should address their business model to ensure they are offering cost and time effective solutions whilst maintaining awareness of developments in healthcare and biology.
Metrion Biosciences’ External Speaker Series was established as a forum for leading academic researchers to present their latest research to our staff and staff from other companies in the Cambridge area. The Metrion team welcomes suggestions for future speakers and topics via: this link.
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