Challenges in Drug Discovery
Ian A Cliffe, MA PhD CChem FRSC
Vice President and Head, Research Management
Daiichi Sankyo India Pharma Private Limited
Village Sarhaul, Sector 18, Udyog Vihar Industrial Area, Gurgaon 122 015, Haryana, India
The pharmaceutical industry can rightly be proud of its many triumphs in the twentieth century which have improved quality of life and led to greatly increased life expectancy. In more recent times, the industry can point to successes in improving cancer survival rates and achieving a near normal life for HIV sufferers.
However, the industry has been facing a number of unprecedented challenges including poor stock performance as revenues decrease and “blockbuster” drugs go off-patent. Low productivity and a lack of new drug candidates is the result of weak early-stage and late-stage pipelines. The regulatory environment is increasingly stringent and requires pharmaceutical companies to carry out large, expensive and often complex clinical trials to prove that the efficacy and safety of a potential new drug is superior to the current standard of care.
To exacerbate such matters, it is well documented that drug discovery and development is a high risk endeavour, taking a long time (> 12 years), having a high attrition rate (only 1 out of 10,000 new chemical entities ever makes it to market) and being very expensive. According to a new report by the Pharmaceutical Research and Manufacturers of America, 1 the cost of creating a novel drug is now estimated to be USD 2,600 Mn.
The good news is that the number of new drugs sanctioned by the US Food and Drug Administration has increased in the last three years and reached a 20-year high of 45 approvals in 2015.
A key factor in the turnaround of pharmaceutical fortunes is the better appreciation of the reasons for drug development failures. AstraZeneca identified the root causes of attrition in its small-molecule R&D projects in a ground-breaking retrospective examination of data and decisions it made between 2005 and 2010. 2 The analysis provides a “5R framework” for effective decision making, project success and pipeline quality based on the five technical determinants of “Right Target”, “Right Tissue”, “Right Safety”, “Right Patients” and “Right Commercial Potential”. The framework allows AstraZeneca to predict pharmacokinetic/pharmacodynamic properties of molecules, enhance understanding of not only “right tissue” but also “right molecular target” and “right safety”, and improve appreciation of the payer and reimbursement environment.
A second major factor behind the recent productivity enhancement is the realization that no single company in this day and age can “go it alone”. For pharmaceutical companies, the need to understand the pathogenesis of human disease and to identify and validate novel therapeutic targets has led them to collaborate increasingly with academic partners. For the treatment of diseases which primarily affect people living in the developing world there has been a marked upturn in the number of public-private partnerships co-funded by national governments, international agencies, pharmaceutical companies, and/or philanthropic foundations. These enterprises are often networked on a global scale and include the Medicines for Malaria Venture,3 the Tuberculosis Alliance,4 and the Drugs for Neglected Diseases Initiative.5
Looking forward, novel advances in treating disease will come from cutting-edge science and discoveries using synthetic biology, chimeric antigen receptor (CAR) T-cells, biochips, tissue engineering, 3D bio-printing and the exciting CRISPR/Cas9 for targeted gene editing. The efficient exploitation of new technologies for the good of patients will require sustained coordination between industry, university and government bodies. As the African proverb says, “If you want to go fast, go alone. If you want to go far, go together.”
2 David Cook, Dearg Brown, Robert Alexander, Ruth March, Paul Morgan, Cemman Satterthwaite and Menalas Pangalos, Nature Reviews Drug Discovery, 2014, 13, 419-431.Previous Post Next Post