Redefining Cancer Drug Development: The Need for a New Roadmap from Discovery to Drug

Volume 17, Number 11, European Edition - November 2012

Redefining Cancer Drug Development: The Need for a New Roadmap From Discovery to Drug

William Hait

Global Head, Janssen Research & Development, LLC, Raritan, New Jersey, USA

Disclosures: The author indicated no financial relationships.


Cancer is a disease whose complexity requires a multidisciplinary approach to translate discovery science into clinical reality. Nowhere is this more pertinent than in the development of innovative medicines and targeted therapies for malignancy. There needs to be a fundamental shift in our approach to drug discovery and development, one which embraces a more functional intersect between academic science, clinical medicine and the pharma/biotech sector. This new approach requires a clear understanding of the medical need, coupled with the most compelling science to deliver meaningful innovations to patients in a rapid fashion. The molecular medicine revolution has dramatically accelerated our understanding of cancer biology, created significant expectations, and placed enormous pressure on our ability to translate these discoveries into effective treatments for patients. We need to respond to these challenges efficiently, articulating a clear vision and developing an innovative roadmap that allows us to "fast track" drug discovery and development, thus delivering clear benefit to the cancer patient. Our current drug development model is no longer "fit for purpose".

Realising the Promise of Targeted Therapy

As our understanding of cancer biology improves, the promise of targeted therapy looks set to be realised. Identifying appropriate targets and developing inhibitors to these targets allows the discovery pipeline to be accelerated, with more rapid progression from target identification to clinical validation. Parallelling the drug discovery and validation process is the development of companion diagnostics and predictive biomarkers, allowing more precise measurement of treatment efficacy in a selected patient cohort enriched to respond to the candidate drug. Understanding the target in its molecular context in the patient also provides valuable insights into drug resistance, helps identify new drugs that retain anti-cancer activity, and informs the design of more rational combination therapies. The targeted approach will ultimately deliver safer and more effective cancer medicines.

Re-Engineering Our Drug Pipeline Model; Developing a Fundamental Discovery to Product Delivery Partnership

Current estimates indicate that it costs between $1 billion and $2 billion and can take a decade to bring a drug from discovery to bedside. Given that there is an approximately 90% attrition rate of drugs entering the clinic, we clearly have an unsustainable model that requires significant re-engineering. While we currently concentrate on the target, a more comprehensive understanding of the disease process and, in particular, the disease context has the potential to yield more significant benefits and identify "better" drugs. Crucial to this premise is the accumulation of complementary expertise - we need to play to our individual strengths while maximising the added-value of a partnership-type approach. Collaboration can be a key enabler of more robust drug discovery and development models, and the "academia-pharma intersect" is an important arena for promoting new, flexible but resilient partnerships. In this partnership model, fundamental research should be driven by the academic sector, and the translation of this discovery science should be the remit of the pharma/biotech sector. A seamless translational continuum would underpin a "Fundamental Discovery to Product Delivery" partnership that would benefit academia, industry and, most importantly, the patient.

Obstacles to Progress: Funding and Regulatory Issues

If this "Discovery to Delivery" partnership is to succeed, it must be developed in a coherent fashion, involving all stakeholders and maximising collaborative added-value opportunities. So what are the obstacles to this model? There has been a significant shift in research policy and funding over the last number of years, moving away from the support of fundamental or basic research and concentrating on translational medicine. While we do need to fund and support this translational space, it should not be at the expense of fundamental science. While industry has to a large extent (rightly I think) moved away from performing fundamental research, it is critical that academia continues to perform discovery science and should be appropriately resourced to do so.

Making the Case for Continued Investment in Fundamental Research

Investing in science not only helps to save lives, it also makes economic sense. An effective new drug that significantly extends people's lives also improves their quality of life, thus making them more productive so that they contribute to the national economy through extra years of employment. In addition, costs associated with continued hospital/hospice stays are removed, thus reducing the overall cancer healthcare budget.

Another way to evaluate the link between research spending and economic benefit is to look at the cumulative research budget and link it to cumulative national increase in cancer patient survival. In the US, in the period 1988-2000, life expectancy for cancer patients rose by 3.9 years [1 ]. Evaluating the social value of this 3.9 year survival gain, Lakdawalla and colleagues at the Milken Institute estimated that the $300 billion cumulative spend on cancer research in this time period was reflected in a $1.9 trillion benefit to the national economy in terms of productive lives saved [1, 2 ]. Thus the benefits of R+D significantly outweigh the associated costs. In the European context, countries (e.g., Switzerland, Germany, France) that have invested significantly in cancer care, including research and innovation, have higher cancer survival rates [3 ].

Streamlining the Regulatory Approval Process

Another challenge that we face is the need to accelerate the regulatory drug approval process. Shortening the timeline between the start of the Phase III trial and registration of the drug is an important goal in this new era of stratified medicine and targeted therapy. This is particularly relevant as we look at more novel approaches to trial design. Hastening the pace through the research and regulatory pipeline will help bring new drugs and treatment options to patients more rapidly, and at far lower costs. Cooperation between the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) is an important component of this accelerated regulatory process. Recent initiatives that foster a culture of convergence between the FDA and EMA are to be welcomed.

Delivering Accelerated Translational Medicine

A comprehensive understanding of the disease process is crucial to drug discovery and development - we need to concentrate more on the disease, rather than exclusively focusing on the target. In any case, single-target therapy may not be the ultimate way to proceed, given the complexity of cancer and its multigenic nature.

We need to allow the biology of the disease in the patient to help define which combination of targeted agents might work best in particular patient groups. An accelerated translational medicine approach, fuelled by a deeper understanding of biology, will undoubtedly provide a clearer and more efficient drug development process, allowing early rejection of less active agents and refining the pathway for delivery of the "right" drug into the clinic. Decreased failure rates will also reduce the economic burden and lead to a more streamlined "discovery to delivery" process.

Raising the Bar; Transforming Patients' Lives

As we develop new and more effective models of drug discovery and delivery, it is also incumbent on both academia and industry to change our mind-set in relation to what we want to achieve. Do we really want to continue our current strategy of small incremental improvements? Should we not be actively pursuing the development of new drug options and combinations that make significant differences to patients' lives? We can no longer afford to pay for drugs that offer only marginal benefit; we need drugs that transform the health of people. While drug development is complex and difficult, we need to raise the bar, break the innovation threshold and focus on a new type of innovation that significantly increases the health of our patients, while contributing to the wealth of our society.


1. Lakdawalla DN, Sun EC, Jena AB et al. An economic evaluation of the war on cancer. J Health Econ 2010;29:333-346.

2. Goldman D, Lakdawalla D, Philipson T. The economic value of medical innovation. Presented at "A Celebration of Science", Washington DC, September 2012.

3. Berrino F, Verdecchia A, Lutz JM et al; EUROCARE Working Group. Comparative cancer survival information in Europe. Eur J Cancer. 2009;45:901-908.

Correspondence: William Hait, M.D., Ph.D., Janssen, The Pharmaceutical Companies of Johnson and Johnson, Route 202 South, Raritan, NJ 08869, USA. Phone: 1-908-927-3516; Fax: 1-908-927-7716; E-mail: Received October 11, 2012; accepted for publication October 11, 2012. ©AlphaMed Press 1083-7159/2012/$20.00/0