The 2008 global financial crisis and an impending “patent cliff” have had a profound impact on the profitability of the pharmaceutical industry – they have made it change how it works. So, to maintain dynamism and profitability, the pharmaceutical industry is now fostering a new paradigm in drug development.
The financial breakdown reduced the availability of “high-risk, high-return” venture capital that has traditionally supported the early stages of drug discovery and development by funding high-risk biotechnology companies.
And the large number of multi-billion dollar drugs which are reaching the end of their patent-protection means that the industry is facing a “patent cliff”. Once drugs come off patent, they are susceptible to competition from generic equivalents, which quickly erode profits. Many of the most profitable drugs have been around for a long time because new blockbuster drugs need to show better outcomes for patients.
To maintain their profitability, the industry is trying to create a pipeline of high-value products through mergers among big companies and acquisition of smaller, specialised biotechs with products in advanced stages of clinical development. But there’s a limited number of “advanced” drug development programs where clinical demonstration of efficacy seems unequivocal. And this means that the industry must innovate new ways to develop products.
Traditional industry drug discovery
Early drug discovery involved testing selected drug candidates using small groups of animals in place of human patients. The type of animal selected would predict human response to the drug. Scientists would build on their historical knowledge of the animals’ drug response to tweak the drug’s properties and achieve the desired clinical effect. Drug discovery was, in effect, an art.
Advances in the study of genes and the proteins they encode have provided a more fundamental understanding of how diseases work. This has led to a reductionist approach to drug discovery; the industry anticipated that the process of drug discovery might be automated and reduced the need for art.
Animal testing started to be preceded with much simpler tests of drug efficacy, and drug development was transformed with this production-line mentality. Technological advances meant that hundreds of thousands of candidate drugs could be prepared, and millions of tests could be applied to select the “right drug” for further development.
Unfortunately, living organisms and their responses to drugs have proven to be much more complex than is provided for by such a simplistic approach. And the low success rate of this strategy has contributed to the decline in the pipeline of drugs.
Traditional academic drug discovery
New ways to treat disease have typically drawn on discoveries made by university-based researchers. In the traditional model, academia was relied on to do fundamental research into the nature of diseases. Better understanding of the root cause of a disease would often lead to identifying new ways to treat it.
In cases where a new drug was discovered, the intellectual property was typically spun out of academia, into a nascent biotech company. Such companies would then raise funds from investors who were tolerant of risk. The company would then undertake early stage clinical trials to demonstrate that the new treatment provided improved patient outcomes. Investor risk was justified by returns on investment that were at least tenfold the initial sum.
Many more drug candidates enter the rigorous proving ground of clinical development than ever make it to the shelves of a high street pharmacy. Even if a drug passes the many hurdles and reaches Phase 2 clinical development, where it will, for the first time, be administered to patients and volunteers (not healthy ones as in Phase 1), there’s still a high likelihood of failure. The most common causes of failure at this stage are either toxicity, or through a lack of benefit.
The pharmaceutical industry has relied on this biotech model to provide a pipeline of “de-risked” drug candidates. But the evaporation of “high risk” funding since the financial crisis means this traditional biotech model has diminished capacity.
So this model is now being supplemented by a new industry–academia relationship. In the past five years, the pharmaceutical industry has sought to engage with academia much earlier in the process. The aim is to support the discovery and validation of new and improved treatments for diseases such as diabetes, cancer and heart disease, and to work in partnership to bring drug candidates to clinical development.
A catalogue of these relationships has recently been published by Nature:
Pfizer with a consortium of seven institutes in New York for biological drugs;
Sanofi with UCSF for Aging, Diabetes and Inflammation;
Gilead with Yale for Oncology;
GSK with University of Manchester for Inflammation;
Astra Zeneca also with the French National Institute of Health and Medical Research for Cancer, Inflammation, Respiratory and Autoimmune disease, and
Takeda with Kyoto University for Obesity and Schizophrenia.
The long-term basis for these relationships is the recognition by the pharmaceutical industry that a sustainable product pipeline might be achieved by nurturing talented academic partners. On the other side of the equation, academia is aware that getting funding of research is continually becoming more competitive, and an industry partner with deep pockets is an effective way to advance fundamental research as well as facilitate the translation of this research into improved patient care.
The next few years will see a vastly different pharmaceutical industry emerging as it grapples with change, sustainability and, hopefully, an increased ability to meet medical need. This could be the beginning of a beautiful friendship.
What do you think of a closer relationship between academia and the pharmaceutical industry?
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Hear industry experts speak about what lies ahead for the Australian medicines industry in a changing global market at 6 PM today (Wednesday, February 15) at Baker IDI Heart and Diabetes Institute, Level 7, 75 Commercial Road, Melbourne.
RSVP to firstname.lastname@example.org or call (03) 8532 1361.