Pharmaceutical development and discovery has faced significant challenges over the past several years. While the rate at which new molecular entities have been approved has remained essentially constant since 1950, “the declining rate of new-drug approvals suggests that the current approach to drug development is unsustainable.” What makes the past approach even more problematic is that the current regulatory and political environment has placed tremendous pressure on companies to reduce the pricing of patented drugs.
One way to address these challenges, according to a recent article in the Mount Sinai Journal of Medicine, is to create a more “modular approach to drug discovery and development,” which should derive some of its features from the not-for-profit sector. As the author, Garret A. Fitzgerald proposed, “we must address the deficit in human capital with expertise in both translational medicine and therapeutics and also in regulatory science.” Interestingly, while most successful innovations follow bottom up pathways, Dr. Fitzgerald argues for a more sensible top-down approach. He also recognized the need to:
– Utilize regulatory reform to incentivize innovation and the expansion of the precompetitive space; and
– Develop an informatics infrastructure that permits the global, secure, and compliant sharing of heterogeneous data across academic and industry sectors.
In proposing a strategy to meet these needs, Dr. Fitzgerald acknowledged that “these developments, likely prompted by the perception of crisis rather than opportunity, will require linked initiatives among academia, the pharmaceutical industry, the National Institutes of Health (NIH), and the Food and Drug Administration (FDA), along with a more adventurous role for venture capital.” He asserted that without this collaboration, the United States’ lead in biomedical science and in the development and regulation of novel therapeutics will be threatened.
Consequently, drug development for the most part has remained unreformed. The actions that pharmaceutical companies have taken to address the dramatic decline in the growth of prescription-drug sales in the United States, such as mergers, “have failed to foster innovation, sustain creativity, and accelerate the delivery of new drugs.” And programs in the U.S. which are being started now to research comparative-effectiveness, similar to the success of the National Institute for Health and Clinical Excellence (NICE) in the United Kingdom, will only further depress U.S. drug pricing.
As a result of the pressure these activities place on drug pricing, Dr. Fitzgerald asked how industry, academia, and the FDA might position themselves to anticipate such transition to a more global, less-integrated, and modular approach to drug discovery and development.
First, he recognized the need to “bridge the deficit gap in human capital,” since “the number of people who can project basic science across the translational divide into mechanistic studies of drug action in humans has declined alarmingly in industry, academia, and the FDA.”
Dr. Fitzgerald maintained that although “it is the responsibility of academia to provide such interdisciplinary training to address this alarming decline, the experience should include exposure to drug development in a commercial setting and to the demands and process of regulatory science.” He noted how some initiatives are already underway that address this gap in manpower, such as the ‘Wellcome Trust, which has funded 4 centers of excellence in translational medicine and therapeutics focused on training.
Each academic center has an industrial partner that contributes “expertise to the teaching program and an environment where trainees can be exposed to drug development in the setting of a for-profit company.” In light of the current regulatory and economic environment these kinds of partnerships are very promising to help translating research into products people can use and benefit from.
In the U.S., the consortium of the National Institutes of Health (NIFI) Clinical and Translational Science Awardees (CTSA) has also launched initiatives to foster interaction among the academic sector, industry, and the FDA focused on improving the efficiency of the development of novel therapeutics. To continue accomplishing this kind of program, Dr. Fitzgerald recognized the need for “a common nomenclature by the stakeholders, the funding of training programs, and the evolution of career structures.”
While some may perceive this approach as turning universities into drug companies, Dr. Fitzgerald explained that the goal of industry-academia collaboration “is to increase the number of translational scientists who can pursue research between point of conception (POC) in cells and model systems and the study of mechanism-physiology, disease, and drug action in humans.” He recognized that while “some of these individuals will remain in academia there is a need for such interdisciplinary expertise in Pharma, biotech, venture industries, and the FDA.”
In addition to these partnerships, Dr. Fitzgerald acknowledged the need to harness and integrate the best experts in the world at the various stages of drug discovery and development, and “bring their information on to a secure, compliant, globally accessible informatics infrastructure that is sufficiently flexible to permit access by industry, academic, and regulatory partners.”
Although large Pharma already communicates such information intramurally to some degree, “academic investment has lagged and been uncoordinated, even within institutions.” Often, the funding systems are insufficient for academic institutions, which is why combining industry and academia might effectively resolve such issues.
In fact, collaborating with industry offers a number of ways to resolve issues because through the creation of a sufficient fund, leading academic groups are engaged to “interact with industrial partners, relax or postpone their claims of IP, hand off data sets in a timely fashion, and share academic credit.” Impressive examples of success stories for such interactions include Medicines for Malaria Venture, the TB Alliance, and the Institute for OneWorld Health.
Dr. Fitzgerald also mentions using “prizes or funds to foster innovation and discovery,” an approach that “has been used quite broadly across industries.” He explained that “such incentives have been launched in many countries and in targeted areas, such as genomics, to hasten the personalization of medicine.”
Another opportunity for academia to work with industry is to address the lack of capacity academia has to “perform the medicinal chemistry to harvest the potential therapeutic benefit of its biological discoveries. Few US academic departments of chemistry are incented to fulfill this goal.” As a result, Dr. FitzGerlad notes that this gap poses a great “opportunity to interact with Pharma or with academic chemistry departments in countries where cost structures are lower and expectations of chemistry departments are different from those in the United States and other developed countries.”
He also recognized “the lack of funding available within academia to pursue the development of a therapeutic.” Dr. Fitzgerald explained that “NIH funding structures are not suited to support the necessary replication of POC studies, pharmacokinetics studies and modeling, the extramural toxicology screens, and the requisite medicinal chemistry and scaling required of such an endeavor.” To address this issue of funding, partnering with industry offers tremendous promise. In fact, “an interesting initiative in the private sector is already underway involving “the co-development with academic investigators of an early lead with the first option of buyback at a later, more advanced stage of development.”
Conclusion
There are a number of factors affecting drug development presently, and while parts of it are “undergoing a process of modest and gradual reform, rapidly evolving economic and political pressures may converge to prompt a much more disruptive initiative,” as was seen by many executives in the publishing, airline, music, and financial-services industries.
As a result, to prevent this disruption Dr. Fitzgerald asserts that “the academic sector needs to be empowered if it is to contribute more substantially to drug and device development.” To do so, we need more collaboration between industry-and academia because otherwise, the United States’ will lose its lead in biomedical science and in the development and regulation of novel therapeutics.