President’s Council of Advisors on Science and Technology: Propelling Innovation in Drug Discovery, Development, and Evaluation

Due to biomedical innovations—including advances in medicines, medical procedures, and public health, life expectancy at birth has risen from around 47 years at the turn of the 20th century to 78 years today, and many diseases that were once fatal or debilitating can now be prevented, delayed, or ameliorated.   

In fact, pharmaceutical therapies have helped lead to vaccines that have eradicated or controlled many devastating infectious diseases including polio, small pox, and measles.  HIV is now treated with over 20 Food and Drug Administration (FDA)-approved drugs.  Multi-drug regimens effectively control HIV infection, preventing the development of AIDS.  Pharmaceutical therapies have led to cures for multiple malignancies that were once universally fatal; for example, childhood leukemia is now cured in 80 percent of cases, testicular cancer in over 90 percent of cases, and Hodgkin’s lymphoma in over 90 percent of cases.  Along with a reduction in smoking and better medical care, cholesterol-lowering therapy, blood-pressure-lowering drugs, anti-platelet agents, and diabetes treatment have contributed to a substantial decrease in death from heart attacks (70 percent decline over the past 60 years). 

A recent report recognized that in addition to academic researchers who “have unlocked secrets of basic biology and revealed mechanisms that underlie disease,” these innovations have been brought forth by a “a robust bio-pharmaceutical industry, which has developed molecules to treat disease and conducted clinical trials to demonstrate their efficacy.”  Despite this progress, challenges remain.   

To address these challenges, “The United States should set a goal of doubling the output of innovative new medicines that meet critical public health needs over the next 10 to 15 years, while continuing to increase drug safety,” a presidentially appointed council of experts advised in a report released in late September.  The council recommends a number of actions involving industry, academia, and the Federal Government.  

“While basic biomedical sciences have seen stunning progress in past decades, challenges remain in translating those scientific advances into practical solutions,” according to the report—Propelling Innovation in Drug Discovery, Development, and Evaluation—produced by the President’s Council of Advisors on Science and Technology (PCAST).  The report assesses the reasons for that long-term trend.  

To support innovation and accelerate the development of new therapies, the report makes a number of detailed recommendations aimed at  

• bolstering the discovery and development of new therapeutic compounds;
• optimizing processes used by the Food and Drug Administration (FDA) to evaluate the safety and efficacy of candidate drugs;
• enhancing long-term monitoring of approved medicines; and
• enhancing public understanding about the benefits and risks of medicines.  

“With improved collaboration among all the participants in the drug development ecosystem and optimization of drug-evaluation pathways, American researchers and companies should be able to accelerate the development of safe and effective drugs while also strengthening the U.S. economy,” said Eric Lander, who co-chairs PCAST.  

The report notes that heart disease and stroke remain leading causes of mortality, many common cancers are still incurable unless they are caught in the earliest stages, and the vast majority of rare diseases lack effective therapies altogether.  Infectious diseases, including those caused by antibiotic-resistant bacteria and viruses with pandemic potential, pose a constant threat of large-scale mortality. And treatments for psychiatric diseases, which impose a tremendous burden on society, are frustratingly limited in their efficacy, as are treatments for neurodegenerative diseases such as Alzheimer’s.  

All three major components of the drug development ecosystem—basic biomedical research in universities and research institutes, clinical research in hospitals, and drug discovery and development in the biopharmaceutical industry—are facing growing challenges as the time, complexity, and cost of developing drugs have gone up, the report states.  The rate of new-drug applications submitted by industry to the FDA, as well as new drug approvals, has remained relatively constant for 20 years.  In an encouraging sign, however, the FDA approved 35 new medicines in the past year—among the highest totals in the past decade. 

The report concludes there are two critical needs related to drug discovery and development that must be addressed to advance innovation:  

(1)  Scientists need better methodologies and tools for translating basic biological insights into validated therapeutic targets and leads—a gap in the drug discovery and development pipeline that academic scientists often view as “too applied” and pharmaceutical companies often eschew as “too basic” to justify private investment.  

(2) Pharmaceutical developers and regulators need to incorporate new efficiencies into clinical trials of candidate medicines—complex and costly human studies that today constitute fully 40 percent of the biopharmaceutical industry’s R&D budget.  

To achieve some of the report’s broader goals, PCAST recommends the creation of a public-private “Partnership to Accelerate Therapeutics,” involving representatives from the bio-pharmaceutical industry; the academic biomedical research and ethics community; physician societies and pharmacists; patient-focused research foundations and advocacy groups; healthcare providers and insurers; and the Federal Government. The Partnership would help identify and plan collaborative actions to speed drug development while balancing competing stakeholder interests and minimizing duplication of efforts.  

This report should be applauded for such a recommendation.  We have long praised industry collaboration, and with such a large and diverse group of stakeholders, we are hopeful that this report will lead to more progress and innovation.  The report recognized that “development of innovative medicines … remains essential for progress in the prevention and treatment of human disease.” 

In addition, the report concludes that the return on investment in certain disease domains may be too low to justify their pursuit by companies, even though the potential benefits for public health in these domains may be large.  It recommends that the Department of Health and Human Services (HHS) commission a study to assess potential mechanisms to encourage companies to tackle important medical challenges that may be financially unattractive.  

“There is a tremendous need for new antibiotics, for example, but the potential market share for such medicines is typically small and their duration of use is typically short,” said PCAST member Christine Cassel, a physician who—with Lander and PCAST members Ed Penhoet and Rick Levin—oversaw a group of 30 outside experts who helped inform PCAST in its work.

R&D Under Stress

The report recognized, contrary to some critics assertions, that there is evidence that industry R&D investment, a major component of this innovation ecosystem, is under significant stress: 

• The pharmaceutical industry is facing the largest “patent cliff” in its history: drugs with annual sales exceeding $200 billion will come off patent in the period 2010-2014, resulting in a loss of more than $100 billion in sales to generic substitutions; only a small fraction is expected to be replaced by new product revenues.
• Venture capital to start new biotechnology firms and fund innovative drug development activities appears to be declining, due not only to general economic conditions but to what are cited as concerns about unfavorable returns in the drug-innovation sector.
• Many companies are exiting important fields of critical public health need. For example, despite the growing health care and economic burden of neurodegenerative diseases, such as Alzheimer’s disease and psychiatric diseases, many major pharmaceutical companies are closing down or severely curtailing drug discovery programs. 

The report identified two critical areas related to drug discovery and development that must be addressed to advance innovation: 

1. 1.    Scientific knowledge gaps between basic research and commercial projects.
2. 2.    Inefficiency in clinical trials.  

The report also highlighted multiple issues and opportunities that relate to the evaluation of new drugs for approval:   

1. There are opportunities to accelerate the approval of a broader range of truly innovative drugs for patients who need them. Such acceleration should be supported by stronger tools for and enforcement of post-approval study 
2. The FDA requires methods to rapidly approve drugs for narrow populations for which there is a favorable benefit-risk balance, while protecting the broader population from drugs that have an unknown or unfavorable benefit-risk balance 
3. Stronger post-marketing surveillance and communication tools are needed to generate evidence on the benefits and risks of drugs and to communicate those benefits and risks to the public 
4. Innovators require greater clarity about general regulatory pathways for innovative products and approaches 
5. Innovators require greater consistency, efficiency, and communication with respect to their individual drug applications 

These recommendations are encouraging.  We have seen the pharmaceutical and medical device industry significantly maligned for their attempts to create wealth from medical products.  Reports like these go a long way to dispelling the myth that creating new products is easy and can cost as little as a million dollars.  The truth drug development is around $3 billion per new product which in the end may not be sustainable.  A little encouragement from the Whitehouse on the need for reduced regulations will go a long way to encouraging future investment.