By Alexander J. Varond –
On September 25, 2012, the President’s Council of Advisors on Science and Technology (“PCAST”) released a report entitled “Report to the President on Propelling Innovation in Drug Discovery, Development, and Evaluation.” PCAST is a commission of leading scientists and engineers who directly advise the President and make policy recommendations on matters of science and technology. Its most recent report aims at doubling the number of new drugs approved annually, while increasing drug safety over the next 10-15 years.
HP&M’s own Frank Sasinowski was recognized as a key contributor at PCAST’s release of this major new report this week and is cited as a PCAST Drug Innovation Invited Expert on page xvii of the report.
The President personally asked PCAST to investigate and report on ways to propel this kind of innovation in this country for two reasons: first, to better address the suffering of Americans in need of healing therapies; and second, to increase America’s competitiveness in that both we have a positive trade balance in pharmaceuticals and also, research on new medicines is a prime source of jobs here in our pharmaceutical industry and in universities across America. (Note: The President’s only other personal charge to PCAST was on the avian flu crises early in his Administration.)
PCAST engaged a wide range of stakeholders over the past 12 months to identify reasons why the pace of new therapeutic development has not kept up with the huge growth in scientific knowledge, despite substantial increases in R&D budgets. The report set a somber background by explaining that ninety-six percent of orphan diseases lack effective therapies, the costs of illness in the aging US population will reach staggering amounts (e.g., Alzheimer’s disease may eventually exceed $1 trillion per year in the absence of new therapies), the innovative ecosystem for public health is under significant stress, and R&D productivity is substantially declining.
Two key challenges affecting the ecosystem for innovative medicines are:
1. How to accelerate the translation of biological insights into new medicines, including predicting the efficacy and toxicity of candidate drugs to more rapidly identify drugs that are not viable and validating human proteins as “druggable” targets to accelerate development of candidate medicines; and
2. How to address inefficiencies in clinical trials since most clinical trials are currently organized de novo, each time incurring substantial costs that could be reduced by creating efficient trial networks and trial designs.
The report also identifies areas where economic incentives for certain areas of drug development may be insufficient to promote efficient investment in innovation (e.g., antibiotics and complex diseases). It offers suggestions such as developing tools to create incentives such as vouchers for priority review, new exclusivity periods, and targeted tax credits.
Eight specific recommendations were made:
1. Support federal initiatives to accelerate therapeutic development such as the National Center for Advancing Translational Sciences and the Reagan-Udall Foundation.
2. Catalyze the creation of broad-based partnership to accelerate therapeutics by filling key knowledge gaps in drug discovery and development, improving clinical trial capabilities, and clarifying the development pathway for innovative medicines by gathering community input on FDA guidance documents.
3. Expand the use of FDA’s existing authorities for accelerated approval while more fully enforcing requirements for post-approval confirmatory studies.
4. Create a new, optional pathway for initial approval of drugs shown to be safe and effective in a specific subgroup of patients (e.g., FDA could allow the approval a drug for patients with morbid obesity while taking steps to minimize the likelihood that the drug is prescribed off-label to mildly obese patients). This pathway would allow drug sponsors to seek indications for narrow “Special Medical Use” populations which would strongly signal to prescribers and payors that the population that should be prescribed the drug is limited.
5. Explore approaches for adaptive approval via pilot projects under existing pathways to generate evidence across the life-cycle of a drug from pre-marketing through the post-marketing phase. However, PCAST recommends against prematurely creating these pathways through legislation.
6. Improve FDA’s tools for monitoring and communication of clinical benefits and risks, including post-marketing surveillance and FDA’s Sentinel System.
7. Reform management practices at FDA including adding the use of pre-market review leaders to oversee each drug candidate application from its investigational stage through final marketing decision.
8. Study current and potential economic incentives to promote innovation in drug development.
While the advisory report outlines a number of ambitious goals for the drug discovery and development ecosystem, it gave few details of what new laws or regulations might be implemented. For that, we must wait and see on how key stakeholders respond, that is, FDA, industry, academia, the investment community, and patient organizations.