Disruptive Innovation at the NIH. Kathy Hudson, Ph.D. Deputy Director Science, Outreach, and Policy National Institutes of Health

Transcription

1 Disruptive Innovation at the NIH Kathy Hudson, Ph.D. Deputy Director Science, Outreach, and Policy National Institutes of Health

2 NIH: Steward of Medical and Behavioral Research for the Nation Science in pursuit of fundamental knowledge about the nature and behavior of living systems... and the application of that knowledge to extend healthy life and reduce the burdens of illness and disability.

3 NIH FY 2012 President s Budget Request $31,987 Million Increase of $ 745 M or 2.4% over FY 2010 Actuals $40 $35 $30? $25 $20 $15 $10 $5 $ ARRA Program Level CR 2012 PB Note: ARRA funds were appropriated in FY 2009

4 Managing in Uncertain Times Operating at FY 2010 levels for 5+ months Threat of reduction to 2008 levels or worse Many new members are unfamiliar with biomedical research Threat of government shut down when current CR expires Planning for flat budgets

5 House-passed HR 1 Reduce NIH funding by $1.63 billion (-5.2%) below the FY 2010 level -$639.5 million in pro rata reduction across all NIH ICs -$260 million (-2%) reduction to existing non-competing continuation awards for Research Project Grants, eliminating inflation costs Directive to support a minimum of 9,000 new and competing RPGs Mandated cap of $400,000 on average grant size -$48.5 million (-8.9%) for the NIH Common Fund, reducing it to the FY2008 level.

6 Cutting the deficit by gutting our investments in innovation and education is like lightening an overloaded airplane by removing its engine. It may make you feel like you're flying high at first, but it won't take long before you feel the impact. President Barack Obama, 2011 State of the Union

7 NIH Investments in Innovation FY 2012 Advancing Translational Sciences Accelerating Discovery Through Technology Enhancing the Evidence Base for Health-Care Decisions Encouraging New Investigators and New Ideas

8 Therapeutics Development at NIH A 2010 trans-nih inventory of activities relevant to therapeutics development found: Substantial investments in therapeutics development research Approximately 65% for preclinical research; 35% clinical research 550 activities reported of varying sizes and areas of emphasis Drugs Distribution of Investment

9 RESULTS We found that during the past 40 years, 153 new FDA-approved drugs, vaccines, or new indications for existing drugs were discovered through research carried out in PSRIs. PSRI-discovered drugs are expected to have a disproportionately large therapeutic effect.

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11 Valley of Death

12 New Medicines in your Medicine Cabinet: New Molecular Entities Entering Marketplace Source: FDA

13 Most Candidate Compounds Ultimately Prove Ineffective - Pharmaceutical Research and Manufacturers of America; FDA

14 Disease Target ID Assay Dev. HTS Probe to Lead FDA Review Pre- Clinical FDA IND Ph. I Ph. II Ph. III PGx Ph. IV

15 Scientific Management Review Board (SMRB) Recommendations to NIH May 2010 SMRB asked to determine how NIH could better support translational and therapeutic sciences. December 2010 SMRB recommends (12 to 1) that a new translational medicine and therapeutics center be created. SMRB also recommends NIH undertake a more extensive and detailed analysis through a transparent process to evaluate the new center s impact.

16 Creation of the National Center for Advancing Translational Sciences (NCATS) To advance the discipline of translational science and catalyze the development and testing of novel diagnostics and therapeutics across a wide range of human diseases and conditions

17 NCATS: Challenges and Opportunities Deluge of new discoveries of potential targets Unmet therapeutic needs for many conditions, especially rare and neglected diseases Need to view drug development pipeline as a scientific Need to view drug development pipeline as a scientific problem ripe for experimentation and process engineering

18 NCATS: Functions To improve the processes in the therapeutics development pipeline by: Experimenting with innovative approaches along the pipeline through an open-access model Choosing compelling therapeutic projects that can serve to evaluate those novel methods as they move through the pipeline Promoting and facilitating interactions with regulatory agencies to advance the field of regulatory science

19 NCATS: Functions To catalyze the development of novel diagnostics and therapeutics by: Facilitating and supporting partnerships and collaborations across all sectors Providing resources to enhance and enable the development of therapeutics Enhancing training in disciplines that are relevant to translational sciences

20 Disease Target ID Assay Dev. HTS Probe to Lead FDA Review Pre- Clinical FDA IND Ph. I Ph. II Ph. III PGx Ph. IV

21 Quantitative High Throughput Screening Constriction point: traditional HTS at a single concentration High false-positive hit rate requires extensive confirmatory screening Many false negatives result in missed opportunities Process engineering Seven concentrations of each compound screened Decreases time to medicinal chemistry by 6 months Next step Promote adoption

22 Disease Target ID Assay Dev. HTS Probe to Lead FDA Review Pre- Clinical FDA IND Ph. I Ph. II Ph. III PGx Ph. IV

23 Pre-Clinical Toxicity Testing Constriction point: low concordance between animal and human toxicity Skin Cardiovascular Endocrine GI Hematopoietic Hepatic Neurological Urinary Other % of compounds judged safe in animals that are non-toxic in humans Nature Reviews Drug Discovery 3, , 2004

24 Towards Predictive Toxicology Process engineering Current investments High-throughput assays and tests in lower animal species High-throughput whole genome analytical methods on cellbased systems Proposed investments ips technology as in vitro models of human organ systems Retrospective analyses of trial data to develop prospective risk assessors

25 NCATS will: Facilitate not duplicate the translational research activities supported and conducted by the ICs

26 NIH Institutes and Centers NCI NHLBI NIAID OD NIDCR NEI NIA NLM CC NIDDK NIAMS NIDA FIC CIT NHGRI NICHD NCATS NIEHS NIBIB CSR NIAAA NIDCD NINDS NIMH NCCAM NINR NIGMS NIMHD

27 Catalyzing Collaborations Within NIH NCI NHLBI NIAID OD NIDCR NEI NIA NLM CC NIDDK NIAMS NIDA FIC CIT NHGRI NICHD NCATS NIEHS NIBIB CSR NIAAA NIDCD NINDS NIMH NCCAM NINR NIGMS NIMHD

28 NCATS will: Facilitate not duplicate the translational research activities supported and conducted by the ICs Complement not compete with the private sector

29 Catalyzing Collaborations With External Partners Academia Biotech Advocacy Groups NIH Translational Sciences Pharma Non- Profits FDA

30 NCATS will: Facilitate not duplicate the translational research activities supported and conducted by the ICs Complement not compete with the private sector Reinforce not reduce NIH s commitment to basic Reinforce not reduce NIH s commitment to basic science research

31 NCATS Research Programs Components of Molecular Libraries Program Therapeutics for Rare and Neglected Diseases Office of Rare Diseases Research Rapid Access to Interventional Development Clinical and Translational Science Awards FDA-NIH Regulatory Science Cures Acceleration Network

32 NIH Therapeutics for Rare and Neglected Diseases (TRND) Program Congressionally-mandated effort to speed development of new drugs for rare and neglected diseases Collaboration between NIH-intramural and extramural labs with appropriate expertise Projects will: Enter TRND at a variety of stages of development Be taken to phase needed for external organization to adopt for clinical development Not duplicate pharma projects TRND will encourage creative partnerships; novel approaches to intellectual property

33 TRND Pilot Projects Disease Type Pathology Collaborators Compound type Stage Niemann-Pick Type C Rare CNS, liver/spleen Disease Fnd, Extramural, Intramural Repurposed approved drug Preclinical Sickle Cell Disease Rare Blood Biotech, Intramural NME IND-enabling studies & clinical trials design Chronic Lymphocytic Leukemia Rare Cancer Disease Fnd, Extramural Repurposed approved drug Pre-IND Hereditary Inclusion Body Myopathy Rare Muscle Biotech, Intramural Intermediate replacement IND-enabling studies Schistosomiasis, Hookworm Neglected Infectious parasite Extramural NME Lead optimization

34 Disease Target ID Assay Dev. HTS Probe to Lead FDA Review Pre- Clinical FDA IND Ph. I Ph. II Ph. III PGx Ph. IV

35 NCATS Research Programs Components of Molecular Libraries Program Therapeutics for Rare and Neglected Diseases Office of Rare Diseases Research Rapid Access to Interventional Development Clinical and Translational Science Awards FDA-NIH Regulatory Science Cures Acceleration Network

36 Clinical and Translational Science Awards 55 CTSA sites in 29 states

37 NCATS Research Programs Components of Molecular Libraries Program Therapeutics for Rare and Neglected Diseases Office of Rare Diseases Research Rapid Access to Interventional Development Clinical and Translational Science Awards FDA-NIH Regulatory Science Cures Acceleration Network

38 Cures Acceleration Network (CAN) Established by the Affordable Care Act CAN will Advance the development of high need cures Reduce barriers between research discovery and clinical trials in areas that the private sector is unlikely to pursue in an adequate or timely way Review Board advises NIH Director 24 members, including representatives from academia, private industry, and patient advocacy groups

39 Cures Acceleration Network: Funding Mechanisms Grant Awards: Up to $15 million per award per fiscal year Partnership Awards: $1 match for every $3 from NIH Up to $15 million per award per fiscal Flexible Research Awards: DARPA-like authority Not to exceed 20% of total appropriated funds in any fiscal year

40 To win the future, America needs to out-educate, outinnovate, and out-build the rest of the world. President Barack Obama, Weekly Address February 5, 2011

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