Next Generation TB Diagnostics


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  • Thank you for this opportunity to talk briefly about our work in TB diagnostics. One caveat – As I am not the Diagnostics PO, so I am here presenting on behalf of others and representing their work. At today’s session I will provide a brief overview of our work, focusing on the Next Generation TB Diagnostics Program and the TB Diagnostics Forum. Note this presentation is largely focused on the foundation’s work, and makes limited reference to a large body of relevant science and R&D done by many other groups. We need to continue broad engagement in this area for the world to make progress.
  • The overall goal of the Gates Foundation TB Strategy is to accelerate the reduction of global TB incidence. Paths to reduce incidence include vaccination with a new, effective vaccine or use of a combination of drugs and diagnostics using a “test and treat” strategy. To approach global goals, models show that a combination of these two approaches will be needed. However, in the near term the probability of success for drugs and diagnostics is significantly higher than that for vaccines. Drug regimens are proceeding with development. REMox will have completed phase 3 studies in 2013 and PaMZ will have completed phase 2b studies in the same year. We are increasingly working to link diagnostic development with the drug pipeline to maximize health impact of new drug regimens and to reduce emergence of resistant disease. As you can see in the diagnostics box, we have set the goal of identifying a new TB biomarker that will enable progress towards a TB point of care diagnostic. We have also set a goal of two new molecular diagnostics for TB, which will result in an increasingly competitive global market for TB diagnostics that are accurate, easy to use, and closer to patients.
  • This slide summarizes significant recent progress in TB diagnostics and the way forward. True point of care diagnostics will all rely on biomarker discovery. In the meantime, we are supporting work to improve molecular diagnostics and drug sensitivity testing, and to bring these technologies as close as possible to the peripheral level.
  • Despite recent advances, microscopy remains the only widely-available test in most settings. In the near-term the world needs to expand access to current and next generation molecular diagnostics. Molecular diagnostics are a bridge to true POC diagnostics. In the more distant future, new biomarkers may enable development of tests that are truly fieldable at the point of care.
  • The field of molecular diagnostics is competitive and dynamic. Four NAAT tests will be introduced in the next six months, two of these are from developers in emerging economies. These will pose challenges for people working in TB control to understand the pros and cons of different tests and how to incorporate them into diagnostic algorithms.
  • We want to move beyond fast followers, supporting next generation molecular diagnostics that can be used at peripheral labs. We decided to get as close as possible to the upper right hand box, which has advantages over existing technology in terms of both cost and accessibility to the patient. Our TPP was focused on identifying that could fit in the upper right hand box. This is will have greater impact than a simple fast follower with characteristics similar to existing technologies.
  • We organized two RFPs one global, one focused on China, to facilitate identification of technologies that would enable this vision.
  • This slide summarizes some of the key characteristics of the target product profile for next generation diagnostics in recent RFPs. We are currently in the process of assessing applications. We expect to make our grant as part of this program in early 2013, with products available by 2015.
  • Caveat – As I am not the Diagnostics PO, I am here presenting on behalf of others and representing their work
  • A number of problems are facing the TB world with continued progress on new drugs and regimens. Given significant levels of drug resistant TB, the world needs to protect new drugs from resistance as much as possible. However, given the historic lack of investment in TB R&D, significant gaps remain in our understanding of key areas, such as the mechanism of action of Pyrazinamide, and consensus on the best methods for drug resistance testing. In addition, addressing the goal of reducing drug resistance will require coordination between different parties that are currently working independently.
  • The TB Diagnostics Forum was established this year to coordinate research and facilitate communication. The Forum has identified rapid DST as an initial topic of focus.
  • The structure of the forum will be established in early 2013, but it is proposed to organize work into four workgroups, with leadership and support that is needed to make progress.
  • This timeline summarizes a coordinated vision for TB diagnostic and drug development in the coming years, with a focus on our work. We need your support to make this happen, and welcome your participation in this work.
  • We are one of several groups, including Grand Challenges Canada, supporting research to identify TB biomarkers. We will rely on this for transformational change in TB diagnostics.
  • Next Generation TB Diagnostics

    1. 1. Next Generation TB Diagnostics –An Update from BMGFLee Pyne-MercierNovember 2012
    2. 2. Presentation Outline  Foundation Strategic Context  Next Generation TB Diagnostics Program  TB Diagnostics ForumDecember 28, 2012 © 2012 Bill & Melinda Gates Foundation | 2
    3. 3. Presentation Outline  Foundation Strategic Context  Next Generation TB Diagnostics Program  TB Diagnostics ForumDecember 28, 2012 © 2012 Bill & Melinda Gates Foundation | 3
    4. 4. TB Strategy 2011-2016: Goal and vision of success the reduction of global TB incidence Impact goal Accelerate Vaccines 1 vaccine candidate in phase 3 Drugs 1 TB drug regimen in phase 3 • 1 new TB biomarker identified Diagnostics • 2 new molecular diagnostics endorsed by WHO STAG Country-level • Increase national TB budgets Innovation in TB • Accelerated uptake of innovative TB control Control • New products with frugal engineeringGlobal Access and • Reduced costs of FDC and second-line drugsMarket Dynamics • Accelerated uptake of innovation in target countries and globally Advocacy Funding secured for one TB vaccine and one TB drug phase 3 clinical trial December 28, 2012 © 2010 Bill & Melinda Gates Foundation | 4
    5. 5. Presentation Outline  Foundation Strategic Context  Next Generation TB Diagnostics Program  TB Diagnostics ForumDecember 28, 2012 © 2012 Bill & Melinda Gates Foundation | 5
    6. 6. Significant Progress To Date in TB Diagnostics; Challenges RemainDecember 28, 2012 © 2012 Bill & Melinda Gates Foundation | 6
    7. 7. December 28, 2012 © 2012 Bill & Melinda Gates Foundation | 7
    8. 8. Fast-follower NAATs are rapidly entering the market Loopamp® by Eiken, Japan TrueLab® by Molbio, India GeneDrive® by Epistem, UK NATeasy® by Ustar, China
    9. 9. Simple and Affordable Molecular Testing for Tuberculosis “To support the creation of a validated, low- cost, nucleic-acid assay for clinical TB detection on platforms capable of operation in rudimentary laboratories in low-resource settings. It is our intention for these assays to be to created and validated for use within 24-36 months”December 28, 2012 © 2012 Bill & Melinda Gates Foundation | 10
    10. 10. Target Product Profile – Key Characteristics Characteristic Optimal Minimal Cost of consumables < $4 < $8 Cost of instrument < $5,000 < $10,000 Time to market < 24 mos < 36 mos Specificity > 99% > 97% Sensitivity > 98% smear-positive and 80% 95% of smear-positive and 65% smear-negative patients smear-negative patients Sample Prep & processing Integrated Minimal, < 5 steps Time to result < 1 hour < 2 hours Sample type Sputum Sputum Drug resistance screening Detection of Rif, FQ, and INH Rifampin drug resistance resistance testing via a testing via a separate cartridge separate cartridge with with additional consumable additional consumable cost cost (Reflex Testing) (Reflex Testing) Training < .5 day < 1 dayFull TPP Available: December 28, 2012 © 2012 Bill & Melinda Gates Foundation | 11
    11. 11. Presentation Outline  Foundation Strategic Context  Next Generation TB Diagnostics Program  TB Diagnostics ForumDecember 28, 2012 © 2012 Bill & Melinda Gates Foundation | 12
    12. 12. Problem Statement  Progress is accelerating on drug regimens (REMox, PaMZ)  Desire to save new drugs from resistance  Historic underinvestment in TB R&D has led to significant unknowns, specifically related to DST for key regimen components  Lack of coordination between researchers, drug developers, and the public health community that will be needed to achieve a common goalDecember 28, 2012 © 2012 Bill & Melinda Gates Foundation | 13
    13. 13. Background and Purpose TB Diagnostics Forum established in 2012 in collaboration with NIH Overall purpose is to facilitate: • Communication and discussion of research priorities, research gap areas, and new relevant data • Coordination of research and research funding • Collaboration on select projects The Diagnostics Forum has identified rapid drug susceptibility testing as an initial topic of focus.
    14. 14. Proposed Structure TB Diagnostics Research Forum Coordinating Committee NIH, CDC, BMGF, WHO, EDCTP Forum Coordinator Enabling Science Modeling Workgroup Surveillance Assay Development Workgroup Chair: David Dowdy Workgroup Workgroup Chair: David (JHU) Chair: Bonnie Chair: Mark Perkins Sherman (Seattle Plikaytis (CDC) (FIND) Biomed) Program Management SupportDecember 28, 2012 © 2012 Bill & Melinda Gates Foundation | 15
    15. 15. Coordinated timeline – BMGF Activities 2012 2013 2014 2015 2016 2017 Drug Development Bedaquiline Delaminid REMox PaMZNext Generation Next Generation Diagnostic DevelopmentTB Diagnostics Next Generation Diagnostic Development Enabling Science for Rapid DST (e.g. PZA)TB Diagnostics Rapid DST Development/Adaptation Forum Enhanced Drug Resistance Surveillance Modeling to Support Rapid DST Project TB Biomarker Phase 1 Program Field Validation of Leads December 28, 2012 © 2012 Bill & Melinda Gates Foundation | 16
    16. 16. Grand Challenge: Biomarkers for the Diagnosis of TB $7.7M invested in 10 projects, 24 month grants Program Goal: support innovative research to facilitate development of a low-cost, simple-to- use tool that can quickly and accurately diagnose TB in developing countries Investigators are evaluating both host and pathogen markers in highly characterized clinical samples through partnership with FIND Concurrent development of TPPs for POC diagnostics to inform decisions December 28, 2012 © 2010 Bill & Melinda Gates Foundation | 17
    17. 17. Thank You© 2012 Bill & Melinda Gates Foundation. All Rights Reserved.Bill & Melinda Gates Foundation is a registered trademark in the United States and other countries.