CPTR 2013 Workshop September 30 th - October 3 rd. CPTR Roadmap: Accomplishments and Future Direction

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1 CPTR 2013 Workshop September 30 th - October 3 rd CPTR Roadmap: Accomplishments and Future Direction

2 CPTR Mission & Purpose Accelerate the development of new, safe, and highly effective regimens for TB by enabling early testing of drug combinations.

3 First New Treatment in Decades SIRTURO : FDA accelerated approval Dec 28, 2012 Janssen Pharmaceuticals, Inc. 2012

4 Novel Regimens in Development PA Moxifloxacin + Pyrazinimide (PaMZ) PaMZ is being investigated in both TB and MDR-TB patients in the 8-week study NC-002. It successfully completed a two-week clinical study (NC-001) in Most advanced novel regimen in global pipeline NC-003: PA Moxifloxacin Multiple-arm + trial Pyrazinimide testing new regimens (PaMZ) NC-003 is a multiple-arm study testing additional new TB regimens with the potential to even further shorten treatment for TB and MDR-TB. TB Alliance Overview 4

5 The Challenge Continues Need emphasis on combination study approaches with multiple novel entities rather than development of single agents Increasingly fragile TB drug development pipeline with the continued divestment of companies in the antiinfective space Public health crisis looming and TB is the case study for consequences of inaction

6 The Opportunity Has Expanded Accelerate the development of a regulatory approvable in vitro diagnostic assay for rapid drug susceptibility testing of TB to facilitate drug development and rational use of new drug regimens. In partnership with NIAID

7 CPTR Expanded Structure Regulatory Science Consortium Research Resources Group Rapid DST Consortium Drug Development Coalition In partnership with NIAID

8 CPTR Working Group Structure Regulatory Science Consortium Rapid DST Consortium Research Resources Group Data Standards & Integration WG Biomarkers & Clinical Endpoints WG Preclinical & Clinical Sciences WG Modeling and Simulation Health Authorities Submission WG Enabling Sciences WG Assay Development WG Surveillance Drug Development WG Coalition Economic Assessment & Impact Modeling WG Clinical Trials Infrastructure WG Global Regulatory Pathways WG Stakeholder & Community Engagement WG Access & Appropriate Use WG [Enter Presentation Title in Insert Tab > Header & Footer 8

9 Regulatory Science Consortium Regulatory Science Consortium Research Resources Group Role in Enabling & Accelerating the Process: Drug Development Coalition Identify tools/methods that can bring the most value Reach scientific consensus by sharing expertise, information, data Collaborate with regulators on DDT development & use Proceed with regulatory qualification when appropriate 9

10 Key Accomplishments-Reg Sci WG s TB Data Standards and Integration TB Data Standard Version 1.0 launched an available for use on CDISC site TB data repository developed and launched for remapping of key data sets to the new standard Biomarkers and Clinical Endpoints Official FDA Response to Letter of Intent July 2013 Analysis plan developed by team to be sent for review via Pre-IND mechanism EMA submission pending Pre-Clinical and Clinical Sciences Planned Voluntary Exploratory Data Submission meeting with FDA; Briefing book submitted LOI and Briefing book to be submitted simultaneously to EMA Modeling and Simulation Existing TB progression models evaluated LAP&P SIMCYP platform PBPK module complete Proposed expansion 10

11 Modeling and Simulation WG Potential Expansion Vision: More efficient translation between each stage of drug development Systems Biology Model Continuously revise and refine with relevant data (summary and subject-level) Network Biology Right Pathway Pharmacology Right Target Preclinical PKPD Right Molecule Clinical Pharmacology Right Dose Pharmacometrics Right Patients Pathway Target Drug Disease Hollow fiber model Physiologicallybased PK models Clinical trial simulation tools (drug-disease-trial models) 11

12 Research Resources Arm Regulatory Science Consortium Research Resources Group Role in Enabling & Accelerating the Process: Identify regulatory Rapid DST challenges and influence for Drug more Development efficient regulatory pathways Consortium Coalition Ensure effective collaboration of key stakeholders for TV regimen development and develop resources to facilitate community engagement within TB drug and regimen trials Develop robust inventory of clinical trial infrastructure to aid in TB drug and regimen trials

13 Key Accomplishments Global Regulatory Pathways Pre-workshop satellite meeting to facilitate dialogue between national regulatory authorities, FDA, EMA and WHO FDA & EMA presented recent developments in thinking regarding TB regimen development; WHO Pre-Qualification process; presentation of challenges from high burden countries- outputs will guide 2013 strategy Stakeholder & Community Eng. Manuscript published Engaging communities in Tuberculosis research (Lancet) building on the release of Good participatory Practice Guidelines for TB Drug Trials Will seek to develop tools and training resources to facilitate use of CPP-TB and other CE resources 13

14 Rapid DST Consortium Role in Enabling & Accelerating the Process: Support the development of iterative TPP s Facilitate development of rapid DST assays that could be commercialized Increase understanding of resistance trends to support rapid DST development Develop models that inform TPP s and policies for use of DST Reach scientific consensus by sharing expertise, information, data Rapid DST Consortium Drug Development Coalition 14

15 Future Pipeline Existing Rapid DST TPPs Will Be Iterative 1 st line regimens 2 nd line regimens ReMOX launch? PaMZ PhIII clinical trial PaMZ launch? New regimen PhIII clinical trials New regimen PhIII clinical trials DST Consortium DST Consortium DST Consortium DST Consortium Development/Clinical Trials/WHO Endorsement/ Health Authority Approval 10/31/2013 Round 1 DST TPP for Industry (-PZA?) 3/31/2013 Round 2 TPP for Industry (+PZA?) November 2014 Round 2 TPP for Industry (+PZA?) 3/30/2015 Alere Case Detection Test 6/30/2015 Alere Drug Resistance Test July 4, 2013 January 2, 2016 BMGF 15

16 Rapid DST Consortium WG s Work Group Focus and Purpose Enabling Science WG Facilitate developing Rapid TB DST assays to meet target product profiles & coordinating with industry to develop commercial in vitro diagnostic assays for TB DST, meeting target product profiles. Assay Development WG Focus on the discovery and validation of the molecular basis for resistance and correlation of resistance with clinical outcome. Surveillance WG Economic Assessment/ Impact Modeling WG Increase understanding of the magnitude of drug resistance and trends for resistance in high burden countries and the global geography of drug resistance to inform clinical trial planning and clinical practice. Development of more cost effective strategies for surveillance of TB drug resistance. Develop models that will inform decisions needed to develop target product profiles and to inform policy about use of DST with anticipated TB drug regimens.

17 Collaborators- Thank you Members