Although it is often thought of as a disease of the past, 1.7 million people die every year from TB.
Critical Path to TB Drug Regimens (CPTR)
The Critical Path to TB Drug Regimens (CPTR) Initiative is a broad collaboration of pharmaceutical companies; government, regulatory, and multilateral agencies; academia; civil society; advocates; and non-government organizations, that aims to accelerate the development of new, safe, and highly effective tuberculosis (TB) treatment regimens with shorter therapy durations. Although TB is often thought of as a disease of the past, 1.7 million people die from it each year. The drugs are over 40 years old, have significant adverse effects and drug interactions, the treatment regimens are unacceptably long, resistance to current drugs is increasing, and the standard sequential regimen development process would be unacceptably long. The mission of CPTR is therefore to address an urgent global public health need, with the goal of saving millions of lives.
The CPTR Initiative is managed by a partnership of the Critical Path Institute (C-Path), the Bill and Melinda Gates Foundation (BMGF), and the Global Alliance for TB Drug Development (TB Alliance). The CPTR operates under three arms, ie, Regulatory Science Consortium led by C-Path, Research Resources Group led by BMGF, and Drugs Coalition led by TB Alliance.
CPTR Regulatory Science Consortium
The overall goals of the Regulatory Science Consortium involve:
- Establishing consensus among scientists from industry, academia, regulatory authorities and other entities regarding preferred tools for developing new TB drugs and drug regimens;
- Creating innovative drug development tools; e.g., TB data standards, biomarkers and clinical endpoints, preclinical and clinical science tools, and clinical disease progression models; and
- Obtaining qualification of such drug development tools for specific context of use from regulatory authorities.
There are five workgroups (WGs) under the Regulatory Science Consortium and four workgroups under Research Resources; In addition there is a coordinating team, Integrated Sciences Team, which is charged with coordinating all workgroup activities. High-level descriptions of the Integrated Sciences Team and the Consortium WGs are as follows:
Integrated Sciences Team
- Coordinate and align activities among the CPTR Workgroups to assure efficiency and timeliness in accordance with the overall objectives of the CPTR Initiative; and
- Facilitate seamless communication with the Drugs Coalition to best secure its needs are optimally addressed, and with Research Resources to address resource and funding needs.
Data Standards and Integration
- Provide the infrastructure/architecture for all Information Technology systems needs to meet the requirements of the Consortium Workgroups, including standards for data collection and integration, storage, and analysis; and
- Convert all individual project specific data domains and individual data elements to standard useable formats to populate integrated databases, acceptable for regulatory review.
Biomarkers and Clinical Endpoints
- Review and assess the current and emerging science regarding all biomarkers and clinical endpoints used in drug development and regulatory review, regardless of technology platforms: and
- Prioritize the needs, develop consensus, and build the evidence base for biomarker discovery efforts; make recommendations for biomarker qualification for specific context of use.
Preclinical and Clinical Sciences
- Review and assess the current and evolving science regarding optimal preclinical efficacy models, drug safety and toxicology, drug metabolism and interactions, preclinical and clinical PK/PD modeling and simulation: and
- Prioritize the needs and develop better preclinical and clinical tools for specific context of use, including those needed for co-development approaches.
Clinical Disease Progression Modeling
- Develop quantitative clinical disease progression models for use in TB regimen development based on available clinical data, followed by mechanistic model development as new biomarker and other data become available, and clinical trial simulations to aid in trial design for co-development of TB regimens; and
- Create comprehensive pharmacoeconomic models as data becomes available regarding treatment outcomes in different subpopulations and geographic regions.
Health Authority Submission
- Provide guidance during the preparation and submission of any submission packages to health authorities developed by a Regulatory Science Consortium Workgroup, principally those addressing qualification of specific tools for specific context of use; and
- Interact and follow-up with appropriate health authorities during the review process.
Key Regulatory Guidance Documents
Considering the overall goals of the CPTR Initiative, there are two recently issued FDA draft guidance documents that are of particular interest to this Initiative:
- Centers for Disease Control and Prevention
- Colorado State University
- Doctors Without Borders
- European and Developing Countries Clinical Trials Partnership
- Family Health International
- Faster Cures
- Johns Hopkins University
- Johnson & Johnson
- McLaughlin-Rotman Centre for Global Health
- Merck & Co.
- National Institutes of Health / NIAID
- Reagan Udall Foundation
- Resist-TB / Boston University
- St. Michael's Hospital - Toronto
- Treatment Action Group
- University of California / San Francisco
- U.S. Food and Drug Administration
- World Health Organization
C-Path Regulatory Science Consortium for TB Leadership Team
- Debra Hanna, PhD, Executive Director
- Chris Hanson, CAE, Senior Project Manager