Impact of the CPTR Initiative

24 Mar 2010
by Working Group

CPTR could deliver a new TB regimen in just 6 years as opposed to 24

After a decades-long drought, new pharmaceutical discoveries and repurposing of existing antimicrobials have produced about 10 drugs from 7 different classes which are now in various stages of clinical development for TB. Many agents have shown some potential to shorten the duration of treatment in animal models when combined with existing anti-TB drugs. Despite these encouraging developments, it is evident that following the traditional paradigm of substituting one new drug at a time into an existing regimen will require decades to complete the necessary clinical trials and arrive at a truly novel combination, especially given the present limitations on both resources and clinical trial capacity.

In order to deliver sufficiently novel combinations more rapidly, the TB Alliance and others have championed a paradigm shift from “drug development” to “regimen development”, in which new drugs are combined earlier in development to identify promising combinations from the pre-clinical phase through clinical trials and into global usage. This movement is gaining momentum, as evidenced by the Critical Path to TB Drug Regimens initiative (CPTR), a collaboration of TB stakeholders to accelerate the development of transformative drug combinations, launched on March 18th, 2010 with an address by FDA Commissioner Hamburg.

But significant obstacles to developing novel combinations containing 2 or more new unapproved drugs remain, including lack of cooperation among the various sponsors to bring new drugs together, the need for extensive pre-clinical testing to determine the optimal combinations in terms of efficacy and safety, unknowns about the “predictiveness” of existing animal models and regulatory issues regarding assuring the safety and efficacy of such combinations.

The TB Alliance in collaboration with John Hopkins University and University of Illinois at Chicago initiated a preclinical Drug Combination Testing Project in 2007 to addresses some of these obstacles. Through a series of bilateral agreements, the TB Alliance is able to access to the majority of new anti-TB drugs currently in development. Various potential drug combinations have already been or are being tested at UIC and JHU through a rigorous testing algorithm to define the most promising combinations of new and existing drugs for advancement to clinical trials. In the process, the best-performing combinations will be evaluated across different animal models representing a spectrum of lesion types and subjected to combination pharmacokinetic (PK) and toxicology studies expected to enable rapid progression to clinical trials.

For more information:

— Contribution from Khisi Mdluli (TB Alliance)

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