Do you believe the PDP structure is still relevant now that the TB Alliance is entering its second decade?
MS: Yes—more than ever, given the growing need to leverage multiple public and private sources of funding and partnership. What
we need is not just the discovery of individual new drugs, but the coordinated efforts of all drug sponsors and relevant institutions
to make the process of new therapy development and introduction faster, cheaper, and better. We will never defeat TB unless
we make that happen. Today, we have multiple companies who are willing to work and even test their drugs together, and coordinated
efforts in multiple spheres on the parts of government institutions, academic centers of excellence, and even civil society.
The strategy is embedded in the Critical Path to TB Drug Regimens (CPTR) initiative, where we work with major drug companies,
regulators, multilateral institutions like the World Health Organization (WHO), and a variety of other partners to streamline
competencies around developing and making available shorter, more effective multidrug therapies. In another partnership, the
TB Alliance is working with the CDC and the NIAID with funding from the FDA and the Bill and Melinda Gates Foundation to set
up a mechanism through which biomarkers for TB could be quickly identified and validated. Effective new biomarkers for TB
treatment effects could revolutionize the process of TB drug R&D
These examples provide some metrics to demonstrate to Big Pharma that working with you is not an exercise in irrelevance.
MS: We should rename the PDP concept and call it instead the PIP: the Product Impact Partnership. Our true goal is not development of products, but [maximization of] the impact of the products we develop. Impact
is also critical in today's challenging economic climate, when it is more important than ever to demonstrate a significant
return on investment, whether one uses public or private resources.
Perhaps the greatest challenge we face today is that of tremendously constrained resources. Given the scope of the challenge,
TB drug R&D is still woefully underfunded. The Gates Foundation has been essential to the financing effort, as the Alliance
would likely not exist without Gates Foundation support. However, when you compare even the total Gates Foundation support
of all PDPs to what Big Pharma spends every year just on R&D, it becomes obvious that multiple other mechanisms of support
are necessary. And we also should not forget the leveraging capacity of organizations like the TB Alliance; through a variety
of mechanisms, the total cost or value of TB Alliance programs is more than twice our investment—meaning every dollar given
to the TB Alliance produces roughly $2 in impact.
Can you identify the Alliance's most promising compounds in development?
MS: NC001 is the first Phase II, proof-of-concept study of a novel regimen that combines two new or unapproved TB compounds,
PA-824 and moxifloxacin, with one current TB drug, pyrazinamide. The results of our recently completed study of this regimen
are very exciting, as this regimen does not include the established older drugs, isoniazid or rifampicin, resistance to which
defines multidrug resistant TB (MDR TB). As predicted in the preclinical models, this regimen appears to perform at least
as well as our best standard therapy for drug-sensitive TB. This would be particularly important for MDR TB, where the current
therapy now takes more than two years to treat and is so complex and expensive that less than 10 percent of patients with
MDR TB are presently even treated. The new combination would cost a fraction of what health systems pay now. Similarly, the
data emerging from NC001 are equally encouraging on the results of a combination of a novel drug discovered by Johnson&Johnson's
Tibotec subsidiary, called TMC207, when that drug is combined with pyrazinamide.