such as tuberculosis and HIV
must be treated with combination
therapy in order to fully suppress pathogens and prevent emergence
of drug resistance, but testing individual agents in a multi-drug
regimen presents challenges.
date, the FDA has required that each drug in a regimen must be
tested and approved individually, with each successive agent added
to a background regimen of existing approved drugs. But it can
be difficult to demonstrate the independent efficacy of a single
agent in a regimen with other active drugs, as
shown recently in the case of Merck's investigational CCR5
Sciences is currently developing a 4-in-1
combination Quad pill in which one of the ingredients -- the
experimental boosting agent
cobicistat (GS 9350) -- has no anti-HIV activity of its own,
and the company plans to seek approval of cobicistat in conjunction
with the other drugs.
Now, a public-private collaboration known as Critical Path to
TB Drug Regimens has launched to test combinations of investigational
tuberculosis drugs from different companies early in the development
pipeline. About 10 promising anti-TB candidates from at least
6 antibiotic drug classes are currently in clinical trials or
late preclinical development.
The collaboration was created by the Global Alliance for TB Drug
Development, the Critical Path Institute, and the Bill & Melinda
Gates Foundation, and includes FDA representatives and researchers
from several pharmaceutical companies including Anacor, AstraZeneca,
Bayer, GlaxoSmithKline, Johnson & Johnson, Novartis, Otsuka,
Pfizer, Sanofi-Aventis, and Sequella. GlaxoSmithKline and Pfizer
have also formed a partnership, called ViiV Healthcare, to work
together to develop HIV therapies.
The new TB collaboration will welcome participation from any company
with a promising drug candidate in development, as well as other
companies and organizations with the technical expertise or resources
to help develop new TB regimens.
The initiative could potentially reduce the time it takes to introduce
new combination TB treatments from as much as a quarter century
to as few as 6 years, according to the Alliance. The initiative
has the commitment of the FDA and regulatory authorities in Europe
"to help develop and validate improved, safe, and accurate
regulatory pathways to test and register combination TB treatments."
"FDA is absolutely committed to working with partners to
speed access to new, safe and highly-effective treatments for
TB, which continues to mutate and spread," said FDA commissioner
Margaret Hamburg in a press release issued by the Alliance. "This
creative approach mirrors FDA's own investments in innovative
regulatory science that ensures the best new medical technologies
-- including combination therapies -- reach patients as soon as
"With its leadership on TB, FDA is poised to repeat its creative
regulatory approach to AIDS drugs in the 1990s, which helped save
the lives of millions without compromising drug quality,"
said Mark Harrington of Treatment Action Group.
Some experts, however, think the approval mechanism for HIV drugs
is itself due for an overhaul now that more than 20 antiretroviral
drugs are available to build effective combination regimens, making
it harder for a new candidates to stand out even if they work
as well as existing agents.
For more information about the Critical Path Institute, please
For more information about the Global Alliance for TB Drug Development,
please visit www.tballiance.org.
Family Foundation. FDA Drafts New Rules for Testing, Approving
Drug Cocktails; Public-Private Partnership for TB Treatment Development
Daily Global Health Policy Report. March 18, 2010.
Schoofs. FDA Is Easing Way for Drug Cocktails. Wall
Street Journal. March 18, 2010.
Alliance for TB Drug Development. Global Partners Join Forces
to Speed Development of New TB Drug Combinations. Press release.
March 18, 2010.