FDA commissioner announces launch of critical path to TB drug regimens

Recently, FDA Commissioner Margaret Hamburg, MD, addressed a press conference of global representatives from advocacy, industry, academia, and government who convened in Washington, DC, to launch a benchmark international consortium to fight tuberculosis (TB).

This initiative-Critical Path to TB Drug Regimens (CPTR)-was created by a partnership of the Critical Path Institute, the Global Alliance for TB Drug Development, and the Bill & Melinda Gates Foundation. The CPTR goal is to save millions of lives by bringing together scientific, regulatory, advocacy, and government partners to quickly develop new, more effective TB regimens, and make them available to the more than 2 billion affected worldwide, in years, rather than decades.

In her keynote address, Dr. Hamburg recalled her experiences fighting a serious TB outbreak while serving as New York City Health Commissioner in the 1990s. She said that the drugs used then-already 30 years old-are the same ones being used now, and she applauded the goals of the Critical Path consortium for “taking a risk on a disease that has eluded us for far too long.” Dr Hamburg also stated the participatory and crucial role of her agency in these efforts.

“We, at the FDA want to be a gateway, not a barrier, linking scientific opportunity to unmet public health need.” she said.

More than half a century ago, drug regimens were developed to fight and cure TB, but therapy can require up to 4 months commitment with multiple daily tablets. TB often is considered a relic of medical history, but today’s facts are sobering to the opposite. The Global Alliance for TB Drug Development says TB follows HIV as the second leading cause of infectious disease-related death in adults, and the latest World Health Organization’s (WHO) estimates show that one-third of the global population is infected with Mycobacterium tuberculosis that kills nearly 5,000 people each day. However, Dr Hamburg said, it is the surge in drug-resistant strains “that pose a new and larger threat to us all,” which further underscores the need for new, more effective solutions to the current “dizzyingly complex regimen that makes treatment and compliance difficult.” 

Critical Path Institute CEO Raymond Woosley, MD, PhD, said its role with the initiative is to provide the overall coordination and project management of the CPTR’s collaboration. Of the TB drugs in the pharmaceutical pipeline, Dr Woosley said at least 9 promising compounds from several antibiotic classes are in clinical trials or late preclinical development, with others in discovery and early preclinical stages. The most compelling feature of this CPTR collaborative effort is that it will accelerate the development of the most promising of these compounds in combination, rather than individually.  Dr Woosley said FDA’s keen interest in the combination approach and creation of a new, scientifically-based regulatory pathway for this TB initiative will be a unique first, in addressing safety and efficacy of, “not just single agents, but combination therapies.”

“By defining the regulatory pathways for TB combination drug development, you can create the environment you need for any disease,” said Dr Woosley, who forecasts this as a template to enhance future combination efforts and accelerate drug development.

The collaborating partners who Dr Woosley says have endorsed the CPTR Statement of Principles include Sanofi-Aventis, Bayer, Novartis, AstraZeneca, Otsuka, GSK, Anacor, Pfizer, and Johnson & Johnson. Other partnering entities are TB Alliance, European and Developing Country Clinical Trials Partnership (EDCTP), and the Treatment Action Group.

Although many combination treatments look promising, and the exact regimen for the inaugural CPTR trial is yet to be determined, there is expectation of additional compounds that will join forces to their efforts, coming from both the maturation of existing preclinical drugs in development and increased number of participating companies. 

According to Mel Spigelman, MD, CEO, and president of the Global Alliance for TB Drug Development, the CPTR initiative forges a new way of thinking that could revolutionize the process of drug development.

“Testing combinations early in the clinical development promises to bring significantly, not marginally, improved treatment, much sooner,” Dr Spigelman said. “This is hugely important because better and faster treatment regimens are needed to help stop the needless death of 2 million TB patients each year and also to stop the spread of multi-drug-resistant TB, which is already spiraling out of control. With this new approach, and the advances in regulatory science by the FDA, we hope to have a completely new TB drug regimen much sooner than could otherwise have been conceivable.”

Sources
Global Alliance for TB Drug Development. The threat of TB.  http://www.tballiance.org/why/tb-threat.php. Accessed April 13, 2010.

World Health Organization. Tuberculosis. http://www.who.int/mediacentre/factsheets/fs104/en/index.html. Accessed April 13, 2010.