A coalition led by the Tucson-based Critical Path Institute (C-Path) to find better treatments for tuberculosis has received crucial backing from the U.S. Food and Drug Administration. The FDA will soon release new policy directives that could cut the approval time for combinations of experimental drugs to treat the world’s most stubborn and deadly diseases by nearly two decades.
TB, HIV, and many varieties of cancer are notoriously resilient in the face of single-therapy treatments, developing resistance that, in the case of communicable diseases, can be passed on through the population, making new cases harder and harder to treat with any one drug. For TB, that pattern has meant that almost all new cases are treated with four drugs simultaneously.
But with each new TB therapy requiring roughly six years of development before approval, and only one drug allowed in the development pipeline at a time, a new four-drug cocktail could take as long as 24 years before it reached patients. Meanwhile, 1.7 million people die each year worldwide, second only to HIV among infectious diseases.
“The FDA has really come on board to try to do some out-of-the-box thinking,” said Ann Ginsberg, chief medical officer of the Global Alliance for TB Drug Development, or TB Alliance, in Businessweek. “In tuberculosis, where the medical need is so urgent and the timelines for development are so long, it just becomes completely impractical to believe you’re going to make advances,” by following traditional protocols.
“We have four to six drugs that people have to choose from today, said Ray Woosley, C-Path’s president and CEO, in a video produced by the TB Alliance. “They have too many side effects, and they don’t really eradicate TB reliably and quickly.” The CPTR [the Critical Path to TB Drug Regimens (CPTR) coalition] will really be an opportunity for the industry, which is committed to developing new combinations of drugs for TB, to work with regulators to create a new paradigm for product development.”
Under the FDA’s new regulations, member firms in the CPTR, jointly sponsored by C-Path, the TB Alliance, and the Bill & Melinda Gates Foundation, will be able to develop drug candidates simultaneously, and will share data from their research and clinical trials with each other. It is the kind of transparent collaboration that has become the hallmark of C-Path, a nonprofit organization founded to make development of therapies faster cheaper, and safer.
“The CPTR initiative is a fundamental commitment on the part of all the partners to the realization that the millions of patients who are dying unnecessarily cannot wait decades,” said Mel Spigelman, president and CEO of the TB Alliance.
“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. “I’ve seen first hand the public health impact and personal tragedy of drug-resistant TB. 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 possible.”
Companies participating in the CPTR include Johnson & Johnson Inc., sanofi-aventis, Pfizer Inc., AstraZeneca PLC, GlaxoSmithKline PLC, Bayer, Otsuka Pharmaceutical Co., Novartis AG, Sequella Inc. and Anacor Pharmaceuticals Inc.
“No single company can do this alone,” said Paul Stoffels, global head of pharmaceutical research and development at Johnson & Johnson, in Businessweek. “What you’re doing now is you get your drug safe and effective and at that moment you can start experimentation,” on combinations with other firms’ drugs.
“This type of collaboration between the public and the private sector is exactly what’s needed to help speed the availability of a shorter and more effective treatment for TB,” said Tachi Yamada, president of the Global Health Program at the Gates Foundation, whose work to eradicate TB has included a $125 million contribution to the TB Alliance. “A successful drug combination regimen to fight TB,” Dr. Yamada said, “could save millions of lives.”
Because of the difficulty in tracing side-effects to their causes in combination treatments involving individual drugs that are themselves still in clinical trials, the new regulations will apply only for those life-threatening illnesses where combination therapies seem most likely to provide improved survival rates over standard-of-care regimens.
“This isn’t for your garden-variety drugs,” said Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, in the Wall Street Journal. “Society wouldn’t tolerate this degree of uncertainty” except where patients face especially steep odds, she said.
The timing is right, though, for the work of the CPTR to accelerate and for the FDA to endorse its approach.
“The real issue for TB has been that it’s a truly neglected disease, and until not that long ago no one was working on new drugs even though there was a clear need for it,” Dr. Spigelman said in Pharm Exec. “We presented this idea five years ago, but there simply weren’t enough compounds to work with.”
For more information:
“Breaking New Ground in the Fight Against TB,” Blog 4 Global Health, 03/18/2010
“A Critical Path to New TB Treatments,” PharmExec.com, 03/18/2010
“J&J, Sanofi, Pfizer Speed Testing for New Tuberculosis Drug,” Businessweek, 03/18/2010
“FDA Is Easing Way for Drug Cocktails,” Wall Street Journal, 03/18/2010
“Global Partners Join Forces to Speed Development of New TB Drug Combinations,” Global Alliance for TB Drug Development news release, 03/18/2010