Industry Optimism for Advancing TB Research

Jill Wechsler

Scientists optimistic new combination regimens will improve TB treatment and reduce drug resistance, writes Jill Wechsler, Pharm Exec‘s Washington Editor.

In honor of World TB Day March 24, research organizations and international health agencies announced important advances in the development of new therapies for stemming the spread of increasingly lethal tuberculosis strains. Each year, nearly 9 million people around the world are infected by the disease, and 1.4 million people die. While TB has practically disappeared in the US, co-infection in AIDS patients makes it a serious health concern.

Most of the drugs used today to treat TB were discovered more than 40 years ago and have lost their effectiveness. Poor compliance with lengthy treatment regimens, moreover, has fueled a plague of multi-drug-resistant (MDR) TB strains. In addition, TB diagnostics are antiquated, insensitive and slow, and we have a very limited understanding of TB pathogenesis, says Anthony Fauci, director of the National Institute for  Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH).

Industry support for TB research is limited, Fauci added, because it doesn’t promise blockbuster returns. Within the drug development world, he noted, “TB is not cancer, diabetes or heart disease,” and broad partnerships are needed.
Yet, Fauci expressed optimism for advancing TB research at a recent briefing in Washington, D.C. sponsored by the TB Alliance. Increased investment in TB research by NIAID and NIH has advanced the understanding of treatment effects and the development of molecular markers of drug resistance. Drug pipelines are more robust now than in recent decades, and strong partnerships are tackling translational research projects and building capacity for conducting clinical trials on new TB treatments.

Fauci also highlighted advances in developing a new vaccine to prevent TB in the next decade, noting that existing vaccines are highly ineffective. About 14 vaccine candidates are in development, and more advances may be spurred by the recent publication of a “strategic blueprint” on TB vaccine development by a group of scientists from the public and private sectors.

TB Alliance president Mel Spigelman echoed Fauci’s enthusiasm in announcing the launch of a clinical trial for a novel combination drug regimen that promises shorter, more effective treatment for TB patients, including those experiencing drug resistance. As part of the broader Global Alliance for TB Drug Development, the TB Alliance is sponsoring the NC-002 study to test the PaMZ combination of long-used antibiotic pyrazinamide with Bayer’s Moxifloxacin (not yet approved for TB treatment) and the experimental PA-824. The combination performed well in a limited phase 2A study, and is now expanding to a 2B trial that will test 250 patients at eight sites in South Africa, Tanzania and Brazil. Three other related studies will test additional drug combinations. The Alliance funds these activities through grants from the Bill & Melinda Gates Foundation, NIH, the US Agency for International Development and others.  Scientists also are conducting preclinical tests on a number of new and old drugs to identify other combination regimens suitable for clinical testing. The goal, said Spigelman, is to develop an oral product that reduces treatment to 2-4 months, and ultimately to a simple 10-day regime.

Janet Woodcock, director of FDA’s Center for Drug Evaluation and Research, agreed that “the TB pipeline finally is showing some promise.” FDA is supporting these efforts with new guidance on developing combination therapies that recognizes the need to get away from evaluating one drug at a time. The agency also recently proposed a policy to permit faster approval of new TB diagnostics - another way, said Woodcock,  to capitalize on new efforts for realizing real and significant advances in combating TB.