FDA Approves Breakthrough Drug to Treat Extensively Drug-Resistant Tuberculosis

RESEARCH TRIANGLE PARK, N.C. — Today, the Food and Drug Administration (FDA) announced its approval of pretomanid, a new drug developed to treat Extensively Drug-Resistant Tuberculosis (XDR-TB) and treatment intolerant/non-responsive Multidrug-Resistant (MDR) TB. RTI International (RTI) scientist Dr. Doris Rouse and her team have collaborated closely with TB Alliance on the development of pretomanid for almost 20 years. TB Alliance is a non-profit product development partnership that RTI and Dr. Rouse helped to form in 2000. TB Alliance has negotiated license agreements enabling an affordable cost of pretomanid in low resource countries.

“We are seeing an increase in XDR-TB, and we need new weapons to attack it,” Rouse says. “I've been in wards with patients that are so emaciated, they won't eat anything, they have fevers, they can't sleep. But with pretomanid, in a regimen that includes two other drugs, bedaquiline and linezolid, we see improvement within a few weeks. This new treatment will help people who have no other good option for a cure.”

Pretomanid is only the third anti-TB drug approved by FDA in more than 40 years. Prior to the pivotal Nix-TB trial of pretomanid as part of a three-drug regimen with bedaquiline and linezolid (known as the BPaL regimen), treatment for XDR-TB required a two-year regimen and in South Africa, for example, only cured 2 to 22 percent of those receiving treatment. The six-month, all-oral BPaL regimen cured approximately 9 out of 10 participants of the XDR-TB patients in the trials conducted in South Africa.

Tuberculosis kills 1.6 million people a year — more than 4,000 people a day — and kills more people than any other infectious disease. XDR-TB is resistant to four of the main drugs, including injectable agents, currently used to treat drug resistant TB around the world.

With funding from the National Institute of Allergy and Infectious Diseases (NIAID), in 1999 Rouse and a team at RTI headed up the effort to identify potential new compounds for TB treatment. They identified and conducted due diligence on pretomanid, a compound developed by a small biotech, Pathogenesis.

TB Alliance acquired the license to pretomanid, then known as Pa-824, in 2002. RTI assisted TB Alliance in planning and managing the preclinical studies needed for development and preparing the successful Investigational New Drug (IND) application to FDA in 2005, leading to the start of clinical trials that year.

RTI has served as a regulatory contact for TB Alliance since the pretomanid IND was submitted to FDA in 2005.

“We’ve worked on this new drug for 19 years, and it hasn’t always been an easy path,” she added. “But as I’ve always said, ‘One of the main ingredients for successful drug development is blessed stubbornness.’ This public-private partnership is an excellent model for meeting unmet needs, especially those that are in low-resource countries that may not have the commercial attraction of other diseases.”

TB Alliance is now targeting adoption and availability of pretomanid as part of the BPaL regimen in countries with a high unmet need for XDR-TB treatments.