Advancing promising compounds through preclinical and clinical studies for regulatory approval
Found in every country on the map, tuberculosis is the leading infectious cause of death worldwide. Each year, 9.6 million people fall ill from TB and 1.5 million die. The disease disproportionately affects women, children, and those living with HIV infection, and brings with it economic devastation, trapping families and communities in a cycle of poverty and illness. Perhaps more alarming, TB bacteria are becoming increasingly resistant to available drugs, which means the disease is becoming more deadly and difficult to treat.
Current treatment approaches for TB are prolonged, expensive, and sometimes toxic to patients. Treatments for multidrug resistant tuberculosis (MDR-TB) have more in common with cancer therapy regimens than with treatments for other types of infection. Treatment courses can take years, patients may require surgery, and the mortality rate ranges as high as 80 percent.
Despite the rising incidence of TB worldwide, no new drugs for treating drug-sensitive TB and only one new drug for treating multidrug-resistant TB have been introduced to the market in the past 40 years.
Founding a Public-Private Partnership to Advance the Development of New TB Drugs
In 2000, with support from the National Institute of Allergy and Infectious Diseases (NIAID), we joined the Rockefeller Foundation, the Bill and Melinda Gates Foundation, the World Health Organization, and others in founding a global organization to advance the development of new TB drugs.
The Global Alliance for TB Drug Development, or TB Alliance, is a not-for-profit, product development partnership. Together, the partners aim to find and develop drugs that will shorten treatment for TB, make treatment affordable, and provide patients with drug resistant TB with new options and new hope. Today, the TB Alliance manages the largest pipeline of new TB drugs in history.
Delivering Project Management, Research Consultation, and Regulatory Services
Since its inception, our experts have delivered support to the TB Alliance in several critical areas— including integrated planning, study design, implementation, and monitoring for its lead compound PA-824 and other similar projects. We coordinate clinical, nonclinical, and manufacturing studies, and provide expert assistance with statistical analysis and medical writing. Our experts serve as research consultants and source and coordinate additional research expertise from around the world.
We also provide extensive regulatory support, conducting regulatory due diligence and helping manage communications with the U.S. Food and Drug Administration (FDA)—including authorship and assembling of investigational new drug (IND) and orphan drug applications, and other submissions
Managing Development of a Compound that May Help Treat Multidrug Resistant TB
In 2001, we undertook a key role in developing a compound known as PA-824, which showed promise as a treatment for TB infection. Since then, our experts have coordinated the initial due diligence and early studies on the compound and supported a global program for development of PA-824 that includes 26 institutions in nine countries.
In 2005 we helped draft and supported the filing of an IND application with the FDA, and subsequently supported the advancement of PA-824 through Phase I and II trials. In 2007, a 14-day efficacy study was conducted with tuberculosis patients in South Africa and by 2010 studies were initiated with PA-824 in combination with other drugs, which is the standard for TB treatment.
In 2014, PA-824 became known by the name pretomanid. That year we supported the planning of a Phase III clinical trial of an advanced combination regimen that includes pretomanid, moxifloxacin and pyrazinamide. Known as PaMZ, this is the first-ever drug regimen designed to treat both drug-sensitive and some forms of multidrug resistant TB.
In 2015, PA-824 moved into Phase III trials, and we continue to support the TB Alliance, serving as the regulatory contact with the FDA. The trial—named Shortening Treatments by Advancing Novel Drugs or STAND—spans more than 50 study sites across Africa, Asia, Eastern Europe, and Latin America. Not only is this study a major milestone in the development of a potential regimen for MDR-TB, it could also help open a regulatory pathway for new combination trials.
Continued Dedication to a Shared Mission
We are proud to continue our service to the TB Alliance, supporting five of its ongoing drug development programs, including pretomanid. Our ongoing work has the potential to extend beyond the fight against tuberculosis to advance global efforts to combat antibiotic and antimicrobial resistance of other bacteria.
The challenges of developing new affordable medicines for the world's poorest populations are significant. But we believe that, by working creatively in partnership with international public and private entities, we can overcome these challenges and, in time, bring badly needed medicines through the drug development pipeline.
