23 July 2012 - Washington, DC - Today, on the occasion of the Internal AIDS Conference, the Global Alliance for TB Drug Development announced findings on a new TB combination drug regimen that promises to dramatically shorten treatment. The new regimen cleared a major hurdle when Phase II clinical trial results published in The Lancet today found it could kill more than 99 percent of patients’ TB bacteria within two weeks and could be more effective than existing treatments. These results add to a growing body of evidence that the new regimen could reduce treatment by more than a year for people with MDR-TB and by at least two months for people with drug-sensitive TB.
The findings from researchers and TB Alliance, which spearheads the Stop TB Partnership’s Working Group on New Drugs, raise hope for a treatment breakthrough in drug-resistant forms of TB which, in some cases, are becoming virtually untreatable. The results also reveal progress in the pursuit of an antiretroviral-compatible TB treatment, which is critical to treating the millions of people with TB/HIV co-infection.
"We congratulate the TB Alliance and all the investigators for this breakthrough, which could translate into a much faster route towards our goal of zero TB deaths," said Dr Lucica Ditiu, Executive Secretary of the Stop TB Partnership. "If the regimen fulfills the promise it has shown to date, its use could result in better adherence to treatment and cure rates for people with drug-resistant TB. For those with MDR-TB it could be a complete transformation from an expensive two-year regimen involving heavy side effects to four months of treatment with a regimen known to cause few side effects. Now we have to look ahead. Provided the new regimen is approved by relevant international bodies we will need to bring together all partners so that we can move forward swiftly towards reaching all who can benefit from it."
The clinical trial tested a combination of one completely novel drug candidate, a new TB drug candidate already approved to treat other infectious diseases, and one existing TB drug. These results, along with pre-clinical data, suggest that this novel combination could treat both drug-susceptible and some forms of drug-resistant TB in only four months.
"These findings confirm the promise of novel TB regimens to be shorter, simpler, safer, and, compared with today’s MDR-TB drugs, much less expensive," said Mel Spigelman, MD, CEO and President of TB Alliance and chair of the Working Group on New Drugs. "The next trial to advance this regimen is already underway. We now have real momentum toward bringing to market treatments that will ultimately help save millions of lives."
TB Alliance’s push to test new drugs in combination has been done to produce a regimen that not only would be faster and easier for patients, but also would tackle two other challenges as a major step in stopping the spread of drug-resistant TB - the complexity and high cost of treatment. This promising regimen eliminates the use of injectables and projects to reduce the cost of MDR-TB therapy by as much as 90 percent.
The study, NC-001, or New Combination 1, was a two-week trial successfully completed at two centers in South Africa. It involved the new combination therapy called PaMZ, consisting of the novel TB drug candidate, PA-824; moxifloxacin, an established antibiotic not yet approved for use in first-line TB therapy and being developed in partnership with Bayer Healthcare AG; and pyrazinamide, an existing TB drug. NC-001 was funded by the Bill & Melinda Gates Foundation, the United States Agency for International Development, UK aid, and Irish Aid.
"Treating drug-sensitive and drug-resistant TB with the same regimen can simplify the delivery of TB treatment worldwide," said Andreas Diacon, MD, the trial’s principal investigator and lead author of the Lancet study. "The results of this study give healthcare providers on the front lines of the TB epidemic hope for better, faster tools needed to stop this disease."
A second trial called New Combination 2 (NC-002) was launched earlier this year to test the PaMZ combination over two months in patients, further advancing it through clinical development. NC-002 is currently enrolling patients and will be conducted at eight sites in South Africa, Tanzania and Brazil, and will build global capacity for TB trials.
The NC-001 trial also validated the approach to development of novel regimens. Mario Raviglione, MD, Director of the Stop TB Department at the World Health Organization, said testing multiple new TB drug candidates simultaneously has already proven to be a major advance. "Because of testing drugs in combination, we have already saved several years in the research process to find new, effective regimens to treat TB," Raviglione said. "The results look strongly promising from this early trial. If further testing holds up these results and the regimen is affordable in poor countries, it is huge progress. We could shorten drug regimens substantially for everyone, regardless of whether the form of TB is sensitive or multi-drug resistant. That would be a dramatic step forward."