The first new drug combination for treating tuberculosis (TB) has cleared a major hurdle: results of a phase II clinical trial published this week in The Lancet show it killed more than 99% of patients’ TB bacteria within 2 weeks.

The study suggests the new drug combination could be more effective than current treatments.

The achievement is a significant milestone in the search for new drugs to fight TB, and saves years of research, say the non-profit TB Alliance, who ran the trial with other researchers.

The prospective, randomised trial tested PaMZ, the new combination TB therapy, which comprises three drugs:

  • Drug 1: PA-824, a novel TB candidate.
  • Drug 2: moxifloxacin, an established antibiotic not yet approved for use in first-line TB therapy and being developed in partnership with Bayer Healthcare AG.
  • Drug 3: pyrazinamide, an existing TB drug.

The study, known as New Combination 1 or NC-001, was a 2-week trial involving 85 patients and took place at two centers in South Africa. It was funded by the Bill & Melinda Gates Foundation, the United States Agency for International Development, UK aid, and Irish Aid.

Another trial, New Combination 2 (NC-002), launched earlier this year, is also testing PaMZ. That trial is over 2 months, and is currently enrolling participants in South Africa, Tanzania, and Brazil. The idea is to build up global capacity to carry out trials.

Remarkably, the 3-in-1 combo seems to work just as well against drug-resistant strains of TB, which are now spreading around the world.

The results of the trial, with some pre-clinical data, suggest it could treat drug-resistant TB in just 4 months.

Currently, it takes 18 to 24 months to treat people with multi-drug resistant TB (MDR-TB). Even those with drug-susceptible TB need 6 months of taking drugs every day.

Mel Spigelman, CEO and President of TB Alliance, told the press:

“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.”

TB Alliance estimate the new regimen would eliminate the use of injectables and could slash the cost of MDR-TB therapy by as much as 90%.

Study first author and lead investigator Andreas Diacon, from Stellenbosch University, Cape Town, South Africa, said:

“Treating drug-sensitive and drug-resistant TB with the same regimen can simplify the delivery of TB treatment worldwide.”

“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,” he added.

TB is currently the biggest killer of people with AIDS.

The study findings were announced on Monday at the 2012 International AIDS Conference, which is taking place in Washington DC, USA, this week.

The results also reveal progress in the search for an antiretroviral-compatible TB treatment, which is critical for the treatment of millions of people co-infected with TB and HIV.

TB and HIV treatments often cannot be given together because of problems of drug interactions and bad side effects.

A significant outcome of the trial is that it could be a potential game-changer for drug development.

The trial is the first time that more than one unapproved drug has been tested at the same time. This could prove a successful approach for future drug development.

TB experts say any new drugs for tuberculosis would be an extraordinary development, but that new TB drug combinations are potential game-changers due to their expected impact.

In addition to these results, drug companies are seeking regulatory approval for individual TB drug candidates. Such advances are made possible by the existence of the most promising research pipeline for TB drugs in history, say TB Alliance.

Mario Raviglione, Director of the Stop TB Department at the World Health Organization, said:

“Because of testing drugs in combination, we have already saved several years in the research process to find new, effective regimens to treat TB.”

“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,” he added.

Spigelman said:

“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.”

Every year, 9 million people around the world find out they have TB.

One in three people, that is nearly 2.5 billion humans, carry a latent form of the disease, which kills around 1.4 million every year.

Written by Catharine Paddock PhD