In the lead up to World Tuberculosis (TB) Day this Saturday, March 24, the TB Alliance announced the launch of a new trial to test a combination drug regimen in patients with drug-sensitive TB as well as patients with multidrug-resistant (MDR) TB – the first time this has ever been done.
Called “NC-002,” the eight-week trial will assess two drugs not approved for TB treatment – PA-824 and moxifloxacin – used in combination with generic pyrazinamide (or PaMZ, which has been approved for TB treatment)in an oral, once-daily regimen at eight trial sites in Africa and South America, said Mel Spigelman, MD, president and CEO of the TB Alliance. One arm will look at patients with drug-sensitive TB, one at patients with drug-resistant TB, and another at patients with multidrug-resistant (MDR) TB, and compare them against standard therapy.
Spigelman announced the Phase IIb trial launch at an event hosted by the Critical Path to TB Drug Regimens Monday focusing on the most promising TB drug research. The initiative was launched in March 2010 and is working to create a new TB drug development “paradigm that enables promising combinations of drugs to be tested and developed together to create entirely new multi-drug regimens,” according to the initiative’s website. Critical partnerships allow combination drug development to proceed and make it to the clinic much faster, Spigelman said.
TB killed 1.4 million adults and children in 2010 and it is the leading killer of people with AIDS, said Christine Lubinski, Vice President of Global Health at the Infectious Diseases Society of America, who moderated the panel of experts at the Kaiser event. There are 650,000 people living with multidrug-resistant TB (MDR-TB) and it is estimated that less than ten percent of them are receiving adequate treatment, which currently consists of daily injections for the first six months and 12 or more pills per day for 18 months or more. The length, complexity and severe side effects of treatment are major contributors to low regimen adherence – as well as the lack of physicians trained to adequately treat TB in some parts of the world. These exacerbate the rise in drug resist forms of TB.
“It’s clear we require these coalitions to make progress,” said Dr. Janet Woodcock, director of the Food and Drug Administration’s Center for Drug Evaluation and Research, who also participated in the panel discussion. “Six-month treatment requirements are a set up for failure in poverty stricken parts of the world. We don’t just need new therapies, we need short effective regimens.”
Of the several promising attributes of NC-002, Spigelman said the trial is funded through various sources – Bayer, the U.S. Agency for International Development (USAID), The Bill & Melinda Gates Foundation – spreading out the financial burden involved in developing a new drug, which these days costs $1 to $2 billion. The new combo drug would shorten treatment to four months – an amazing advance in drug-resistant TB treatment that would reduce treatment time by 80 percent and reduce the cost of treatment by 90 percent. None of the drugs in the combination regimen has interactions with any of the antiretroviral drugs, making it compatible with HIV treatment and increasing doctors’ ability to treat the two diseases simultaneously, dramatically easing delivery and distribution logistics, Spigelman said. TB remains the number one killer of people living with HIV and is endemic in parts of sub-Saharan Africa. The study results will be available about one year from now, and if positive the study will move directly into pivotal phase three clinical trials. This is also the first attempt to test whether there is a biologic difference between drug-sensitive and drug-resistant patients, Spigelman said, and it could transform the whole approach to therapy.