New tuberculosis drug set for global phase 3 clinical trial

Based on positive results from earlier clinical studies, TB Alliance is advancing the first-ever drug regimen designed to treat both drug-sensitive and some forms of multi-drug resistant tuberculosis (TB) to a global Phase 3 clinical trial.

The announcement by Bill Gates, co-chair of the Bill & Melinda Gates Foundation, accompanied a commitment of significant funding by the Gates Foundation to determine the safety and efficacy of the new drug regimen, which is known as PaMZ. Mr. Gates called on other organizations to support the effort to develop new treatments for TB, a disease that kills an estimated 1.3 million people annually and remains a leading cause of death globally, especially among people who are co-infected with HIV.   

"The results from early phase research suggest that this new drug regimen could provide the breakthrough we need to accelerate progress against this deadly and dangerous disease," said Mr. Gates. "PaMZ could dramatically reduce the time required to cure drug-resistant TB from two years to just six months, and it could cut the cost of curing drug-resistant TB in low-income countries from thousands of dollars to just a fraction of that cost. Now we need funders to step forward to make next-generation TB drugs like PaMZ a reality."

Limitations in standard treatment for TB remain a strong barrier to TB control. The treatment and cure of a typical case of drug-sensitive TB currently takes between six and nine months and the drug therapy is long, complicated, and can cause severe side effects. Currently, people with drug-resistant TB require a minimum of 18 to 24 months of treatment. This more extensive therapy requires more than 12,000 pills and daily injections for at least 6 months. The long duration of MDR-TB treatment, combined with the pain and side effects that treatment causes, help to explain why only just over half (53 percent) of patients who currently enter therapy for MDR-TB complete their full course of medicines.

The PaMZ regimen shows promise to significantly shorten therapy, particularly for some forms of MDR-TB. It will be tested in a Phase 3 clinical trial named STAND (Shortening Treatments by Advancing Novel Drugs). If successful, the regimen would eliminate the need for injectable drugs and reduce the cost of MDR-TB therapy in some countries by more than 90 percent in those patients whose TB organisms are sensitive to the three drugs. It also promises to be compatible with commonly used HIV drugs, helping the millions of people co-infected with TB/HIV.

“TB patients, especially those with drug-resistant TB, urgently need cures  that eliminate the need for injectable therapies, require taking fewer pills for a shorter period of time, are less toxic, simpler to administer and cost much less money,” said Dr. Mel Spigelman, president and CEO of TB Alliance, an international non-profit working to develop improved TB treatments. “The STAND trial brings us closer to an era of high-impact drug regimens instead of where we are today, relying on the relics of the mid-20^th century.”

The STAND trial will span some 50 study sites across Africa, Asia, Eastern Europe and Latin America. It will test the novel three-drug regimen PaMZ as a shorter, simpler and safer treatment for drug-sensitive and drug-resistant TB. The development of the PaMZ regimen is projected to save years of time by having tested new drugs simultaneously as a “drug regimen” instead of one-by-one.

PaMZ is a three-drug regimen comprised of two candidate drugs that are not yet licensed for use against TB: PA-824 (Pa) and moxifloxacin (M), and one existing antibiotic used in TB treatment today, pyrazinamide (Z). Earlier study results show PaMZ’s potential to treat both drug-sensitive and drug-resistant patients with the same oral therapy, and to dramatically shorten treatment times for some patients. In July 2012, a two-week study published in The Lancet showed that PaMZ appeared to kill the patients’ bacteria more quickly than standard therapy after starting treatment. Findings from a subsequent two-month study are expected to be published later this year.

Support for earlier research of the PaMZ regimen was provided by the Bill & Melinda Gates Foundation (BMGF), the United Kingdom Department for International Development (DFID), the Australia Department for Foreign Affairs (DFAT), US Agency for International Development (USAID), Irish Aid, and the Directorate-General for International Cooperation (DGIS).

While the TB Alliance hopes to launch the STAND trial by the end of this year, Spigelman noted the date will be subject to obtaining adequate funding commitments.

“We thank all our supporters to date, as without their investment, the highly promising PaMZ regimen would not have reached this critical stage,” said Spigelman. “We need new and expanded commitments for the STAND trial, however, if we are to realize the significant potential of this treatment to save millions of lives.”