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New TB Drug Regimen Moves to Phase III Trial

Study will test first therapy for both drug-sensitive and drug-resistant disease

Based on positive results from earlier clinical studies, the first-ever drug regimen designed to treat both drug-sensitive and some forms of multidrug-resistant tuberculosis (TB) is being advanced to a global phase III 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, known as PaMZ. 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 human immunodeficiency virus (HIV).

The treatment and cure of a typical case of drug-sensitive TB currently takes between 6 and 9 months, and the drug therapy is long, complicated, and can cause severe adverse 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 treatment for multidrug-resistant TB, combined with the pain and side effects that the treatment causes, help to explain why only 53% of patients who currently enter therapy for multidrug-resistant TB complete their full course of medications.

PaMZ is a three-drug regimen consisting of two candidate drugs that are not yet licensed for use against TB — PA-824 (Pa) and moxifloxacin (M) — and one antibiotic currently used in TB treatment, pyrazinamide (Z).

Earlier study results demonstrated the potential of the PaMZ regimen 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 2-week study published in The Lancet showed that PaMZ appeared to kill the patients' bacteria more quickly than did standard therapy after starting treatment. Findings from a subsequent 2-month study are expected to be published later this year.

The PaMZ regimen will now be tested in the phase III STAND (Shortening Treatments by Advancing Novel Drugs) trial. If successful, the regimen would eliminate the need for injectable drugs and would reduce the cost of managing multidrug-resistant TB in some countries by more than 90% in patients whose TB organisms are sensitive to the three drugs. PaMZ also promises to be compatible with commonly used HIV treatments, helping the millions of people co-infected with TB and HIV.

The STAND trial will be conducted at study sites in Africa, Asia, Eastern Europe, and Latin America. The study will test the PaMZ regimen as a shorter, simpler, and safer treatment for patients with either drug-sensitive or drug-resistant TB. The development of the PaMZ regimen is projected to save years of time by having tested the new drugs simultaneously as a single treatment regimen instead of one-by-one.

While the STAND trial is expected to be launched by the end of this year, the date will be subject to obtaining adequate funding commitments.

Source: TB Alliance; April 23, 2014.

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