Researchers reported in The Lancet that the novel regimen PaMZ showed superior bactericidal activity in tuberculosis compared with standard care over the course of 8 weeks, moving one step closer to possibly shortening treatment for patients with the disease.
PaMZ is a combination of two drugs currently unapproved for TB — moxifloxacin and pretomanid, formerly known as PA-824 — and pyrazinamide. It is intended for patients with both drug-susceptible and multidrug-resistant TB (MDR-TB).
“The results of this trial show the potential for the PaMZ regimen to improve treatment for tuberculosis,” Rod Dawson, MD, head of the Centre for TB Research Innovation at the University of Cape Town, South Africa, said in a press release. “Especially noted is the fact that PaMZ may have a unique application as a potentially shorter, injection-free regimen for a select sub-group of patients with MDR-TB.”
In the phase 2b clinical trial, Dawson and colleagues assessed the efficacy and safety of PaMZ in the first 8 weeks of treatment of 207 patients with pulmonary TB at eight sites in South Africa and Tanzania. Participants with drug-susceptible TB (n = 181) were randomly assigned to PaMZ with either 100 mg or 200 mg pretomanid, or standard care with isoniazid, rifampicin, pyrazinamide and ethambutol (HRZE). A small group of participants (n = 26) with MDR-TB were given PaMZ with pretomanid 200 mg or standard care. Forty participants had HIV.
The researchers measured bactericidal activity by the rate of reduction of Mycobacterium tuberculosis in sputum samples collected from participants each week, using both solid and liquid media culture.
Almost twice as many participants with drug-susceptible TB (71%) were culture-negative after 8 weeks of treatment with PaMZ compared with those taking HRZE (38%). Similar results were observed in participants with MDR-TB, but conclusions are limited due to the small sample size. However, when taken together with evidence from earlier preclinical studies, PaMZ shows promise in shortening treatment to 4 to 6 months for patients with drug-susceptible and MDR-TB, according to the researchers.
Standard care of TB takes approximately 6 to 9 months, and for patients with drug-resistant TB, a minimum of 18 to 24 months.
Additionally, PaMZ appeared to be effective regardless of HIV status.
“PaMZ is the first regimen under development to treat both drug-sensitive TB and MDR-TB,” Mel Spigelman, MD, president and CEO of TB Alliance, said in the release. “If successful, PaMZ could be a shorter, simpler and safer treatment that would enable the scale-up of treatment.”
All regimens were well tolerated and safe, the researchers said, and adverse events were similar across treatment groups. The most common disorder was hyperuricemia (29%), followed by nausea (18%) and vomiting (12%).
According to TB Alliance, which sponsored the study, enrollment has begun for the phase 3 STAND trial, which is expected to include 1,500 patients in 15 countries in Africa, Asia, the Caribbean, Eastern Europe and Latin America. PaMZ will be tested in patients with both drug-sensitive and drug-resistant TB, with the goal of shortening and simplifying treatment. – by John Schoen
Disclosure: The researchers report no relevant financial disclosures.