Developing New Treatments
Pretomanid Begins Evaluation for FDA Approval
A new TB treatment is under regulatory review. On December 14, 2018, TB Alliance submitted its first New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA). The FDA has now accepted TB Alliance’s application for pretomanid and granted it Priority Review, with a decision expected to be rendered in third quarter 2019.
The application is for the use of pretomanid as part of an investigational drug regimen, in combination with bedaquiline and linezolid, for the treatment of extensively drug-resistant (XDR) TB, treatment-intolerant multidrug-resistant (MDR) TB, and treatment non-responsive MDR-TB. The regulatory submission of the pretomanid NDA is the result of significant commitments from donors, partners and community members.
The chemical structure of pretomanid
Three Late-Stage Clinical Trials Advancing Tomorrow's Cures
TB Alliance is working to introduce promising new TB treatments for all forms of the disease. In 2018, we concurrently led three late stage Phase 3 trials—each is expected to offer scientific insights that could impact the global epidemic.
Last year, the 109th and final participant in the Nix-TB clinical trial reached the primary endpoint. Nix-TB participants with XDR-TB and treatment-intolerant or non-responsive MDR-TB were treated with the BPaL (bedaquiline + pretomanid + linezolid) regimen for six months, or extended to nine months in some cases, with the intent to cure. Nix-TB is an open-label, single arm trial. In interim results on the first 75 participants presented at the presented at the 2018 Union World Conference on Lung Health, 89 percent of the trial participants had a favorable outcome with their clinical infection resolved and sputum cultures negative for TB after six months of treatment and six months of post-treatment follow-up.
Launched in late 2017, the ZeNix clinical trial progressed substantially throughout 2018, attaining over 40 percent of its planned enrollment. ZeNix is a successor to Nix-TB and is evaluating lower doses and shorter durations of the drug linezolid in a modified BPaL regimen. If successful, this could enable BPaL to be used more broadly in people with TB, including those with less severe drug-resistance profiles. We expect to complete enrollment in 2019.
Launched in August 2018, SimpliciTB is a pivotal trial evaluating the potential of the BPaMZ (bedaquiline + pretomanid + moxifloxacin + pyrazinamide) regimen to shorten treatment for both drug-sensitive and drug-resistant TB. SimpliciTB is evaluating whether BPaMZ can treat drug-sensitive TB in four months—compared to the six-month standard treatment—and DR-TB in six months—compared to the current 9–20+ month treatment options. By the end of 2018, more than 50 patients were enrolled across nine sites. The trial is ultimately slated to span 26 sites in 10 countries.
Pioneering Clinical Research in South Africa
Dr. Francesca Conradie is the principal investigator of Nix-TB, TB Alliance’s first Phase 3 trial evaluating the BPaL regimen. Throughout her career, Dr. Conradie has been a part of the research agenda that brought effective antiretroviral therapy to millions of South Africans living with HIV. Now, she is focused on TB research, especially new treatment strategies for drug-resistant TB. She has also been instrumental in the adoption of bedaquiline in the South African market. Conradie presented interim Nix-TB results at the 2018 Union Conference.
View Dr. Conradie’s presentation of interim Nix-TB data at the 2018 Union Conference