The first phase of the trial, at specialist sites in South Africa, confirmed the safety of increasing doses of BTZ-043. The second phase confirmed its excellent bactericidal activity, identified a significant food effect (high-fat food leads to better absorption), and detected some minor changes to drug-metabolising enzymes, which would likely have minimal clinical impact on co-administered drugs.

The trial results strongly support further development of BTZ-043, and have provided key information to underpin the design of future trials. The PanACEA STEP2C phase IIB trial is evaluating BTZ-043 as an

alternative to ethambutol. It is also being studied in the phase IIB DECISION and PARADIGM4TB studies, through the UNITE4TB programme.

The innovative study design was a highly efficient way of gathering a large amount of key data in a single study, in people with newly diagnosed TB – optimising the use of resources and accelerating clinical development.

A combination of PSIA funding and the EDCTP2-funded PanACEA network is accelerating development of BTZ-043, a promising new treatment for TB.

More than 10 million cases of TB occur each year, leading to over a million deaths. It requires extended treatment with multidrug cocktails, and there are growing concerns about the emergence of resistance to components of these regimens. New TB drugs are thus urgently needed.

Through Participating States-Initiated Activities (PSIA) funding, a team in Germany has developed a possible new TB drug, BTZ-043, based on a novel target – DprE1, an enzyme involved in synthesis of the mycobacterial cell wall. Following successful first-in-human studies in Germany, the EDCTP2-funded PanACEA network is now evaluating its safety and efficacy in TB-endemic countries in sub-Saharan Africa.

Using an innovative trial design, the PanACEA team has conducted a two-part phase IB/IIA trial to investigate the safety and efficacy of different doses of BTZ-043, the impact of fed or fasting state, and its potential to affect the metabolism of other drugs.