The new antibiotic BTZ-043 has a completely new mechanism of action and belongs to a new class of substances. It is currently the only new antibiotic from Germany that is being tested in clinical trials. Discovered at the Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI) in Jena, the active substance has been under development since 2014 in collaboration with the Tropical Institute at LMU Klinikum Munich and Hapila GmbH in Gera. BTZ-043 has now been named Leibniz Drug of the Year 2023 at the Leibniz Wirkstofftage in Braunschweig.
While tuberculosis has become relatively rare in Germany and other industrialized nations, around 10 million people contract the bacterial infection every year, particularly in poorer countries. Tuberculosis is thus the most common bacterial cause of death worldwide. According to the World Health Organization (WHO), it kills around 1.6 million people every year, particularly in Southeast Asia, Africa and the Western Pacific region. Infection is particularly dangerous for people with a weakened immune system; HIV-infected people are especially affected.
In addition to a lack of medical care in poorer countries, the increasing number of resistances to common tuberculosis therapies is problematic. At the same time, hardly any new antibiotics are being developed. The nitrobenzothiazinones (BTZs) discovered and developed at Leibniz-HKI are a very effective class of antibiotics against the tuberculosis pathogen Mycobacterium tuberculosis, including resistant strains. BTZ-043 was the first member of this family of compounds to obtain worldwide patent protection for its activity against the tuberculosis pathogen. "The active ingredient irreversibly binds to an enzyme that mycobacteria need to build the bacterial cell wall," explains Florian Kloß. As former head of the Transfer Group Anti-infectives at Leibniz-HKI, he played a key role in the development of the active substance.
First clinical trials successful
The substance, which has now been named drug of the year, has already successfully undergone initial clinical trials. A Phase I study conducted in Germany on healthy volunteers showed that BTZ-043 was well tolerated. The subsequent Phase IIa clinical trial was conducted in tuberculosis patients in Cape Town, South Africa. It confirmed BTZ-043 as safe and effective - an important step in the development of a new drug. Further Phase II clinical trials are currently being planned to investigate BTZ-043 in combination with various standard antituberculotics. This means that it is now within reach that BTZ-043 could replace one of the conventional antibiotics, which are often susceptible to resistance, in a combination therapy, and shorten the duration of treatment for tuberculosis.
For the preclinical and clinical studies, Leibniz-HKI has been cooperating closely with the Tropical Institute at LMU Klinikum München since 2014. They are commissioned and supervised by the director of the Tropical Institute, Professor Michael Hoelscher and his team. The highly effective substance is manufactured at a medium-sized pharmaceutical company, Hapila GmbH in Gera, Germany.
The drug development, which costs several million euros, is only possible thanks to joint funding from the public and private sectors. In particular, the two research networks InfectControl and the German Center for Infection Research (DZIF), which are funded by the German Federal Ministry of Education and Research (BMBF), are involved in the drug development. The clinical trials take place within the European-African consortium PanACEA II, funded through the European & Developing Countries Clinical Trials Partnership (EDCTP), and the research consortium “Academia and Industry United Innovation and Treatment for Tuberculosis” (UNITE4TB). The latter is supported at the European level by the Innovative Medicines Initiative (IMI), a public-private collaboration now known as the Innovative Health Initiative (IHI), and at the German level by the BMBF*.
In addition to Florian Kloß, Sina Gerbach and Freddy Bernal were honored with the award. While Kloß primarily led the chemical aspects of the preclinical and clinical development of BTZ-043 and was involved in several patent applications and publications, Gerbach led the contract research on drug safety and in vitro studies on potential drug-drug interactions, which are required for drug approval. Bernal developed computer models to study the relationship between the structure of benzothiazinones, their physical properties, and their efficacy.
https://www.gesundheitsforschung-bmbf.de/de/btz-043-moglicher-gamechanger-im-kam... - *More information on BTZ-043 and funding
The molecular structure of the active ingredient BTZ-043, a new antibiotic against tuberculosis.
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