Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Virulence factor inhibition, a novel approach to treat life-threatening bacterial infections: Challenges for industry, legislation, and agencies ***

Dr. Volker Spehr (Abschlußjahr: 2016)

Summary
Language: English
The fact that many antibiotics have lost their effectiveness in treating bacterial infections causes an urgent medical need to develop new drugs, but the frequency for discovering of new antibiotic classes is low. In addition research to develop novel anti-bacterial drugs and their approvals is declining. The search for new strategies for treatment of MDR bacterial infections discloses antivirulence as innovative new therapeutic concept. In contrast to traditional antibiotics that kill or stop the growth of bacteria, virulence factor inhibitors (VFIs) prevent bacterial colonization and disease formation by neutralizing virulence factors, specific proteins such as toxins required to establish the bacterial infection. Therefore, parallel development of specific in vitro assays to assess the efficacy and the spectrum of activity is required.
Possible antivirulence targets include proteins involved in bacterial adhesion, invasion, colonization, immune response inhibitors, iron acquisition and toxins. For a huge number of these targets small molecule inhibitors were found. Efficacy of these agents in the treatment of bacterial infections has been confirmed in animal models. Approved and marketed antibody-based therapeutics against bacterial toxins serve as proof of concept for the VFI strategy.
All procedural options for marketing authorization application of VFIs might be feasible. Regulatory advice at EMA or discussion with a national competent authority should be considered for clarification.
Development of VFIs is hampered by the lack of guidance by the competent authorities. Only some conclusions can be drawn from guidelines issued for the development of antibiotics, e.g. for characterisation of the safety profile and from guidelines issued for the development of monoclonal anti-bacterial antibodies, e.g. with regard to the design of clinical trials. A request for scientific advice at EMA provided by the SAWP is advisable. Due to the innovative therapeutic concept, the development of VFIs is a challenge for all participants. The success of VFIs is tightly linked to an intensive and collaborative interaction between developers and regulators. Fair compensation of research and development costs is an open issue that has to be mastered by HTA agencies and industry.
Although no VFI has been tested in large scale clinical trials, the antivirulence concept represents a new and fascinating treatment option for bacterial infections, as the case may be caused by MDR pathogens.
Pages: 64