In the field of intensive care medicine Biotest is developing trimodulin, for the treatmen of patients with severe community acquired pneumonia (sCAP). Trimodulin (BT588, predecessor BT086) is a human plasma-derived native polyclonal antibody preparation for intravenous administration. Trimodulin contains immunoglobulins IgM (~23%), IgA (~ 21%) and IgG (~56%). The novel drug trimodulin mediates its mode of action via three potential mechanisms such as opsonization of causal pathogens, neutralizing of microbial pathogens and their virulence factors (endo and exo toxins) as well as targeting of the host inflammatory response (anti-inflammatory properties). Those mechanisms are mediated by the three components of the immunoglobulin drug.
In in-vitro systems it was demonstrated that trimodulin acts through a range of mechanisms which are expected to counteract the pathophysiological processes which can otherwise lead to severe respiratory disturbances, severe sepsis with multi organ failure and to the death of patient. Besides the depicted potential mode of action, successful patient treatment is achieved by combined binding of sCAP-related pathogens.
In the finalized Phase II CIGMA study, the efficacy and safety of trimodulin as add-on therapy to standard care (verum) in patients with sCAP versus placebo plus standard of care (placebo) was investigated. In post-hoc analyses of mechanically ventilated sCAP patients with low IgM levels and elevated CRP levels, a trend in absolute mortality reduction from 36.6% to 11.8% (relative mortality reduction of 68%) could be observed. Because mortality for sCAP patients is still very high, the observed trend was especially relevant and encouraging to start preparing the phase IIII study.