Development pipeline

Trimodulin (BT-588, IgM Concentrate)

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.

Press releases

IgM Concentrate: Remarkable relative reduction in morta...

16.03.2016,

IgM Concentrate: Remarkable relative reduction in mortality of more than 50% in subgroup of patients- Favourable new data of phase II trial with IgM Concentrate in patients with severe Community Acqui ... [More]

Biotest's IgM Concentrate shows encouraging results in ...

30.06.2015,

Biotest's IgM Concentrate shows encouraging results in life-threatening pneumonia - Phase II trial with IgM Concentrate completed in patients with severe community acquired pneumonia (sCAP) requiring ... [More]

Publications

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Schmiedl et al.: Safety of the IgM enriched immunoglobulin concentrate BT086 in healthy volunteers – results of a dose-escalating single dose phase I study. Br J Clin Pharmacol 2011, 72:1-46. Abstract 40
[ Link ]

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Schmiedl et al.: Evaluation of pharmacokinetics and safety of the IgM enriched immunoglobulin concentrate BT086 in healthy volunteers - results of a multiple dose phase I study. Br J Clin Pharmacol 2011, 72:1-46. Abstract 43
[ Link ]

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Welte et al.: Concept for a study design in patients with severe community-acquired pneumonia: A randomised controlled trial with a novel IGM-enriched immunoglobulin preparation – The CIGMA study. Respiratory Medicine , Volume 109 , Issue 6 , 758 - 767
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Welte et al., Intensive Care Med. 2018 Apr;44(4):438-448. doi: 10.1007/s00134-018-5143-7. Epub 2018 Apr 9. Efficacy and safety of trimodulin, a novel polyclonal antibody preparation, in patients with severe community-acquired pneumonia: a randomized, placebo-controlled, double-blind, multicenter, phase II trial (CIGMA study).
[ Link ]

Clinical trials

Title

Indication

Status

 
Trimodulin (Study 982) Severe community acquired pneumonia Study completed

A Randomized, Double-blind, Placebo-controlled, Multicenter, Parallel-group, Adaptive Group-sequential Phase II Study, to Determine the Efficacy and Safety of BT086 as an Adjunctive Treatment in Severe Community Acquired Pneumonia (sCAP)

Link clinicaltrials.gov
 
IgM Concentrate (Study 970) Severe community acquired pneumonia Study completed

A prospective, randomised, placebo-controlled, and single-blind phase I study investigating safety, tolerability, and pharmacokinetic properties of IgM Concentrate BT086 in healthy subjects