Development pipeline

Trimodulin (BT-588, IgM Concentrate)

In the field of intensive care medicine Biotest is developing trimodulin, which is being investigated for the treatment of patients with severe community acquired pneumonia (sCAP). In sCAP patients suffer from very severe pneumonia, and a high number need life saving measures such as mechanical ventilation. The average mortality rate is between 30% and 50%, which makes sCAP one of the main causes of death in Europe and the USA. Besides pneumonia these patients usually suffer from other co-morbidities that come with the older age of the typical patient. Currently, the standard therapy is antibiotic therapy and intensive care treatment. Despite modern treatment algorithms mortality is still high in these patients.  Here, we and experts are convinced that an adjunctive therapy is necessary. For that reason adjunctive therapy with trimodulin is investigated in ventilated sCAP patients as a possibility of offering a better prognosis/outcome.

Trimodulin (BT-588, predecessor BT-086) is a human plasma-derived native polyclonal antibody preparation for intravenous administration. Trimodulin contains immunoglobulins IgM (~23%), IgA (~ 21%) and IgG (~56%). Trimodulin mediates its mode of action via three potential mechanisms which are;  opsonization of causal pathogens, neutralizing of microbial pathogens and their virulence factors (endo and exo toxins) and targeting the host inflammatory response (anti-inflammatory properties). These mechanisms are mediated by the binding and immunomodulatory capacities of each of the tri-component immunoglobulin preparation and were demonstrated in in-vitro systems. It is assumed that trimodulin acts through a range of mechanisms which are expected to counteract the pathophysiological processes which can otherwise lead to severe respiratory illness, sepsis or septic shock with multi organ failure and death. Successful patient treatment by combined binding of sCAP-related pathogens is an important part of the depicted potential mode of action.   

In the finalized clinical phase II study (CIGMA study), the efficacy and safety of trimodulin as an adjunctive therapy to standard of care in patients with sCAP versus standard of care (placebo) could be demonstrated. Each of the 160 patients included in the study needed treatment in an intensive care unit and was mechanically ventilated.

Although, the study missed its primary endpoint, reduction of ventilator free days, it delivered major new insights. An additional planned data analysis identified a patient subgroup who benefit greatly from trimodulin adjunctive therapy. In most of the study participants low IgM levels and elevated CRP levels could be observed. In patients with those specific characteristics absolute mortality was decreased from 36.6% (placebo) to 11.8%. This relates to a relative mortality reduction of 68%.

A phase III study with trimodulin in the above described patient group is currently planned.

Press releases

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
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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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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) Healthy volunteers 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