GL03

Lipoarabinomannan (LAM) is a major antigen of Mycobacterium tuberculosis (MTB). Otsuka Company Ltd identified monoclonal antibodies binding to epitopes unique in LAM from MTB.  An enzyme-linked immunosorbent assay (LAM-ELISA) was developed to quantitate LAM. The ability of LAM-ELISA to measure concentrations of LAM in sputum as a biomarker of bacterial load prior to and during treatment in pulmonary tuberculosis has been assessed in 4 studies using clinical sputum samples. A recent analysis across all 4 studies focussed on the potential of LAM-ELISA to be a “real-time” pharmacodynamic (PD) biomarker. The analyses performed included the relationships between sputum LAM and bacterial burden measured by colony-forming units (CFU) from solid medium, time-to-detection (TTD) from Mycobacteria Growth Incubator Tube (MGIT)-culture and in addition the performance of LAM-ELISA  as a predictor of CFU and MIGIT-based culture positivity.  Sputum LAM concentration is correlated with bacterial burden in the sputum as measured by solid and liquid media and reflect changes in bacterial burden in response to TB treatment. As a ‘real-time’ PD biomarker LAM sputum may improve and accelerate decisions in TB trials, particular in interim analyses, adaptive trials or seamless trails enrolment.