Abstract No. 617 Lusutrombopag reliably increases platelets regardless of baseline platelet counts in thrombocytopenic chronic liver disease patients undergoing planned invasive procedures: results of two phase 3 trials

Lusutrombopag is an oral, small molecule thrombopoietin receptor agonist approved in Japan and US for treatment of thrombocytopenia (TCP), and in EU for severe TCP, associated with chronic liver disease (CLD) in patients undergoing planned invasive procedures. The degree of TCP may impact treatment response to lusutrombopag and the need for platelet transfusion (PT). This analysis evaluates the increase in platelet count (PC) and maximum PC achieved according to baseline PC. L-PLUS 1 (JapicCTI-132323) and L-PLUS 2 (NCT02389621) were two similar Phase 3 multicenter, randomized, double-blind, placebo-controlled studies; L-PLUS 1 (n = 97) was conducted in Japan and L-PLUS 2 (n = 215) was conducted globally. Patients with TCP due to CLD received lusutrombopag 3 mg or placebo for up to 7 days prior to an invasive procedure planned 9-14 days after randomization. Patients were adults with PC (x109/L) <50 at baseline. PT was mandated if PC remained <50 no more than 2 days prior to the planned invasive procedure. The change in PC over time was a key efficacy endpoint. A per-protocol (PP) population from the two trials was integrated for this analysis; PC values post-PT were excluded from the analysis when calculating the proportion of patients who met a criterion and summary statistics for maximum PC. 312 patients were randomized. Of 270 patients in the PP population, 78.1% of patients in the lusutrombopag group (n = 137) achieved a PC ≥50 at least once during the study versus 30.1% of patients in the placebo group (n = 133). PC increased by double or more in 47.4% and 3.8% in the lusutrombopag and placebo groups, respectively, and increased by ≥50% in 77.4% and 12.8%, respectively. In the lusutrombopag group, the average maximum PC stratified according to baseline PC of <20, ≥20-<30, ≥30-<35, ≥35-<40, and ≥40-<50 was 56, 45, 64, 82, and 87, respectively; conversely, the average maximum change in PC across baseline PC was +41, 21, 32, 45, and 42, respectively. Patients on lusutrombopag experienced a clinically meaningful response in PC regardless of whether the baseline PC was above or below 35.