PF697 LUSUTROMBOPAG IS A SAFE AND EFFICACIOUS TREATMENT OPTION FOR THROMBOCYTOPENIA IN PATIENTS WITH CHRONIC LIVER DISEASE UNDERGOING PLANNED INVASIVE PROCEDURES: INTEGRATED ANALYSIS OF TWO PHASE 3 TRIALS
Authors: R.S. Brown, M. Imawari, N. Izumi, Y. Osaki, T. Ochiai, T. Kano, R. Bentley, M. Peck‐Radosavljevic
Journal: HemaSphere (2019)

Background: Lusutrombopag is an oral, small molecule thrombopoietin receptor agonist approved in Japan and US for improvement of thrombocytopenia, and in EU for severe thrombocytopenia, associated with chronic liver disease in patients undergoing planned invasive procedures. Aims: An integrated analysis was performed to assess the consistency of the efficacy and safety of lusutrombopag clinical trial data across a larger population. Methods: L‐PLUS 1 (Japan; JapicCTI‐132323) and L‐PLUS 2 (global; NCT02389621) were 2 similar Phase 3 multicenter, randomized, double‐blind, placebo‐controlled studies. Adults with thrombocytopenia associated with chronic liver disease and platelet counts (x10 9 /L) &lt;50 at baseline received lusutrombopag 3 mg or placebo for up to 7 days prior to an invasive procedure scheduled 9–14 days after randomization. Platelet transfusion was mandated if the platelet count remained &lt;50 no more than 2 days prior to procedure. The efficacy endpoint for the integrated analysis was the proportion of patients who required no platelet transfusion prior to the invasive procedure and no rescue therapy for bleeding from randomization through 7 days after the invasive procedure. Another key efficacy endpoint was duration of the increase in platelet count (≥50). Results: A total of 312 patients were randomized in the 2 studies. In the intent‐to‐treat and per‐protocol populations, 68.2% and 73.7% of patients randomized to lusutrombopag avoided the need for platelet transfusion vs 23.9% and 17.3% of patients randomized to placebo for a difference of proportion of 44.4% and 55.8% ( P &lt; 0.0001), respectively ( Figure ). Platelet counts remained ≥50 for a median of 20.9 days in the lusutrombopag group for patients not requiring a platelet transfusion, compared to 0.3 days for patients requiring a platelet transfusion in the placebo group. Three patients experienced treatment‐related thrombotic or thromboembolic adverse events; 2 with lusutrombopag (portal vein thrombosis and cardiac ventricular thrombosis; maximum platelet counts were 79 and 119, respectively) and 1 with placebo (portal vein thrombosis; maximum platelet count = 167). The proportion of patients experiencing ≥1 adverse event were similar in the lusutrombopag (61.9%) and placebo groups (64.5%); of these, 6.5% and 9.0% events, respectively, were deemed treatment‐related. Summary/Conclusion: Lusutrombopag demonstrated efficacy and safety in the pooled analysis. Lusutrombopag was superior to placebo as treatment for thrombocytopenia associated with chronic liver disease in patients undergoing planned invasive procedures; statistically significantly more patients avoided platelet transfusion with lusutrombopag treatment. Patients maintained platelet counts ≥50 for almost 3 weeks. Lusutrombopag had a similar safety profile to placebo. image