Robert S. Brown, Jr., MD, MPH, FACG1, Namiki Izumi, MD, PhD2, Takeshi Kano, MS3, Toshimitsu Ochiai, PhD4, Masayuki Kurosaki, MD2, Francesco Violi, MD5, Pomy Shrestha, MD6
1Weill Cornell Medical College, New York, NY; 2Musashino Red Cross Hospital, Tokyo, Tokyo, Japan; 3Shionogi & Co., Ltd., Osaka, Osaka, Japan; 4Biostatistics Center, Shionogi & Co., Ltd., Osaka, Osaka, Japan; 5Sapienza Universita di Roma, Rome, Lazio, Italy; 6Shionogi Inc., Florham Park, NJ
Introduction: Lusutrombopag is a thrombopoietin receptor agonist (TPO-RA) approved in Japan (2015) and the US (2018) for treatment of thrombocytopenia (TCP), and in the EU (2019) for severe TCP, associated with chronic liver disease (CLD) in patients undergoing a planned invasive procedure. In an integrated analysis of two Phase 3 studies, lusutrombopag reduced the need for platelet transfusions compared to placebo. Treatment with TPO-RAs has been associated with an increased risk of thrombotic events in patients with CLD; thus, a thorough safety assessment of new agents is critical. A pooled retrospective analysis of 3 clinical studies was performed to assess safety of lusutrombopag.
Methods: Safety data from 3 double-blind, randomized, placebo-controlled studies in patients with CLD and TCP undergoing a planned invasive procedure (Phase 2b: M0626 [Japan; JapicCTI-121944], Phase 3: L-PLUS 1 [Japan; JapicCTI-132323] and L-PLUS 2 [global; NCT02389621]) were pooled. Adults with platelet counts < 50x109/L at baseline received lusutrombopag 3 mg or placebo for up to 7 days before a procedure planned 9-14 days after randomization. Platelet transfusion was given if the platelet count remained < 50x109/L no more than 2 days prior to procedure. Adverse event (AE) data were collected from signing of informed consent until the end of the post-treatment period or early termination.
Results: The pooled safety population included 341 patients (n=171, lusutrombopag; n=170, placebo). Approximately 65% of patients in the lusutrombopag and placebo groups experienced an AE (Table). Thrombotic and thromboembolic AEs occurred in 1.8% (3/171) of lusutrombopag patients (cardiac ventricular thrombosis, n=1 [patient had prior history of cardiac ventricular thrombosis]; portal vein thrombosis, n=2) and 2.4% (4/170) of placebo patients (mesenteric vein thrombosis, n=2; portal vein thrombosis, n=2). Overall, bleeding-related AEs occurred in less lusutrombopag vs placebo patients (15 [8.8%] vs 27 [15.9%]), respectively. The 3 AEs leading to death among patients taking lusutrombopag were not considered treatment-related but due to the progression of underlying disease.
Discussion: In this pooled safety analysis, lusutrombopag was safe and well-tolerated in patients with TCP and CLD undergoing planned invasive procedures. Approximately 50% fewer bleeding-related AEs and no increased risk of thrombotic and thromboembolic AEs were observed in patients treated with lusutrombopag vs placebo.
Citation: Robert S. Brown, Jr., MD, MPH, FACG; Namiki Izumi, MD, PhD; Takeshi Kano, MS; Toshimitsu Ochiai, PhD; Masayuki Kurosaki, MD; Francesco Violi, MD; Pomy Shrestha, MD. P1523 - LUSUTROMBOPAG IS A SAFE TREATMENT OPTION FOR THROMBOCYTOPENIA IN PATIENTS WITH CHRONIC LIVER DISEASE UNDERGOING A SCHEDULED INVASIVE PROCEDURE: POOLED SAFETY ANALYSIS FROM 3 STUDIES. Program No. P1523. ACG 2019 Annual Scientific Meeting Abstracts. San Antonio, Texas: American College of Gastroenterology.