A Prospective Open-Label, Single-Arm Study to Evaluate the Efficacy and Safety of Lusutrombopag in Chinese Adults with Persistent or Chronic Primary Immune Thrombocytopenia

Background: Primary immune thrombocytopenia (ITP) is a life-threatening acquired autoimmune disorder characterized by decreased platelet counts (PLTs) and bleeding symptoms. Current international and Chinese guidelines preferably suggest use of thrombopoietin receptor agonists (TPO-RAs) among several others for second-line treatment of ITP (Neunert C et al, 2019). TPO-RAs (romiplostim, eltrombopag, hetrombopag, and avatrombopag) has been approved for treating ITP in Chinese. Lusutrombopag is a newly approved TPO-RA with the absence of clinically significant hepatotoxicity, interactions between drugs and restrictions on food (Katsube T et al, 2019; Katsube T et al, 2020) for the treatment of thrombocytopenia associated with chronic liver disease in adults in China in June 2023. However, platelet count responses to lusutrombopag in treating ITP has not been previously reported. To explore the safety and efficacy of lusutrombopag in Chinese patients with persistent or chronic primary ITP, we conducted this study.

Methods： This is a prospective, single-center, single-arm, open-label study .The critical inclusion criteria were subjects aged ≥18 years; diagnosed with persistent or chronic ITP (≥3 months ) and had previously received one or more ITP therapies; PLT <30×10 or <50×10^9/L if receiving stable steroids at enrollment, etc. The study consisted of three parts: screening (2 weeks), core study (patients were treated with a stable dose of once-daily 3mg lusutrombopag for up to 4 weeks ) and titration study (patients were treated with lusutrombopag titrated to a maximum dose of 6mg daily or a minimum of 3mg weekly according to their PLTs for 8 weeks).The primary endpoint was percentage of patients with a platelet response after 4 weeks (defined as PLT ≥50x10^9/L after 4 weeks of lusutrombopag on Day 29 or prematurely ≥250x10^9/L prior to Day 29). Key secondary endpoints included platelet responses after Week 12, time to first achieve a PLT of ≥50x10^9/L, durable responses, reduction in the use of concomitant ITP medications and adverse events (AEs), etc. This trial was registered with ClinicalTrials.gov (NCT06287567).

Results: This study aims to enroll 17 eligible patients. From April 17 to July 24, 2024, 10 eligible subjects were enrolled. One dropped out at Week 6, and nine are ongoing. Among the 10 patients, median duration of treatment with the study drug was 5 weeks (range 0.3 -11). The mean age of the 10 patients at enrollment was 53 years (range 27-67) with 60% of them female. The median weight was 79kg (range 55-100). The median time since ITP diagnosis was 8 months (range 4-60). None had a history of splenectomy. Prior to enrollment, 50% had been receiving stable steroids (same milligram amount ±10% and ≤ 20mg of equivalent dose of prednisone) for ≥2 weeks and no other concomitant medications affecting PLTs were administered. This abstract only describes platelet responses of the eight patients who have finished the 4-week core study, as two of the 10 subjects were enrolled on July 22, 2024 and PLTs after first dosing of lusutrombopag can't be obtained until July 29. The median PLT of the eight patients before treatment was 19×10^9/L (range 3-40×10^9/L). Of the eight patients 100.0% achieved a PLT ≥50×10^9/L within 4 weeks after the first dose of lusutrombopag with seven (87.5%) remaining ≥50×10^9/L after 4 weeks. The median PLT from Week 1 to 4 was 107×10^9/L (range 42-338×10^9/L) ,195×10^9/L (range 58-373×10^9/L), 118×10^9/L (range 16-184×10^9/L) and 89×10^9/L (range 44-232×10^9/L) respectively. Three patients（37.5%）experienced a PLT ≥250×10^9/L in the core study with a maximum PLT of 373×10^9/L and stopped treatment until PLT≤100×10^9/L. The median time to response was 1-week (range 1-2), and six (75%) achieved a PLT ≥50×10^9/L and four (50%) achieved ≥100×10^9/L respectively after 1 week of treatment while eight (100%) patients all achieved a PLT ≥50×10^9/L after 2 weeks of treatment. During the core study, seven (87.5%) achieved a durable platelet response defining as PLTs ≥50×10^9/L in 75% of weeks. Treatment emergent adverse events (TEAEs) occurred in four of eight patients and there were no treatment-related adverse reactions. None experienced serious adverse events (SAE).

Conclusions: Lusutrombopag, a newly approved TPO-RA in China, has shown preliminary efficacy initiated with a once-daily 3mg tablet with tolerability in Chinese adults with persistent or chronic primary ITP.

No relevant conflicts of interest to declare.

This study is to exploratorily investigate the efficacy and safety of the study drug-lusutrombopag in treating primary immune thrombocytopenia (ITP) in Chinese adults. It's originally indicated for the treatment of thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure. The reason for conducting this off-label study is based on its potential efficacy in treating primary ITP.