Safety Of Avatrombopag Research Articles

Efficacy and Safety of Avatrombopag in Combination with Standard Immunosuppressive Therapy for Severe Aplastic Anemia

Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disease. The addition of eltrombopag to immunosuppressive therapy (IST) improves the response rate and response quality of SAAs, but its hepatotoxicity is concerning. Avatrombopag (AVA), another small-molecule thrombopoietin receptor agonist without hepatotoxicity, has unknown efficacy in SAA treatment. This retrospective study aimed to assess the efficacy and safety of AVA, a small-molecule thrombopoietin receptor agonist, when added to IST in SAA patients. A total of 42 patients treated with IST and AVA were compared to a historical cohort of 84 patients receiving IST alone, utilizing propensity score matching. The median age was 31.5 (6.0-67.0) years old in Group A and 26 (16.0-45.0) years old in Group B. At 3 months, Group A showed higher complete response (CR) and overall response (OR) rates than Group B (CR: 19.0% vs. 4.8%, P = 0.024; OR: 54.8% vs. 39.3%, P=0.145). Higher CR and OR rates were also found at 6 months in Group A than in Group B (CR 31.0% vs. 14.3%, P=0.145; OR 71.4% vs. 51.2%, P=0.048). In multivariate analysis of Group A, a shorter interval from disease onset to anti-thymocyte globulin (ATG) treatment (≤6 months) (P=0.005) predicted better responses rate at 6 months. Event free survival was also improved in Group A (60.7% vs. 49.6%). AVA was well-tolerated, with no hepatic injury observed during treatment, even in those with pre-existing hepatic impairment. The addition of AVA to IST improves both the response rate and response quality in SAA patients while ensuring safety.

Real-world evidence of avatrombopag for the treatment of immune thrombocytopenia intolerant or ineffective to eltrombopag/hetrombopag.

Due to the limited real-world research on the application of avatrombopag (AVA) for immune thrombocytopenia (ITP) in China, we evaluated the effectiveness and safety of AVA in clinical practice. We included 121 adult ITP patients treated with AVA across three medical centres. Based on the reasons for choosing AVA, these patients were divided into eltrombopag (ELT)/hetrombopag (HET) intolerance group (IG), and ELT/HET unresponsive group (UG). Compared with UG, more patients in IG had a history of liver disease and received fewer treatments before AVA. Amongst all patients, 83% had platelet response (≥30 × 109/L) after AVA and 62% achieved complete response (≥100 × 109/L, CR). Sixty-two percent in IG and 56% in UG were able to discontinue more than one concomitant ITP medication. A total of 17 patients underwent multiple switches of thrombopoietin receptor agonists (TPO-RAs), resulting in an 88% platelet response rate. Sixty-three patients discontinued AVA, 27% were due to unaffordability. AVA was well tolerated in most patients. In the ITP population, AVA proved effective and safe, particularly in patients intolerant or unresponsive to ELT/HET. Patients benefited from TPO-RAs switches, particularly those undergoing multiple switches. However, many patients struggled with the long-term financial burden of AVA.

Efficacy and safety of avatrombopag in the treatment of thrombocytopenia after umbilical cord blood transplantation.

Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We conducted a retrospective study to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation. Fifty-two patients were given AVA within 30days post-UCBT, and the treatment was continued for more than 7days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5days vs. 38.0days, Z=2.095, P=0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs. 84.5% vs. 80.6%, P<0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P=0.104). Patients who initiated AVA treatment within 14days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14days post-UCBT (96.6% vs. 73.9%, P=0.003). In summary, compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14days post-UCBT).

Efficacy and safety of avatrombopag in aplastic anemia patients with liver disease.

Abstract Background and Objectives Hyperglycemia is associated with adverse outcomes in patients with acute myocardial infarction (AMI) as well as in patients with heart failure. However, the significance of admission glycemic variability (GV) in predicting outcomes among diabetes patients with heart failure (HF) following acute ST-segment elevation myocardial infarction (ASTEMI) remains unclear. This study aims to explore the prognostic value of admission GV and admission glycosylated hemoglobin (HbA1c) levels in individuals diagnosed with type 2 diabetes and HF following ASTEMI. Methods We measured GV and HbA1c upon admission in 484 consecutive patients diagnosed with type 2 diabetes and HF following ASTEMI. GV, indicated as the mean amplitude of glycemic excursions (MAGE), was assessed utilizing a continuous glucose monitoring system (CGMS). admission MAGE values were categorized as &lt; 3.9 or ≥ 3.9 mmol/L, while HbA1c levels were classified as &lt; 6.5 or ≥ 6.5%. Participants were followed up prospectively for 12 months. The relationship of admission MAGE and HbA1c to the major adverse cardiac event (MACE) of patients with type 2 diabetes and HF following ASTEMI was analyzed. Results Among the 484 enrolled patients, the occurrence of MACE differed significantly based on MAGE categories (&lt; 3.9 vs. ≥ 3.9 mmol/L), with rates of 13.6% and 25.3%, respectively (P = 0.001). While MACE rates varied by HbA1c categories (&lt; 6.5 vs. ≥ 6.5%) at 15.7% and 21.8%, respectively (P = 0.086). Patients with higher MAGE levels exhibited a notably elevated risk of cardiac mortality and an increased incidence of HF rehospitalization. The Kaplan-Meier curves analysis demonstrated a significantly lower event-free survival rate in the high MAGE level group compared to the low MAGE level group (log-rank test, P &lt; 0.001), while HbA1c did not exhibit a similar distinction. In multivariate analysis, high MAGE level was significantly associated with incidence of MACE (hazard ratio 3.645, 95% CI 1.287–10.325, P = 0.015), whereas HbA1c did not demonstrate a comparable association (hazard ratio 1.075, 95% CI 0.907-1.274, P = 0.403). Conclusions Elevated admission GV emerges as a more significant predictor of 1-year MACE in patients with type 2 diabetes and HF following ASTEMI, surpassing the predictive value of HbA1c.

Efficacy and safety of avatrombopag in Chinese children with persistent and chronic primary immune thrombocytopenia: A multicentre observational retrospective study in China.

Avatrombopag (AVA) is a novel thrombopoietin receptor agonist (TPO-RA) that has been recently approved as a second-line therapy for immune thrombocytopenia (ITP) in adults; however, its safety and efficacy data in children are lacking. Here, we demonstrated the efficacy and safety of AVA as second-line therapy in children with ITP. A multicentre, retrospective, observational study was conducted in children with persistent or chronic ITP who did not respond to or relapsed from previous treatment and were treated with AVA for at least 12 weeks between August 2020 and December 2022. The outcomes were the responses (defined as achieving a platelet count ≥30 × 109/L, twofold increase in platelet count from baseline and absence of bleeding), including rapid response within 4 weeks, sustained response at weeks 12 and 24, bleeding control and adverse events (AEs). Thirty-four (18 males) patients with a mean age of 6.3 (range: 1.9-15.3) years were enrolled. The median number of previous treatment types was four (range: 1-6), and 41.2% patients switched from other TPO-RAs. Within 4 weeks, overall response (OR) was achieved in 79.4% patients and complete response (CR, defined as a platelet count ≥100 × 109/L and the absence of bleeding) in 67.7% patients with a median response time of 7 (range: 1-27) days. At 12 weeks, OR was achieved in 88.2%, CR in 76.5% and sustained response in 44% of patients. At 24 weeks, 22/34 (64.7%) patients who achieved a response and were followed up for 24 weeks were evaluated; 12/22 (54.55%) achieved a sustained response. During AVA therapy, median platelet counts increased by week 1 and were maintained throughout the treatment period. The proportion of patients with grade 1-3 bleeding decreased from 52.95% at baseline to 2.94% at 12 weeks, while concomitant ITP medications decreased from 36.47% at baseline to 8.82% at 12 weeks, with only 9 (26.47%) patients receiving rescue therapy 23 times within 12 weeks. There were 61.8% patients with 59 AEs: 29.8% with Common Terminology Criteria for Adverse Events grade 1 and the rest with grade 2. These findings show that AVA could achieve a rapid and sustained response in children with persistent or chronic ITP as a second-line treatment, with good clinical bleeding control and reduction of concomitant ITP therapy, without significant AEs.

Efficacy and safety of avatrombopag in combination with immunosuppressive therapy in treatment-naïve and relapsed/refractory severe aplastic anaemia: protocol for the DIAAMOND-Ava-FIRST and DIAAMOND-Ava-NEXT Bayesian Optimal Phase II trials

IntroductionImmunosuppressive therapy (IST) with antithymocyte globulin (ATG) and ciclosporin is standard of care for patients with severe aplastic anaemia (sAA) not eligible or suitable for allogeneic stem cell transplant. While...

Efficacy and Safety of Avatrombopag in the Treatment of Chemotherapy-Induced Thrombocytopenia Refractory to Rhtpo in Patients with Lymphoma

Background: Chemotherapy-induced thrombocytopenia (CIT) is a common cause of chemotherapy dose reductions and treatment delays. With applications of recombinant human interleukin 11 (rhIL-11) and recombinant human thrombopoietin (rhTPO), outcomes of patients with CIT have improved significantly. however，some patients with severe thrombocytopenia still have poor responses to the above therapies. Avatrombopag is an orally administered thrombopoietin receptor agonist and can stimulate thrombopoiesis in haematopoietic stem cells. Avatrombopag has been approved in the USA, Europe, and China for thrombocytopenia in patients with chronic liver disease who are scheduled to undergo a surgery. It also has been approved for patients with chronic immune thrombocytopenia who are unresponsive to previous treatments in the USA and Europe. The aim of this study is to evaluate the efficacy and safety of avatrombopag in the treatment of refractory CIT. Methods: The clinical data of 23 lymphoma patients with grade 3/4 CIT unresponsive to rhTPO treatment for 7-10 days were collected from April 2022 to May 2023. All patients received avatrombopag orally at a dose of 40 to 60 mg / day combined with subcutaneous injection of rhTPO (300 U/kg/day). Response (R) was defined as a platelet count≥ 50 × /L, or doubling of the baseline platelet count, and absence of bleeding. Platelet transfusion was allowed when the platelet count was less than 10×109/L or with bleeding events. When the platelet count recovered to ≥100 ×10 9/L or increased 50 ×10 9/L from baseline, treatments of avatrombopag and rhTPO were stopped. Results: The median age of the 23 patients with refractory CIT was 57 (range 17‒83) years. The pathological subtypes were diffuse large B cell lymphoma (DLBCL) (n=10), Burkitt lymphoma (n=4), angioimmunoblastic T-cell lymphoma (AITL) (n=3), follicular lymphoma (FL) (n=2), extranodal NK/T cell lymphoma (ENKTL) (n=1), anaplastic large cell lymphoma (ALCL) (n=1), B-lymphoblastic lymphoma (n=1), and mantle cell lymphoma (MCL) (n=1). The treatment consisted of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) (n=11), Hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone), high-dose methotrexate with cytarabine (n=6), liposomal mitoxantrone-containing regimen (n=4), bendamustine-containing regimen (n=1), and peg-asparaginase-based regimens (n=1). At baseline, 19 patients experienced grade 3 and 4 patients experienced grade 4 thrombocytopenia after chemotherapy. The median lowest platelet level was 12×10 9/L (range 2‒44×10 9/L). Two patients developed grade 1 bleeding events and one patient occurred grade 2 bleeding events. Nineteen patients received platelet transfusion. After receiving the combination therapy of avatrombopag, 73.9% (17/23)of patients achieved the primary end point of corrected platelet counts (≥50×10 9/L )and were free from platelet transfusion. The median time to response was 11 (range 5‒25) days. No treatment-related adverse events such as elevated aminotransferases, thrombosis, fatigue, fever and dizziness were noticed during administration. Two patients received avatrombopag as secondary prophylactic treatment, and there were no grade 4 thrombocytopenia or bleeding events during subsequent cycles of chemotherapy. Conclusion: Avatrombopag is effective and safe in the management of CIT for lymphoma and it can be used as an alternative / combination treatment for the patients who refractory to rhTPO. The further clinical research is still needed to confirm this conclusion.

Efficacy and Safety of Avatrombopag in the Treatment of Chemotherapy-Induced Thrombocytopenia in Children with Acute Lymphoblastic Leukemia: A Retrospective Study

Introduction: Chemotherapy-induced thrombocytopenia (CIT) is one of the most common complications during cancer treatment, increasing the risk of bleeding, medical costs, and potentially affecting treatment outcomes by necessitating chemotherapy dose reductions or delays. Avatrombopag, a thrombopoietin receptor agonist, has been approved as the first-line drug for the treatment of thrombocytopenia in chronic liver diseases. Its efficacy and safety was demonstrated in disorders like aplastic anemia and primary immune thrombocytopenia. However, the research regarding its use in children with CIT is lack. Objective: This retrospective study aimed to analyze the efficacy and safety of avatrombopag in the treatment of chemotherapy-induced thrombocytopenia in children with acute lymphoblastic leukemia, providing a potential new therapeutic option for managing CIT in pediatric cancer patients. Methods: The data of experimental group were collected from 30 pediatric patients with acute lymphoblastic leukemia and CIT who received avatrombopag treatment in the pediatric ward of Southern Hospital from August 2022 to July 2023. Additional data from 250 pediatric patients with acute lymphoblastic leukemia and CIT who did not receive avatrombopag treatment at Southern Hospital from January 2020 to July 2023 were collected as the control group. A propensity score matching method was employed to analyze the two patient groups, resulting in a successful matching of 30 pairs (CAT 21 pairs, CAT+9 pairs). The collected clinical data included age, gender, height, weight, risk stratification, infection status, platelet count changes during each chemotherapy cycle, platelet transfusion frequency, clinical manifestations of bleeding, avatrombopag usage, and complications. All patients were treated with the 2020-CCCG-ALL chemotherapy regimen,diagnosed with CIT,under 18 years of age, and excluded if they had concomitant hematological disorders, chronic liver disease, cardiovascular diseases, severe arterial or venous thrombosis, or splenomegaly. The initial avatrombopag dose was 10mg daily for patients weighing less than 30kg and 20mg daily for patients weighing 30kg or more. Avatrombopag was stopped when PLT≥100×10 9/L or an increase in PLT by ≥50×10 9/L compared to pre-treatment levels. Results: Comparison between the experimental and control groups revealed that the experimental group had a shorter duration of grade 3 or higher thrombocytopenia (3.36±1.77 days vs. 4.7±2.46 days, P=0.019) and a shorter time to platelet recovery (7.9±2.63 days vs. 9.76±2.77 days, P=0.01). Subgroup analysis within the CAT and CAT+ chemotherapy phases indicated that significant platelet value differences (P&amp;lt;0.05) were observed between the two groups at the start of platelet decline (day 10±2) [PLT: (268.13±216.52) ×10 9/L vs. (152.13±89.58) ×10 9/L] and during platelet nadir (day 14±2) [PLT: (435.97±285.83) ×10 9/L vs. (285.07±148.67) ×10 9/L]. Additionally, a statistically significant difference (P&amp;lt;0.05) in PLT change from baseline to day 5 and day 7 was observed in the experimental group [46.5 (20.5, 93) ×10 9/L and 67 (15.5, 180) ×10 9/L, respectively]. During the chemotherapy cycles, only 4 patients (8.3%) experienced bleeding events, and after avatrombopag treatment, 11 patients (22.9%) did not require platelet transfusions. Four adverse events of secondary platelet increase were recorded, and no other adverse events were reported. Conclusion: Avatrombopag, as an alternative treatment for chemotherapy-induced thrombocytopenia in children with acute lymphoblastic leukemia, demonstrated the potential to promote platelet recovery and exhibited good safety. keywords:avatrombopag,Chemotherapy-induced thrombocytopenia,acute lymphoblastic leukemia

Real-World Evidence of Avatrombopag for the Treatment of Immune Thrombocytopenia Intolerant or Ineffective to Eltrombopag/Hetrombopag

Abstract Objectives: Thrombopoietin receptor agonists (TPO-RA) have dramatically changed the treatment landscape for immune thrombocytopenia (ITP). Although avatrombopag has been confirmed to achieve platelet response for chronic ITP in clinical trials, and it has no hepatotoxicity unlike eltrombopag or hetrombopag, there is still a lack of real-world research on the application of avatrombopag in Chinese ITP patients. Here, we aimed to evaluate the effect and safety of avatrombopag in ITP treatment in a real-world clinical practice. Methods: In this retrospective analysis, we enrolled consecutive cohorts of 50 adult ITP patients who received avatrombopag in two centers from January 2021 to March 2023. The median duration of follow-up of these patients was 16.5 months (range from 3.8 to 25.4 months). Results: The median age of patients was 44 years when they received the treatment of avatrombopag, and 42% of them were males. Most patients (n=45) had a persistent (3-12 months) or chronic course (more than 12 months) of ITP. The patients in our study were heavily treated, who received a median of 4 kinds of ITP treatment prior to avatrombopag. The baseline TPO levels was 88.1 (110.2±84.5) pg/ml. Based on the reasons for choosing avatrombopag, these patients were divided into eltrombopag/hetrombopag intolerance group (IG, n=14) and eltrombopag/hetrombopag unresponsive group (UG, n=36). The reasons for choosing avatrombopag in IG included active hepatitis B (n=4), hepatic insufficiency before using TPO-RA (n= 6), autoimmune hepatitis (n=1), hepatic lesion after using eltrombopag (n=2), and myelofibrosis after using eltrombopag (n=1). Compared with UG, more patients had a history of liver disease (active Hepatitis B and autoimmune liver diseases, P=0.003). The median platelet count before avatrombopag was 9 × 10 9/L. The median duration of avatrombopag treatment was 12 weeks and the median weekly dose of avatrombopag was 140 mg. Among the total cohort, platelet response (platelet count ≥30 × 10 9 /L) was achieved in 44/50 (88%) and complete platelet response (platelet count ≥100 × 10 9 /L) was seen in 35/50 patients (70%) after using avatrombopag. The median time of platelets rising above 30 × 10 9 /L was 7 days, while it was 8 days when platelet count exceeded 50 × 10 9 /L. Nearly half patients (47%) were able to discontinue more than 1 concomitant ITP medication after avatrombopag treatment. Besides, most patients (74%) in our study tapered off or withdrew steroids. There were no significant differences in baseline platelet count, 30-day response rate, the maximum effective dose of avatrombopag and duration of avatrombopag between IG and UG. So far, 19 patients achieved platelet response were still taking avatrombopag, and 58% of them maintained platelet count above 100× 10 9 /L. Meanwhile, 31 patients discontinued avatrombopag.The reasons for withdrawal of drug included adverse events (n=2), sustained remission in ITP (n=8), no/lose response to avatrombopag (n=10), and unablity to afford the cost consistently (n=11). Avatrombopag was well tolerated in most patients, even those suffered from hepatic insufficiency and/or myelofibrosis after other TPO-RA. However, two cases had thrombosis and two patients reported mild fatigue. Conclusion: In the ITP population, avatrombopag was effective and safe, especially for those intolerant or ineffective to eltrombopag/hetrombopag. However, most patients with ITP were not able to afford the long-term usage of avatrombopag in China.

Interim Baseline Characteristics of Adult Patients with Immune Thrombocytopenia Enrolled in the Observational Multicenter Phase 4 Adopt Study to Evaluate the Use and Effectiveness of Avatrombopag

Background: Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by low platelet counts and increased bleeding rate. Current first-line ITP treatments include corticosteroids and immunoglobulins. If first-line therapy fails, subsequent treatment options include the thrombopoietin receptor agonists (TPO-RAs). Avatrombopag (AVA), the most recently approved TPO-RA, is a small molecule, administered orally with no food-type restrictions, and no significant hepatotoxicity. AVA was approved by FDA in 2019 and EMA in 2021, for the treatment of chronic ITP in adult patients who are refractory to other treatments. The Phase 4 ADOPT study (NCT04943042) will generate data on the real-world effectiveness and safety of AVA in routine clinical practice in Europe. Described here are the interim baseline characteristics of patients enrolled in the ADOPT study. Study objective and methods: ADOPT is a multicenter, observational study with the primary objective to describe the real-world effectiveness of AVA treatment over a prospective period of 12 months. Prospective data will be collected at routine clinical visits. In addition, retrospective data will be collected from patients' medical records for up to 12 months prior to AVA treatment start. Eligible patients must be ≥18 years of age, have provided informed consent, have an established and well documented ITP diagnosis, and are treated with, or initiating treatment with AVA for ITP, at enrollment. Exclusion criteria include enrollment in other clinical interventional studies, or intake of an investigational medicinal product, ≤3 months prior to inclusion. The primary endpoint is the cumulative number of weeks with a platelet count ≥30×10 9/L. Platelet counts during rescue medication use and within 4 weeks after stopping a rescue medication or following splenectomy are considered non-response and thus not included in the primary endpoint cumulative number. Secondary endpoints supporting the primary objective include cumulative number of weeks with a platelet count ≥50×10 9/L, patients (n [%]) with a platelet count ≥30×10 9/L and ≥50×10 9/L for at least 8 consecutive weeks, patients (n [%]) experiencing WHO bleeding grade ≥2, patients (n [%]) requiring rescue medication, and time from AVA treatment start to platelet count ≥30×10 9/L and ≥50×10 9/L. Additional secondary endpoints are AVA dose and dosing frequency, reason for ITP treatment discontinuation or change from one ITP treatment to another (prior to and during the study), use of concomitant ITP medications, physicians' satisfaction with outcome of AVA treatment (5-point scale), physician assessment of clinically meaningful effects (Clinical Global Impression of Change scale), healthcare resource use, as well as a number of patient reported outcomes (PROs). Secondary safety endpoints include serious adverse events and adverse events of special interest (thromboembolic events [TEEs] and significant bleeding events). Results: Fifty-six patients have been enrolled in the study as of July 2023, and demographic and baseline characteristics information were available for 39 patients (Table 1). The mean age (SD) was 52.2 (18.10) years and 20 patients were male (51.3%). Nine patients had a baseline PC &amp;lt;30x10 9/L. Eight patients (20.5%) reported newly diagnosed/persistent ITP with &amp;lt;12 months disease duration since diagnosis; 31 (79.5%) had chronic ITP. A majority of patients (n=22; 56.4%) had no previous exposure to TPO-RAs. One patient was splenectomized (2.6%), and seven had experienced prior TEEs (17.9%). Conclusions: This baseline interim data set from the ADOPT Phase 4 study provides important insight into the types of ITP patients who are being prescribed avatrombopag across European centers. More than half of enrolled patients were TPO-RA naïve, and over 20% did not have chronic ITP although the mean duration of ITP was 7.6 years and median duration of 4 years at the time of first AVA treatment. Though previous clinical trials excluded patients with newly diagnosed/persistent ITP and prior TEEs, this real-world evidence study does not exclude such patients. We look forward to presenting safety and efficacy data, as well as multiple PROs, from this observational study at future scientific meetings. Study status: The study was initiated in January 2022, will include approximately 60 sites in Europe, and enroll 150 patients in total.

Avatrombopag in Immune Thrombocytopenia (ITP). Real-Life Experience of Its Use in Hospitals within the Community of Madrid, Spain (AVAMAD STUDY)

Introduction Thrombopoietin receptor agonists (TPO-RAs) are recommended as second-line treatment for immune thrombocytopenia (ITP) according to the Spanish ITP group (GEPTI) guidelines. Avatrombopag (AVA) is an oral TPO-RA, recently launched in Spain, for which we have little data available beyond the pivotal trial. The main objectives of our study were to evaluate the efficacy and safety of AVA in patients with ITP. Methods In this observational, retrospective, multicenter study in 10 hospitals in the Community of Madrid, we have analyzed adult patients with ITP treated with AVA from July 2022-May 2023. Demographic characteristics, response, rescue therapy, adverse effects and treatment discontinuation were analyzed. The definition of ITP and response were those described by Provan et al. The study protocol was designed and applied in accordance with the principles of the Declaration of Helsinki. Statistical analysis was performed using IBM SPSS Statistics v28.0. Fisher and Mann-Whitney tests were used for bivariate analysis and Kaplan-Meier curves for response time. Results A total of 66 patients were included. The median age was 52 years old (IQR 34-71). Table 1 describes the general characteristics. There was a median of 2 (IQR1-3) previous lines of treatment before starting AVA. The reasons for its initiation were: refractoriness to previous treatment and/or corticodependence in 39% (25/66), loss of response in 34% (22/66), switch due to patient preference in 14% (9/66) and switch due to adverse effects with previous treatment in 5% (3/66). In 8% (5/66) there was more than one reason for change. The previous line of treatment is described in Table 1. The median platelet count at baseline was 36x10 9/L(IQR 13-61). With a median follow-up of 16 weeks (IQR 8-28), 86% of the pateints (57/66) were responders. 73% had complete response. 24% percent (16/66) required salvage therapy. In the bivariate analysis, 100% of those aged ≥65 years presented response vs. 75% in &amp;lt;65 years (p=0.003). A complete response was achieved in 88.6% of women versus 54.8% of men (p=0.002). Patients with complete response received fewer lines of treatment (1 [IQR 1-3] vs 3.5 [IQR 2-6]); p&amp;lt; 0.001). Complete response was achieved in 60.5% of patients who received previous treatment with eltrombopag (p=0.01), in 47.8% of those with romiplostim (p&amp;lt;0.001), in 40% with rituximab (p=0.02), in 33.3% with splenectomy (p=.0.01) and in 22.2% with fostamatinib (p=0.00).The median time from initiation of AVA to response was 2,1 weeks [IQR 2-4] (Figure 1). Twelve patients (18%) discontinued AVA due to: lack of response (n=6), adverse effects (n=3), one patient prior to scheduled surgery, and In these patients AVA was restarted with dose adjustment. Adverse effects are described in Table 1. Conclusions The results of the use of AVA in real-life demonstrated a high response rate, more favorable in the initial lines of treatment. In addition, it reduces the need for salvage therapy and has a low adverse effect profile. A larger number of patients and a longer follow-up are needed to verify these results and to answer some questions such as whether it is possible to discontinue AVA treatment after response and the percentage of patients with sustained response following AVA discontinuation.

Efficacy and Safety of Avatrombopag on Thrombocytopenia after Chemotherapy in Acute Leukaemia

Background: Thrombocytopenia following chemotherapy is a common and serious complication that leads to an increased risk of bleeding and poor prognosis for patients with acute leukaemia. Current therapeutic strategies consist of platelet transfusion, recombinant human interleukin-11(rhIL-11) and recombinant human thrombopoietin (rhTPO) injection, but these strategies are not satisfactory for some patients and the treatment remains challenging. Avatrombopag is a novel thrombopoietin receptor agonist, which had been approved for thrombocytopenia in patients with chronic liver disease who are scheduled to undergo a surgery in the USA, Europe, and China, and in patients with chronic immune thrombocytopenia who were unresponsive to previous treatments in the USA and Europe. This study aims to determine the efficacy and safety of avatrombopag on thrombocytopenia after chemotherapy of acute leukaemia, and to increase the evidence for clinical use of avatrombopag. Methods: The clinical data of 24 acute leukaemia patients with grade 3/4 chemotherapy-induced thrombocytopenia (CIT) for 3-28 days were collected from February 2022 to February 2023. All patients received avatrombopag orally at a dose of 40 mg / day. Platelet (PLT) transfusion was allowed when the platelet level was less than 20×10 9/L or with bleeding events. If platelet count increased to 100 ×10 9/L or 50 ×10 9/L more than baseline, which was defined as complete response (CR), treatment of avatrombopag was stopped. Results: The median age of 24 patients with CIT was 38 (range 17‒69) years, with 14 patients diagnosed with acute myeloid leukemia (AML), 9 patients diagnosed with acute lymphoblastic leukemia (ALL), and 1 patient diagnosed with mixed phenotype acute leukemia (MPAL). Chemotherapy regiments for patients with AML included decitabine combined with venetoclax (n=5), decitabine combined with arabinoside (n=3), arsenic trioxide combined with retinoic acid (n=3), azacytidine combined with venetoclax (n=2), azacytidine combined with medium-dose arabinoside (n=1). Chemotherapy regiments for patients with ALL included CD19 specific CAR-T cells (n=3), decitabine (n=2), blinatumomab (n=2), IVP (idarubicin, vindesine, and prednisone) (n=1), azacytidine combined with venetoclax and chidamide (n=1). Chemotherapy regiment for the patient with MPAL was decitabine combined with venetoclax (n=1). At baseline, 10 patients experienced grade 3 thrombocytopenia after chemotherapy, while 14 patients experienced grade 4 thrombocytopenia after chemotherapy. The median lowest platelet count was 19×10 9/L (range 1-47×10 9/L). During the treatment period, 14 patients received platelet transfusion. The median time to reach the CR standard was 6 (range 3-26) days, and no patients stopped treatment due to side effect or drug intolerance. Compared with using avatrombopag before, the levels of platelet count were significantly increased ( P=0.000 1). The optimal platelet count of 22 patients reached the standard of CR after 7 days of drug withdrawal. Conclusion: Avatrombopag is effective on increasing platelet counts in patients with acute leukaemia after chemotherapy, with a good safety profile. It is a suitable therapeutic option for thrombocytopenia after chemotherapy.

Efficacy and Safety of Avatrombopag in the Treatment of Thrombocytopenia after Umbilical Cord Blood Transplantation

Background: Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and it has no standard therapy. Avatromboapg is a second generation thrombopoietin receptor agonist (TPO-RA) and showed efficacy in immune thrombocytopenia (ITP). However, few reports focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: We conducted a retrospective study to evaluate the efficacy of avatrombopag in 69 patients after UCBT as the first-line thrombopoietin receptor agonist (TPO-RA) treatment. Results: Sixty-one patients were given avatrombopag to promote platelet engraftment, the other 8 for secondary failure of platelet recovery (SFPR). For the majority of patients (44/69, 63.8%), the initial dose was 40 mg daily. Among the 61 patients given avatrombopag for platelet engraftment, 40 achieved an overall response (OR) (65.6%), and the cumulative incidence of OR was 76.2% (95% CI, 61.3-86.0), at a median time of 23 days (range, 3-131 days). Thirty-eight of 61 (62.3%) patients achieved complete remission (CR), and the cumulative incidence of CR was 76.2% (95% CI, 61.1-86.1). Patients suffering from SFPR had a better cumulative incidence of OR [100% (95% CI, NA), P = 0.005]. Giving avatrombopag before 37 days post-UCBT was beneficial for OR in multivariate analysis. Conclusion: In summary, our results indicate that avatrombopag could be used to promote platelet engraftment, especially in the early period (&amp;lt; 37 days after UCBT). Patients with SFPR may have a better response to avatrombopag therapy. Keywords: Avatrombopag; umbilical cord blood transplantation; thrombopoietin receptor agonist; secondary failure of platelet recovery Conflict-of-interest disclosure: The authors declare that they have no competing interests.

Avatrombopag for adult chronic primary immune thrombocytopenia: a randomized phase 3 trial in China

BackgroundImmune thrombocytopenia (ITP) is an autoimmune disorder with decreased platelet counts and increased bleeding risk. ObjectivesTo evaluate the efficacy and safety of avatrombopag, a second-generation oral thrombopoietin receptor agonist, for the treatment of Chinese patients with chronic primary ITP. MethodsThis multicenter, randomized, double-blind, placebo-controlled phase 3 study (CTR20210431) consisted of a 6-week double-blind core treatment phase followed by a 20-week, open-label extension phase. Chinese adults with chronic primary ITP for at least 12 months and a platelet count <30 × 109/L were randomized (2:1) to receive avatrombopag (initial dose of 20 mg/day) or matched placebo. The primary endpoint was the proportion of subjects with a platelet count ≥50 × 109/L at week 6 of the core treatment phase in absence of rescue therapy. ResultsIn total, 74 patients were randomized (avatrombopag: N = 48; placebo: N = 26) between March 5, 2021, and August 6, 2021; all of whom entered the extension phase (72 received avatrombopag up to 26 weeks). At week 6 of the core study, the platelet response (≥50 x 109/L) rate was significantly higher in the avatrombopag group (77.1%; 95% CI, 62.7, 88.0) vs placebo (7.7%; 95% CI, 1.0, 25.1); the treatment difference was 69.4% (95% CI, 56.2, 86.3; P < .0001). During the 6-week core study, treatment-emergent adverse events were reported in 41 (85.4%) and 20 (76.9%) patients in the avatrombopag and placebo groups, respectively. The most common avatrombopag-related treatment-emergent adverse events were upper respiratory tract infection (14/48 [29.2%]), increased platelet count (13/48 [27.1%]) and headache (7/48 [14.6%]). ConclusionAvatrombopag was efficacious and generally well tolerated in Chinese patients with chronic primary ITP, with comparable efficacy and safety to previous reports in Western patients.

Avatrombopag, a promising novel thrombopoietin receptor agonist for refractory/relapsed/intolerant non-severe aplastic anemia: a phase 2 single-arm clinical trial

Introduction The therapeutic options for thrombocytopenia in non-severe aplastic anaemia (NSAA) are limited. Avatrombopag (AVA) is prescribed for thrombocytopenic diseases but not for NSAA. Methods Herein, we conducted a phase 2, non-randomized, single-arm trial to explore the efficacy and safety of AVA in refractory/relapsed/intolerant NSAA. AVA dose was initiated at 20 mg/d and titrated to a maximum of 60 mg/d. The primary endpoint was the haematological response at 3 months. Results Twenty-five patients were analyzed. The overall response rate (ORR) at 3 months was 56% (14/25), with 12% (3/25) achieving a complete response (CR). At a median follow-up of 7 (3–10) months, the OR and CR rates were 52% and 20%, respectively. Responders had a shorter duration of diagnosis of AVA administration than non-responders (10 (6–80) vs 37 (6–480) months, p = 0.027) and belonged to the relapsed/intolerant NSAA type (71% vs 27%, p = 0.047); 44% (8/18) patients previously treated with eltrombopag before enrollment responded at 3 months, with an average prior eltrombopag dose of median 72.5 (50–100) mg/d and an average AVA dose for a response of median 43.5 (20–60) mg/d. 3-month ORR had no significant correlation with eltrombopag exposure (p = 0.09), prior eltrombopag length (R 2=0.11), or cumulative eltrombopag dose (R 2=0.30). Only one patient relapsed after stopping AVA for 1 month. No serious AVA-related side effects or clone evolution were detected. Conclusion AVA is effective and well-tolerated in NSAA patients who are refractory, relapsed, or intolerant to CsA/tacrolimus ± eltrombopag. Earlier treatment and relapsed/intolerant AA may show a better short-term response rate. More studies are needed to define the optimal dose and the long-term efficacy (NCT04728789).

Efficiency and Safety of Avatrombopag in the Management of Thrombocytopenia with TPO or Tpora Ineffective：a Prospective, Single Arm, Exploratory Clinical Study

Thrombocytopenia refers to the sum of a series of clinical diseases with a platelet count of less than 100×109/L in peripheral blood, including primary immune thrombocytopenia (ITP), tumor chemotherapy-related thrombocytopenia (CIT), infection, etc. The traditional treatments of thrombocytopenia are not always effective and often lead to serious side effects. Therefore, thrombopoietin (TPO) and TPO receptor agonist (TPORA) have been found to play a role as early recombinant thrombopoietin and gradually become a new alternative treatment. At present, there are few studies on the treatment of thrombocytopenia with Avatrombopag, as a second-generation TPORA, at home and abroad. We designed a prospective, single arm, exploratory clinical study to evaluate the efficacy and safety of Avatrombopag in the treatment of thrombocytopenia with TPO or TPORA ineffective. The patients with platelet counts less than 25×109/L who have failed to respond to TPO or other TPORA (including Eltrombopag，Herombopag) treatment in the Fourth Affiliated Hospital of Medical College of Zhejiang University were recruited. All the eligible patients were administered oral Avatrombopag at an initial dose of 20mg/d or 40 mg/d, monitored complete blood count at least once a week, and adjusted the drug dose according to the platelet level. The efficacy and safety of the drug were analyzed by monitoring the changes of platelet level and bleeding grade within 4 weeks after treatment, and the adverse reactions of Avatrombopag. This study was registered at chictr.org.cn (ChiCTR2200061853). 22 patients were enrolled in the clinical trial, aged from 18 to 83 years, with a median age of 74 years, including 16 patients with immune thrombocytopenia (ITP), 5 patients with chemotherapy-induced thrombocytopenia (CIT) and one patient with thrombocytopenia caused by MDS. Baseline characteristics of patients enrolled in the study are shown in Table 1. During 4-w Avatrombopag treatment period, the median platelet count in ITP group was higher than that in CIT group (Table 2 and Figure 1). 20 patients (90.9%) had bleeding symptoms at baseline, which decreased to 36.4% (8/22) in the end of follow-up (Figure 2). After 4 weeks of treatment, 17 patients showed response to the drug (platelet count between 30 and 100×109/L, at least doubling of the baseline count, and absence of bleeding), with a median response time of 14 (5-27) days. Among them, 13 patients were ITP, 3 patients were CIT, and 1 patient was MDS-induced-thrombocytopenia. The difference was not statistically significant (p=0.654). 9 patients achieved complete response (platelet count higher than 100×109/L and absence of bleeding), all of them were ITP. Compared with CIT patients, the difference was statistically significant (p=0.045) (Table 3 and Figure 3). 20 of 22 patients (90.9%) no longer required platelet transfusion at the study end point. During the administration period, one patient was found to have mild liver dysfunction that is difficult to explain by other diseases, and the other patients were not found to have drug-related adverse effects. In conclusion, Avatrombopag is an effective and safe drug for the treatment of patients with relapse and refractory thrombocytopenia. Compared with CIT patients, Avatrombopag have faster response to platelets and higher remission rate for ITP patients. he research was supported by the Key R&D Program of Zhejiang, No. 2022C03137; Public Technology Application Research Program of Zhejiang, China, No. LGF21H080003; the Key Project of Jinhua Science and Technology Plan, China, No. 2020-3-011; the 2019-2022 Key Medical Discipline (Hematology) Fund of Jinhua, China. Correspondence to : Dr Jian Huang, Department of Hematology, The First Affiliated Hospital of Zhejiang University School of Medicine. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Thrombopoietin Levels Predict the Response to Avatrombopag Treatment in Patients with Persistent Thrombocytopenia after Haploidentical Hematopoietic Stem Cell Transplantation

Introduction: Persistent thrombocytopenia (PT) is a common and severe complication after haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HSCT), and there are currently no effective treatment strategies. Avatrombopag has shown promising results in the treatment of several thrombocytopenia disorders. However, no studies have examined the efficacy and safety of avatrombopag in the treatment of PT after haplo-HSCT, and predicting clinical response to avatrombopag before initiation is not possible. Thrombopoietin (TPO) is the chief cytokine that regulates megakaryocyte production and maturation, and endogenous TPO may be a biomarker of avatrombopag response. Methods: This study evaluated outcomes in patients who received the treatment of avatrombopag for persistent severe thrombocytopenia after haplo-HSCT between October 2019 and March 2022. On starting avatrombopag treatment, all included patients were with platelet counts ≤20×109/L and/or with platelet transfusion-dependence. Efficacy was assessed based on the platelet counts. Response was defined as platelet recovery to independence from platelet transfusion during or within 7 days after avatrombopag treatment, and complete response (CR) was defined as platelet recovery to ≥ 50×109/L for 7 consecutive days without platelet transfusion support. Endogenous TPO levels were measured by ELISA. Results: We report a cohort of 69 patients with PT after haplo-HSCT who were treated with avatrombopag. The 69 patients included 43 (62.3%) males and 26 (37.7%) females. The median age was 37 (11-60) years. Before starting avatrombopag therapy, the median platelet count was 15×109/L (range, 2-20×109/L). Forty patients (58.0%) had delayed platelet engraftment, and 29 patients (42.0%) had secondary failure of platelet recovery. Sixteen (23.2%) of the 69 patients had a history of using other TPO-RA (rhTPO or eltrombopag) for at least one round. Avatrombopag was initiated on a median of 59 (range 16-824) days after haplo-HSCT. Both the median starting and maximum doses were 40 mg daily. The rate of platelet recovery to transfusion independence was 72.5%, and the rate of platelet recovery to ≥ 50 ×109/L without transfusion support was 56.5%. Forty-seven (94.0%) of the 50 responders were able to taper off avatrombopag. The median duration of treatment was 40 (range 15-195) days. In addition, we present a novel clinical investigation of the use of TPO levels to predict the response to avatrombopag in patients with PT after haplo-HSCT. Logistic regression models demonstrated a significant predictive relation between TPO levels and probability of response. The TPO levels were inversely correlated with response (r = −0.998, P =0.011).(Figure) ROC analysis identified TPO levels ≤1714 pg/mL as the optimal threshold for discriminating responders and nonresponders. Based on univariate analysis, the presence of megakaryocytes in bone marrow before initiation (P=0.016), lower endogenous TPO levels (P =0.024) and no prior history of TPO-RA treatment (P =0.021) were independent factors that influenced the efficacy of avatrombopag. In the multivariate analysis, lower endogenous TPO levels (P =0.021) and no prior history of TPO-RA treatment (P=0.018) were independent factors that influenced the efficacy of avatrombopag. Avatrombopag was well tolerated in all patients, and patients responding to avatrombopag achieved improved overall survival (77.3% vs. 96.6%, P=0.008). Conclusions: Avatrombopag is a safe and effective therapy for severe PT after haplo-HSCT, and endogenous TPO levels prior to treatment could predict the response to avatrombopag. Key words: Avatrombopag, Persistent thrombocytopenia, Allogeneic hematopoietic stem cell transplantation, Haploidentical Figure legends：Multiple logistic regression models for the probability of response to avatrombopag based on endogenous TPO levels. The shaded area represents the 95% CI. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Efficacy and Safety of Avatrombopag in Combination with Immunosuppressive Therapy in Treatment-Naïve and Relapsed/Refractory Severe Aplastic Anaemia - the Diaamond-Ava-First and Diaamond-Ava-Next Bayesian Optimal Phase II Trials

Background: Improving treatment for patients with severe aplastic anemia (sAA) is a priority. Immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and ciclosporin is standard of care for patients with sAA not eligible or suitable for allogeneic stem cell transplant. While 50-75% of patients respond to IST, few achieve complete responses and a significant proportion are refractory or relapse. The addition of eltrombopag, a thrombopoietin-receptor agonist (TPO-A), to IST has been shown to improve hematological responses in sAA. Avatrombopag is a second-generation TPO-A, and like eltrombopag, lacks competitive binding with endogenous TPO, suggesting it may also be effective in AA. Avatrombopag has potential advantages over eltrombopag, including dosing, toxicity profile and pharmacokinetics. It has also been shown to have greater in vitro and in vivo pharmacological potency than eltrombopag. However, to date avatrombopag has not been studied in sAA. Methods: The DIAAMOND Ava-FIRST and DIAAMOND Ava-NEXT trials are investigator-initiated, non-randomised, single-arm registry-based Bayesian Optimal Phase II (BOP2) trials. The FIRST trial is evaluating avatrombopag in addition to IST in patients with untreated sAA. Patients receive IST (equine ATG and ciclosporin) plus avatrombopag from day 1 until day 180 at 60 mg oral daily and dose adjusted according to platelet count. Two primary endpoints, complete response (CR) rate and acquired clonal evolution (ACE) at 6 months are monitored at each interim analysis where a go/no-go decision is made by evaluating the posterior probability of the events of interest. The maximum sample size is 50 evaluable patients. The stopping boundaries were calculated with a target false positive rate of 10% under the global null as recommended in phase II studies. The performance of the trial and operating characteristics were assessed with 10,000 simulations. Other trial endpoints which are collected until 24 months following enrolment include rate and time to first hematological response, survival, cytogenetic evolution, progression to hematological malignancy, safety and quality of life. Exploratory assessments of interest include changes in iron studies and marrow iron stores, longitudinal cell free DNA somatic mutation analysis and T-cell receptor repertoire studies. In the NEXT trial, patients with relapsed or refractory sAA, six or more months following at least one course of horse or rabbit ATG are eligible. All patients receive avatrombopag at 60 mg oral daily from day 1 until day 180, further additional IST is at the discretion of the treating clinician. Two primary endpoints, hematological response (HR) rate and ACE are monitored at each interim analysis following which a go/no-go decision is made as described in the FIRST trial. The trials are embedded within the Australian Aplastic Anaemia and Other Bone Marrow Failure Syndromes Registry, which will allow long-term follow-up of participants after completion of the trial (at 24 months). Progress: The FIRST trial has enrolled 40 patients and the NEXT trial 16 patients. The dosing of avatrombopag was changed after the initial eleven patients were enrolled, when the starting dose was 20 mg daily and increased to a maximum of 60 mg daily over 8 weeks based on hematological response. This change was made based on observed tolerability of the maximum (60 mg) dose and timing of response rates. Interim analyses have been performed for both trials and stopping boundaries for efficacy or safety have not been met.

Effectiveness and Safety of Avatrombopag in Liver Cancer Patients with Severe Thrombocytopenia: Real-World Data and Challenges.

Avatrombopag has been approved in patients who have severe thrombocytopenia (<50 × 109/L) and chronic liver disease (CLD) while receiving invasive procedures. The real-world application and effectiveness of avatrombopag in the subgroup patients with liver cancer remain unknown. Liver cancer patients (including primary liver cancer and colorectal cancer liver metastasis) who had severe thrombocytopenia and received avatrombopag were retrospectively enrolled. Avatrombopag dose, peak and absolute platelet count increase, combination treatment with other thrombopoietic agents, responder (peak count ≥50 × 109/L with absolute increase ≥20 × 109/L) rate, and anticancer treatment effect were analyzed. Thrombosis and bleeding events were assessed. In total, 93 patients were enrolled, with 72 and 21 in the CLD and non-CLD groups, respectively. Patients with CLD had hepatitis B or C, larger spleen volume, and a higher cirrhosis degree. Baseline platelet counts were similar between two groups (median, 37.0 × 109/L vs. 39.0 × 109/L; P=0.594), while patients without CLD had higher peak platelet (median, 134.0 × 109/L vs. 74.0 × 109/L; P=0.015) and absolute increase (median, 101.0 × 109/L vs. 41.0 × 109/L; P=0.020) after avatrombopag treatment. The responder rate was higher in patients without CLD (100% vs. 76.4%; P=0.010). Combined avatrombopag with other thrombopoietic agents significantly increased platelet count; repeated use of avatrombopag produced similar effects with that of initial treatment. Concerning anticancer treatment effect, patients who responded to avatrombopag had a higher disease control rate. No thrombosis or hemorrhagic events were observed, even in patients with portal vein tumor thrombosis. Avatrombopag was safe and effective and ensured successful implementation of anticancer treatment in liver cancer patients with severe thrombocytopenia, accompanied with or without CLD.

Phase 2 study of avatrombopag in Japanese patients with chronic liver disease and thrombocytopenia.

Avatrombopag, a thrombopoietin receptor agonist, can reduce the need for platelet transfusions or rescue interventions for bleeding in patients with chronic liver disease (CLD) and thrombocytopenia undergoing scheduled procedures. A model analysis indicated that the effect of avatrombopag on platelet production was reduced in East Asian versus non-East Asian patients; however, the difference was deemed not clinically significant. Furthermore, a subgroup analysis of pooled Phase 3 trials showed similar avatrombopag efficacy across racial subgroups. The aim of this Phase 2 study was to corroborate the efficacy and safety of avatrombopag in Japanese patients with thrombocytopenia due to CLD. Japanese patients with CLD and thrombocytopenia were randomized to receive placebo or avatrombopag 20, 40, or 60mg daily for 5days. The primary endpoint was responder rate in platelet counts at Visit 4 (10-13days after treatment initiation), defined as the proportion of patients with platelet count ≥50×109 /L and ≥20×109 /L increase from baseline. Thirty-nine patients were randomized and completed the study (placebo, n=11; avatrombopag 20mg, n=7; 40mg, n=11; 60mg, n=10). Avatrombopag treatment was associated with significant increases in responder rate at Visit 4 in the 40mg (63.6%; p=0.004) and 60mg (40%; p=0.024) groups versus placebo (9.1%). Avatrombopag was well tolerated and no new safety signals were detected. Efficacy and safety results from this study were consistent with previous studies in patients with CLD and thrombocytopenia undergoing elective procedures, supporting treatment with avatrombopag in the Japanese population. gov identifier: NCT02227693.