Abstract
BackgroundHetrombopag, a novel thrombopoietin receptor agonist, has been found in phase I studies to increase platelet counts and reduce bleeding risks in adults with immune thrombocytopenia (ITP). This phase III study aimed to evaluate the efficacy and safety of hetrombopag in ITP patients.MethodsPatients who had not responded to or had relapsed after previous treatment were treated with an initial dosage of once-daily 2.5 or 5 mg hetrombopag (defined as the HETROM-2.5 or HETROM-5 group) or with matching placebo in a randomized, double-blind, 10-week treatment period. Patients who received placebo and completed 10 weeks of treatment switched to receive eltrombopag, and patients treated with hetrombopag in the double-blind period continued hetrombopag during the following open-label 14-week treatment. The primary endpoint was the proportion of responders (defined as those achieving a platelet count of ≥ 50 × 109/L) after 8 weeks of treatment.ResultsThe primary endpoint was achieved by significantly more patients in the HETROM-2.5 (58.9%; odds ratio [OR] 25.97, 95% confidence interval [CI] 9.83–68.63; p < 0.0001) and HETROM-5 (64.3%; OR 32.81, 95% CI 12.39–86.87; p < 0.0001) group than in the Placebo group (5.9%). Hetrombopag was also superior to placebo in achieving a platelet response and in reducing the bleeding risk and use of rescue therapy throughout 8 weeks of treatment. The durable platelet response to hetrombopag was maintained throughout 24 weeks. The most common adverse events were upper respiratory tract infection (42.2%), urinary tract infection (17.1%), immune thrombocytopenic purpura (17.1%) and hematuria (15%) with 24-week hetrombopag treatment.ConclusionsIn ITP patients, hetrombopag is efficacious and well tolerated with a manageable safety profile.Trial registration Clinical trials.gov NCT03222843, registered July 19, 2017, retrospectively registered.
Highlights
Hetrombopag, a novel thrombopoietin receptor agonist, has been found in phase I studies to increase platelet counts and reduce bleeding risks in adults with immune thrombocytopenia (ITP)
The durable platelet response to hetrombopag was maintained throughout 24 weeks
Patients were not eligible if they were diagnosed with secondary thrombocytopenia or graded MF ≥ 2 myelofibrosis based on the European Consensus Scale [12] or thrombophilia or showed evidence of HIV, hepatitis C or B infections; other blood coagulation disorders; venous or arterial thrombosis; malignant tumors; liver cirrhosis; portal hypertension or congestive heart failure (New York Heart Association [NYHA] class III/IV); arrhythmia; myocardial infarction; atrial fibrillation; or corrected QT interval prolongation within the previous 3 months
Summary
Hetrombopag, a novel thrombopoietin receptor agonist, has been found in phase I studies to increase platelet counts and reduce bleeding risks in adults with immune thrombocytopenia (ITP). This phase III study aimed to evaluate the efficacy and safety of hetrombopag in ITP patients. Primary immune thrombocytopenia (ITP) is characterized by increased platelet destruction and impaired platelet production, resulting in decreased platelet counts and increased bleeding risk [1]. The main principle of treatment strategies for ITP is to maintain a target platelet level of > 20–30 × 109/L, at least for symptomatic patients, in order to prevent severe bleeding episodes since the risk of major bleeding increases below this level [4, 5]. If patients do not respond to or have experienced recurrent relapse after first-line treatment, second-line therapy, such as thrombopoietin receptor agonists (TPO-RAs), rituximab or splenectomy, should be started [4, 6,7]
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