A multicenter phase II study on the efficacy and safety of hetrombopag in patients with severe aplastic anemia refractory to immunosuppressive therapy

Guangxin Peng, Guangsheng He, Hong Chang, Sujun Gao, Xinjian Liu, Tong Chen, Pei Li, Bing Han, Miao Miao, Zheng Ge, Xiaoyan Ge, Fei Li, Yingmei Li, Shunqing Wang, Yi Wang, Yaqi Shen, Tao Zhang, Jianjun Zou, Fengkui Zhang, Guangxin Peng, Guangsheng He, Hong Chang, Sujun Gao, Xinjian Liu, Tong Chen, Pei Li, Bing Han, Miao Miao, Zheng Ge, Xiaoyan Ge, Fei Li, Yingmei Li, Shunqing Wang, Yi Wang, Yaqi Shen, Tao Zhang, Jianjun Zou, Fengkui Zhang

Abstract

Background: In this single-arm phase II study (NCT03557099), we evaluated the efficacy and safety of hetrombopag, a small molecule thrombopoietin (TPO) receptor agonist, in patients with severe aplastic anemia (SAA) who were refractory to standard first-line immunosuppressive therapy (IST).

Methods: SAA patients who were refractory to standard first-line IST were given hetrombopag orally at an initial dose of 7.5 mg once daily to a maximum of 15 mg once daily, for a total of 52 weeks. The primary endpoint was proportion of patients achieving hematologic responses in ⩾1 lineage at week 18.

Results: A total of 55 eligible patients were enrolled and received hetrombopag treatment. This study met its primary endpoint, with 23 [41.8%, 95% confidence interval (CI) = 28.7-55.9] patients achieving hematologic response in ⩾1 lineage at week 18 after initiation of hetrombopag treatment. Twenty-four (43.6%, 95% CI = 30.3-57.7) and 27 (49.1%, 95% CI = 35.4-62.9) of the 55 patients responded in ⩾1 lineage at weeks 24 and 52, respectively. Median time to initial hematologic response was 7.9 weeks (range = 2.0-32.1). The responses were durable, with a 12-month relapse-free survival rate of 82.2% (95% CI = 62.2-92.2). Adverse events occurred in 54 (98.2%) patients, and 28 (50.9%) patients had treatment-related adverse events. Seventeen (30.9%) patients had adverse events of grade ⩾3. Serious adverse events occurred in 15 (27.3%) patients and three deaths (5.5%) were reported.

Conclusion: Hetrombopag showed encouraging efficacy with durable hematologic responses in patients with SAA who were refractory to IST. Hetrombopag was well tolerant and safe for long-term use.

Clinicaltrialsgov identifier: NCT03557099.

Keywords: clinical trial; hematologic response; hetrombopag; severe aplastic anemia; thrombopoietin receptor.

Conflict of interest statement

Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Yaqi Shen, Tao Zhang, and Jianjun Zou are employees of Jiangsu Hengrui Pharmaceuticals Co., Ltd. Other co-authors declare no competing interests.

© The Author(s), 2022.

Figures

Figure 1.
Figure 1.
Study profile.
Figure 2.
Figure 2.
Lineage characteristics of hematologic responses to hetrombopag. The Venn diagrams show the number of patients with unilineage, bilineage, and trilineage hematologic responses at week (a) week 18, (b) week 24 and (c) 52
Figure 3.
Figure 3.
Hematologic improvements over time from baseline: Data are mean of (a) platelet counts, (b) hemoglobin concentration, (c) neutrophil counts, and (d) reticulocyte counts during treatment with hetrombopag from baseline to week 52.

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