Safety, pharmacokinetics, and preliminary efficacy of hetrombopag in pediatric patients with aplastic anemia: A pilot study

Hetrombopag, a novel thrombopoietin receptor agonist (TPO-RA), has demonstrated efficacy in adult patients with aplastic anemia (AA), but its role in pediatric AA patients remains unknown. This study evaluated the safety, pharmacokinetic (PK) profile, and preliminary efficacy of hetrombopag in pediatric AA. This pilot study enrolled pediatric patients with AA who were ineligible for hematopoietic stem cell transplantation. Patients received hetrombopag in combination with immunosuppressive therapy. Safety, PK parameters, and hematologic response (HR) rates at 3 and 6 months were analyzed. A total of 21 pediatric patients were enrolled, including six patients aged 1–5 years, nine patients aged 6–11 years, and six patients aged 12–17 years. Among them, 18 patients had severe AA and 3 had non-severe AA. The most common treatment-related adverse events were transaminase increased (33.3%) and blood bilirubin increased (14.3%). PK analysis revealed age-dependent variability, with the 6–11-year cohort exhibiting the highest inter-individual variability and excessive plasma drug exposure. Among patients with SAA, as defined by the Chinese guideline criteria, the HR rate at 3 months was 55.6% (10/18; 95% CI: 21.5–69.2), and the complete response (CR) rate was 5.6% (1/18; 95% CI: 0.1–27.3). By 6 months, the HR rate had increased to 72.2% (13/18; 95% CI: 46.5–90.3), and the CR rate to 22.2% (4/18; 95% CI: 6.4–47.6). Hetrombopag, in combination with IST, demonstrated a favorable safety profile, preliminary efficacy, and age-dependent PK variability in pediatric AA. These findings support further investigation into individualized dosing strategies to optimize therapeutic outcomes in this population. The trial was registered prospectively at the Chinese Clinical Trial Registry (ChiCTR2300068312) on February 14, 2023.