Editor’s Note: From December 7–10, 2024, the 66th Annual Meeting of the American Society of Hematology (ASH) convened in San Diego, USA, drawing global experts and scholars to discuss the latest advancements in hematology. In recent years, increasing insights into the pathogenesis of immune thrombocytopenia (ITP) have paved the way for innovative treatment strategies, among which SYK inhibitors have garnered significant attention due to their unique mechanisms of action. At this year’s ASH conference, Dr. Hu Zhou from Henan Cancer Hospital shared his team’s latest findings (711) on this front, offering fresh perspectives for future therapeutic strategies. Hematology Frontier invited Dr. Zhou for an in-depth discussion on his study and its clinical significance.

Study Title：Preliminary Efficacy and Safety Results of TQB3473, a Novel Syk Inhibitor, in Adult Patients with Immune Thrombocytopenia (ITP)

Hematology Frontier: What inspired this study, and what unique advantages does TQB3473 have over other SYK inhibitors in terms of molecular mechanism or drug characteristics?

Dr. Hu Zhou: ITP is a chronic condition that, while benign, presents significant challenges due to the limitations of current treatments. First-line options such as corticosteroids and IVIG may show early efficacy, but their long-term response rates are only around 30%. This leaves 60–70% of patients without lasting benefits. Similarly, second-line treatments, including TPO receptor agonists, rituximab, and splenectomy, effectively address only 60–70% of cases, leaving 30–40% of patients with inadequate outcomes. This underscores the need for innovative drugs targeting novel mechanisms to address the unmet needs of relapsed/refractory ITP patients.

TQB3473, as a novel SYK inhibitor, works by inhibiting splenic macrophage-mediated platelet destruction. Platelets coated with specific antibodies are typically cleared by splenic macrophages. By effectively blocking SYK kinase activity, TQB3473 disrupts this destructive pathway, thereby preserving platelet levels.

Hematology Frontier: The study reported varying response rates and durability of remission across dose levels and subgroups. What do you see as the most promising aspects of these results, and what insights do they offer for future clinical applications and research directions?

Dr. Hu Zhou: This study enrolled 36 patients across three dose levels—400 mg, 600 mg, and 800 mg QD—using a 3+3 design. While the 400 mg group showed no response, all three patients in the 600 mg group demonstrated significant responses. Consequently, we expanded the 600 mg cohort to include 24 additional patients while also adding a few cases to the 800 mg group. However, the primary focus remained on the 600 mg group.

Over the 24-week study, the primary efficacy endpoint was the proportion of patients achieving a platelet count ≥50×10⁹/L at least once within 12 weeks without rescue treatment. Remarkably, 63% of patients in the 600 mg group achieved this endpoint.

Comparatively, fostamatinib achieved a 43% overall response rate in its Phase III trial, while TQB3473 demonstrated over 60% response rates in this Phase II trial (not a head-to-head comparison). Encouraged by these results, the Chinese National Medical Products Administration (NMPA) has approved Phase III trials for TQB3473. Other SYK inhibitors, such as Sykalib, have also shown promising efficacy in Phase III trials, signaling a bright future for this class of drugs in ITP management.

Safety outcomes for TQB3473 were also favorable, with only mild, manageable increases in liver enzymes and no thrombotic events or deaths, underscoring its tolerability.

Hematology Frontier: Based on the preliminary results, what are your expectations for the future development of SYK inhibitors in ITP treatment? What impact do you anticipate they will have on the field?

Dr. Hu Zhou: The incidence of ITP is approximately 5 per 100,000 people annually, translating to nearly 70,000 new cases in China each year. Unfortunately, many patients struggle to achieve optimal treatment outcomes due to the complex interplay of B-cell and T-cell activity and platelet production and destruction in the disease mechanism.

SYK inhibitors like TQB3473 offer a distinct mechanism of action by targeting splenic macrophage function. This sets them apart from conventional therapies and suggests their potential as standalone or combination treatments with other agents.

Looking ahead, the development of novel therapies with unique mechanisms remains a priority to address the unmet needs of relapsed/refractory ITP patients. Such innovations will expand treatment options, improve quality of life, and drive the ITP treatment landscape toward greater efficacy and patient satisfaction.