sovleplenib (HMPL-523) / Hutchmed - LARVOL DELTA

Feasibility assessment of indirect treatment comparison between off-label rituximab and novel treatments in patients with warm autoimmune hemolytic anemia (ASH 2025) - "Among the clinical trials included, five studied rituximab, in combination with prednisone, prednisolone, ibrutinib, or bortezomib. Three trials studied fostamatinib, while other studied treatments included pegcetacoplan, sovleplenib, parsaclisib, and rilzabrutinib...Future work should consider de novo sources of real-world evidence for rituximab that more closely align with registrational trial characteristics and endpoint definitions. However, aligning timing of endpoint measurements between registration trials and real-world data to match definitions remains challenging."

Clinical • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology

Efficacy and safety of spleen tyrosine kinase inhibitors in chronic immune thrombocytopenic purpura: A meta-analysis of randomized controlled trials (ASH 2025) - "SYK inhibitors significantly improve platelet response in chronic ITP without increased thrombotic risk. Fostamatinib and the investigational agent sovleplenib both demonstrated efficacy compared to placebo. These agents may represent promising options for patients with refractory ITP, particularly those at risk of thrombosis from TPO-RAs."

Retrospective data • Cardiovascular • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Thrombocytopenia • Thrombocytopenic Purpura • Thrombosis • SYK

Phase 3 ESLIM-01 study: Final analysis of efficacy and safety of long-term treatment with sovleplenib in adults with chronic primary immune thrombocytopenia (ASH 2025) - P3 | "Major bleeding events (ISTH criteria) occurred in 2.2% of all Sov group and 3.8% of P-Sov group.The study had no mortality events.ConclusionsLong-term treatment with sovleplenib demonstrated clinically meaningful and sustained plateletresponses in adult pts with ITP in China, while maintaining a tolerable safety profile. These findingssupport sovleplenib as a promising therapeutic option for adult pts with chronic primary ITP."

Clinical • P3 data • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura • SYK

Management of Autoimmune Hemolytic Anemia (ASH 2025) - "For relapsed/refractory patients rituximab has become the preferred second line-therapy, comparing favorably with the traditional splenectomy, which has been progressively abandoned or moved to further lines along with classic immunosuppressors. Several novel treatments are in development for wAIHA, encompassing drugs targeting B-cells (parsaclisib, ibrutinib, rilzabrutinib, zanubrutinib, obexelimab, ianalumab, povetacicept), plasma cells (bortezomib, daratumumab), spleen tyrosine kinase (fostamatinib, sovleplenib), and the neonatal Fc receptor (nipocalimab)."

IO biomarker • Anemia • Autoimmune Hemolytic Anemia • Bone Marrow Transplantation • Hematological Disorders • Immunology • Infectious Disease • HP • SYK

Management of autoimmune hemolytic anemia. (PubMed, Hematology Am Soc Hematol Educ Program) - "Rituximab is now the preferred second-line option for relapsed/refractory patients, comparing favorably with the traditional splenectomy. The latter is increasingly reserved for later lines together with classic immunosuppressants. Several novel treatments are in development for refractory wAIHA, encompassing drugs targeting B-cells (parsaclisib, ibrutinib, rilzabrutinib, zanubrutinib, obexelimab, ianalumab, povetacicept), plasma cells (bortezomib, daratumumab), spleen tyrosine kinase (fostamatinib, sovleplenib), and the neonatal Fc receptor (nipocalimab)."

Journal • Review • Anemia • Autoimmune Hemolytic Anemia • Bone Marrow Transplantation • Complement-mediated Rare Disorders • Hematological Disorders • Immunology • Infectious Disease • Oncology • Paroxysmal Nocturnal Hemoglobinuria • Transplantation • SYK

Characterizing the Clinical, Humanistic, and Economic Burden of Warm Autoimmune Hemolytic Anemia: A Systematic Literature Review and Evidence Gap Assessment (ASH 2024) - "While there are no FDA-approved treatments specifically for wAIHA, treatments evaluated within the set of clinical trials included fostamatinib, rituximab, ibrutinib + rituximab, sovleplenib, parsaclisib, and pulse cyclophosphamide. While wAIHA is a relatively poorly studied disease, available data suggests low Hb levels and associated risks across both clinical trials and real-world study publications, reflecting a high unmet need in this patient population. Patient-reported outcomes, including health-related quality of life measures, should be evaluated with clinical outcomes in future trials and observational studies to facilitate understanding of outcomes that are important to patients."

Clinical • HEOR • Review • Anemia • Autoimmune Hemolytic Anemia • Fatigue • Hematological Disorders • Immunology

HUTCHMED Highlights Clinical Data to be Presented at…the 2025 ASH Annual Meeting (GlobeNewswire) - "Final analysis of long-term results of sovleplenib’s ESLIM-01 China Phase III study in in adult patients with chronic primary immune thrombocytopenia will be presented at the 2025 ASH Annual Meeting."

P3 data • Immune Thrombocytopenic Purpura

Long-Term Sovleplenib Treatment of Adults with Primary Immune Thrombocytopenia in China (ASH 2024) - P3 | "Conclusions Long-term treatment with sovleplenib was effective in increasing and maintaining platelet count with well tolerated safety in adults with chronic primary ITP in China. No new safety signals were identified."

Clinical • Cardiovascular • Hematological Disorders • Hypertension • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura • SYK

Sovleplenib for ITP and wAIHA (GlobeNewswire) - "Preparations for the resubmission of the new drug application for second-line immune thrombocytopenia (ITP) are progressing as outlined in the 2025 interim report, with resubmission planned for the second quarter of 2026. The ESLIM-02 study in second-line warm autoimmune hemolytic anemia (wAIHA) has completed enrollment, with topline results expected in early 2026."

China filing • Enrollment closed • P2/3 data • Autoimmune Hemolytic Anemia • Immune Thrombocytopenic Purpura

2018-523-00US1: An Open-label, Dose Escalation Trial to Evaluate the Safety and Pharmacokinetics of HMPL-523 in Patients With Lymphoma (clinicaltrials.gov) - P1 | N=87 | Terminated | Sponsor: Hutchmed | N=140 ➔ 87 | Trial completion date: Jan 2026 ➔ Mar 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2024 ➔ Mar 2025; Study terminated by sponsor

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

The Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of HMPL-523 in Adult Subjects With Immune Thrombocytopenia (ITP) (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Hutchmed | N=48 ➔ 0 | Recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Thrombocytopenia • Thrombocytopenic Purpura

Beneath the surface in autoimmune hemolytic anemia: pathogenetic networks, therapeutic advancements and open questions. (PubMed, Front Immunol) - "Glucocorticoids remain the standard first-line therapy for warm AIHA; in contrast, CAD/CAS is increasingly managed with agents targeting B-cell function or complement activation, including rituximab and sutimlimab...Emerging therapeutics targeting the classical complement pathway include novel anti-C1s monoclonal antibodies such as riliprubart, which exhibits an extended half-life due to enhanced affinity for the neonatal Fc receptor. Parallel strategies aim to disrupt B-cell receptor (BCR) signaling cascades, employing Bruton tyrosine kinase (BTK) inhibitors such as ibrutinib, spleen tyrosine kinase (SYK) inhibitors such as fostamatinib and sovleplenib, and phosphoinositide 3-kinase (PI3K) inhibitors such as parsaclisib. Collectively, these advances are reshaping the therapeutic landscape of AIHA toward a precision medicine model guided by mechanistic insights into disease biology. In this review, we delineate the evolving immunopathogenesis of AIHAs and examine..."

Journal • Review • Anemia • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Immunology • SYK

Future directions in the management of warm autoimmune hemolytic anemia (PubMed, Rinsho Ketsueki) - "Rituximab and splenectomy are effective second-line treatments; however, there is no consensus on the optimal therapeutic approach for patients with wAIHA that is refractory to second-line therapy...Nipocalimab, a fully human IgG1 monoclonal antibody targeting FcRn, is expected to be effective in wAIHA by reducing the half-life of pathogenic IgG autoantibodies. Fostamatinib, an SyK inhibitor approved for the treatment of chronic immune thrombocytopenia in adults, demonstrated a significantly higher rate of sustained hemoglobin responses compared to placebo in the global, randomized, double-blind, placebo-controlled phase 3 FORWARD trial. The efficacy of Sovleplenib, another SyK inhibitor, was also demonstrated in a randomized, double-blind, placebo-controlled phase 2 trial."

Clinical • Journal • Review • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Thrombocytopenia • Thrombocytopenic Purpura • SYK

STUDY DESIGN OF PHASE 3 PART IN A PHASE 2/3 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO ASSESS THE EFFICACY AND SAFETY OF SOVLEPLENIB IN WARM AUTOIMMUNE HAEMOLYTIC ANAEMIA (ESLIM-02) (EHA 2025) - P2/3 | "Treatment options for wAIHA are scarce after front-line treatments with corticosteroids and rituximab.Spleen tyrosine kinase (Syk) plays crucial roles in the FcγR signaling pathway of macrophages and B-cell activation. Phase 2 part of the phase 2/3 study provided proof of concept for the phase 3 part of the study of sovleplenib in pts with wAIHA. The phase 3 study is currently ongoing in China."

Clinical • P2/3 data • P3 data • Anemia • Autoimmune Hemolytic Anemia • Fatigue • Hematological Disorders • Immunology • SYK

Efficacy and Safety of Syk and BTK Inhibitors in Immune Thrombocytopenia: A Comprehensive Review of Emerging Evidence. (PubMed, Mediators Inflamm) - "Fostamatinib, an FDA-approved Syk inhibitor, has shown efficacy in enhancing platelet counts and reducing bleeding events in refractory ITP patients. Among the newer Syk inhibitors, sovleplenib demonstrated rapid and sustained platelet increases in clinical trials, with an 80% response rate at the 300 mg dosage and a favorable safety profile. Additionally, BTK inhibitors, including rilzabrutinib and orelabrutinib, have shown potential in clinical trials, offering increased platelet stability and favorable safety profiles in ITP cases. Syk and BTK inhibitors hold potential as targeted therapies for refractory ITP, with evidence supporting their ability to improve clinical outcomes and enhance patient quality of life. Continued research is warranted to optimize these therapies and confirm their long-term efficacy and safety in diverse patient populations."

Journal • Review • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Thrombocytopenia • Thrombocytopenic Purpura • SYK

HUTCHMED Reports 2024 Full Year Results and Provides Business Updates (GlobeNewswire) - "Potential upcoming clinical milestones for sovleplenib: Complete ESLIM-01 NMPA NDA review around end 2025 (NCT05029635). Complete enrollment of ESLIM-02 Phase III in the second half of 2025 (NCT05535933)."

China approval • Enrollment status • Anemia • Thrombocytopenia

ESLIM-01: Phase III Study on HMPL-523 for Treatment of ITP (clinicaltrials.gov) - P3 | N=272 | Active, not recruiting | Sponsor: Hutchison Medipharma Limited | Trial primary completion date: Oct 2024 ➔ Mar 2025

Trial primary completion date • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura

Sovleplenib in patients with primary or secondary warm autoimmune haemolytic anaemia: results from phase 2 of a randomised, double-blind, placebo-controlled, phase 2/3 study. (PubMed, Lancet Haematol) - P2/3 | "Sovleplenib treatment achieved an encouraging overall haemoglobin response in Chinese patients with warm autoimmune haemolytic anaemia and was well tolerated. The phase 3 part of the study (ESLIM-02) is currently ongoing to further substantiate the efficacy and safety of sovleplenib in this setting."

Journal • P2/3 data • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology • Oncology

Novel treatments for immune thrombocytopenia: targeting platelet autoantibodies. (PubMed, Expert Rev Hematol) - "Treatments outlined in this review include a) FcRn antagonists (efgartigimod), b) complement inhibitors (sutimlimab), c) B-cell directed therapies such as BTK inhibitors (rilzabrutinib), anti-BAFF agents (belimumab, ianalumab), and Syk inhibitors (fostamatinib, sovleplenib), d) plasma-cell directed therapies (daratumumab, bortezomib), and e) cellular therapeutic products. Platelet antibodies are often elusive in ITP; yet novel treatments targeting this pathway reinforce their role in the pathogenesis of this autoimmune platelet disorder."

Journal • Review • Hematological Disorders • Immunology • Thrombocytopenia • Thrombocytopenic Purpura • SYK

Human Mass Balance of [14C]HMPL-523 in Healthy Adult Male Chinese Subjects (clinicaltrials.gov) - P1 | N=6 | Completed | Sponsor: Hutchmed | Active, not recruiting ➔ Completed | N=10 ➔ 6

Enrollment change • Trial completion • Hematological Disorders • Thrombocytopenia

ESLIM-01: Phase III Study on HMPL-523 for Treatment of ITP (clinicaltrials.gov) - P3 | N=272 | Active, not recruiting | Sponsor: Hutchison Medipharma Limited | N=188 ➔ 272 | Trial completion date: Dec 2023 ➔ Jun 2025 | Trial primary completion date: Dec 2023 ➔ Oct 2024

Enrollment change • Trial completion date • Trial primary completion date • Hematological Disorders • Thrombocytopenia • Thrombocytopenic Purpura

A Study of Hutchison MediPharma Limited(HMPL)-523 in Patients With Relapsed or Refractory Mature B-cell Neoplasms (clinicaltrials.gov) - P1 | N=134 | Completed | Sponsor: Hutchison Medipharma Limited | Unknown status ➔ Completed | N=217 ➔ 134

Enrollment change • Trial completion • Oncology

wAIHA: HMPL-523 (Sovleplenib) in the Treatment of Warm Antibody Autoimmune Hemolytic Anemia (clinicaltrials.gov) - P2/3 | N=110 | Recruiting | Sponsor: Hutchison Medipharma Limited | Active, not recruiting ➔ Recruiting

Enrollment open • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology

The Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of HMPL-523 in Immune Thrombocytopenia Patients (clinicaltrials.gov) - P1 | N=45 | Completed | Sponsor: Hutchison Medipharma Limited | Unknown status ➔ Completed

Trial completion • Hematological Disorders • Thrombocytopenia • Thrombocytopenic Purpura

SOVLEPLENIB IN PRIMARY IMMUNE THROMBOCYTOPENIA (ITP) PTS WITH PRIOR TPO/TPO-RA TREATMENT: SUBGROUP ANALYSIS OF A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 3 STUDY (ESLIM-01) (EHA 2024) - P3 | "4%), eltrombopag (73, 54. 5%), hetrombopag (28,20. 9%), avatrombopag (28, 20. 9%) and romiplostim (10, 7... Sovleplenib significantly and consistently improved platelet counts in primary ITP pts with prior TPO/TPO-RAtreatments, regardless of TPO/TPO-RA treatment types and number of prior regimens. Sovleplenib could be aneffective treatment option for patients with primary ITP."

Clinical • P3 data • Hematological Disorders • Thrombocytopenia • Thrombocytopenic Purpura • SYK