sovleplenib (HMPL-523) / Hutchmed - LARVOL DELTA

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

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

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

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

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

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

SOVLEPLENIB FOR THE TREATMENT OF WARM ANTIBODY AUTOIMMUNE HEMOLYTIC ANEMIA (WAIHA): RESULTS FROM THE RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE 2 PART OF THE STUDY (EHA 2024) - P2/3 | "Sovleplenib demonstrated a favourable safety profile and an encouraging Hb benefit compared with placebo. The randomized phase 3 study (ESLIM-02) will further investigate the efficacy and safety of sovleplenib 300 mgQD for the treatment of wAIHA."

Clinical • P2 data • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology • Thrombocytopenia • Thrombocytopenic Purpura • CD63 • SYK

EFFICACY AND SAFETY OF THE SYK INHIBITOR SOVLEPLENIB (HMPL-523) IN ADULT PATIENTS WITH PRIMARY IMMUNE THROMBOCYTOPENIA IN CHINA (ESLIM-01): A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 3 STUDY (EHA 2024) - P3 | "Sovleplenib demonstrated a clinically meaningful early and sustained durable platelet response in primary ITPpatients, with a tolerable safety profile and improvement in patient quality of life. Sovleplenib could be apotential treatment option for ITP who have received ≥1 prior therapy."

Clinical • P3 data • Fatigue • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Thrombocytopenia • Thrombocytopenic Purpura • SYK

A PHASE 1B STUDY TO EVALUATE THE SAFETY AND PRELIMINARY EFFICACY OF SOVLEPLENIB, A SYK INHIBITOR, IN ADULT SUBJECTS WITH IMMUNE THROMBOCYTOPENIA (EHA 2024) - P1, P3 | "Sovleplenib, adifferentiated syk inhibitor, has shown increased selectivity compared to fostamatinib in pre-clinical studies. The Phase Ib 2022-523-GLOB1 study will evaluate the safety and efficacy of sovleplenib in Western pts whowere diagnosed with primary ITP, and will determine the RP3D of sovleplenib."

Clinical • P1 data • Hematological Disorders • Thrombocytopenia • Thrombocytopenic Purpura • SYK

SOVLEPLENIB IN PRIMARY IMMUNE THROMBOCYTOPENIA (ITP) PATIENTS BY PRIOR LINES OF THERAPY: SUBGROUP ANALYSIS OF A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 3 STUDY (ESLIM-01) (EHA 2024) - P3 | "In the post hoc analysis, sovleplenib showed consistent benefit in adult ITP, even ifsome patients had received multiple prior ITP therapies before sovleplenib initiation, without any impairingeffect in safety profile."

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

SAFETY AND EFFICACY OF SYK INHIBITOR SOVLEPLENIB IN HEAVILY PRE-TREATED HODGKIN LYMPHOMA PATIENTS (EHA 2024) - P1 | "Majority of the pts had received prior treatment with PD-1inhibitor (92%) or brentuximab vedotin (92%) or both (88%) and 44% had received autologous stem celltransplant. Sovleplenib was well tolerated at the RP2D of 700 mg QD in R/R HL pts. Encouraging proof of activity wasdemonstrated in heavily pre-treated patients, most of whom had disease failure with PD-1 inhibitor and/orbrentuximab vedotin. Additional studies are needed to evaluate the value of SYK-inhibitor as eithermonotherapy or combination in this challenging population with a high unmet need for therapeutic options."

Clinical • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Immunology • Leukopenia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation • SYK

Efficacy and safety of sovleplenib (HMPL-523) in adult patients with chronic primary immune thrombocytopenia in China (ESLIM-01): a randomised, double-blind, placebo-controlled, phase 3 study. (PubMed, Lancet Haematol) - P3 | "Sovleplenib showed a clinically meaningful sustained platelet response in patients with chronic primary immune thrombocytopenia, with a tolerable safety profile and improvement in quality of life. Sovleplenib could be a potential treatment option for patients with immune thrombocytopenia who received one or more previous therapy."

Journal • P3 data • Cardiovascular • Hematological Disorders • Hypertension • Oncology • Thrombocytopenia • Thrombocytopenic Purpura • SYK

Sovleplenib in immune thrombocytopenia. (PubMed, Lancet Haematol) - No abstract available

Journal • Hematological Disorders • Thrombocytopenia • Thrombocytopenic Purpura

HUTCHMED Highlights Publication of Phase III ESLIM-01 Results in The Lancet Haematology (GlobeNewswire) - P3 | N=188 | ESLIM-01 (NCT05029635) | Sponsor: Hutchison Medipharma Limited | "Additional details and subgroup results of the study were also presented on June 14 at the...EHA 2024 Hybrid Congress as an oral and two poster presentations....Further post-hoc subgroup analysis of the study demonstrated consistent clinical benefits across ITP patients regardless of prior lines of ITP therapies or prior TPO/TPO-RA exposure, including TPO/TPO-RA treatment types and number of prior regimens. Most patients were heavily pretreated with a median of four prior lines of ITP therapy. In patients who received four or more prior lines of therapy, the durable response rate was 47.7% with sovleplenib compared to 0% with placebo (p<0.0001). In addition, a majority of the patients had received prior TPO/TPO-RA. 74.6% of patients in the sovleplenib group had received prior treatment with TPO/TPO-RA, and analysis in this subgroup also demonstrated a significantly higher durable response..."

P3 data • Thrombocytopenia

Efficacy and safety of sovleplenib (HMPL-523) in adult patients with chronic primary immune thrombocytopenia in China (ESLIM-01): a randomised, double-blind, placebo-controlled, phase 3 study (Lancet Haematol) - P3 | N=188 | ESLIM-01 (NCT05029635) | Sponsor: Hutchison Medipharma Limited | "Between Sept 29, 2021, and Dec 31, 2022, 188 patients were randomly assigned to receive sovleplenib (n=126) or placebo (n=62). 124 (66%) were female, 64 (34%) were male, and all were of Asian ethnicity. Median previous lines of immune thrombocytopenia therapy were 4·0, and 134 (71%) of 188 patients had received previous thrombopoietin or thrombopoietin receptor agonist. The primary endpoint was met; durable response rate was 48% (61/126) with sovleplenib compared with zero with placebo (difference 48% [95% CI 40–57]; p<0·0001). The median time to response was 8 days with sovleplenib compared with 30 days with placebo."

P3 data • Thrombocytopenia

HUTCHMED Highlights Sovleplenib Phase III ESLIM-01 Study and Hematological Malignancy Programs Data to be Presented at the upcoming EHA2024 Congress (GlobeNewswire) - P2/3 | N=110 | ESLIM-02 (NCT05535933) | Sponsor: Hutchison Medipharma Limited | "Results from Phase II part of the ongoing ESLIM-02 Phase II/III study (NCT05535933) of sovleplenib for warm antibody autoimmune hemolytic anemia (wAIHA) will also be presented at the congress demonstrating encouraging hemoglobin (Hb) benefit compared with placebo, with overall response rate of 43.8% vs. 0% in the first 8 weeks, and overall response rate of 66.7% during the 24 weeks of sovleplenib treatment (including patients that crossed over from placebo). A favorable safety profile was also demonstrated."

P2 data • Autoimmune Hemolytic Anemia

HUTCHMED Highlights Sovleplenib Phase III ESLIM-01 Study and Hematological Malignancy Programs Data to be Presented at the upcoming EHA2024 Congress (GlobeNewswire) - P3 | N=188 | ESLIM-01 (NCT05029635) | Sponsor: Hutchison Medipharma Limited | "HUTCHMED (China) Limited...announces that topline and subgroup results from the ESLIM-01 Phase III study of sovleplenib....will be presented at the upcoming European Hematology Association ('EHA') Hybrid Congress....ESLIM-01 is a randomized, double-blinded, placebo-controlled Phase III trial in China....In 188 patients randomized to receive oral sovleplenib or placebo, sovleplenib demonstrated a clinically meaningful early and sustained durable platelet response in patients with primary ITP with durable response rate of 48.4% compared to zero with placebo (p<0.0001). The median time to response was 1.1 weeks with sovleplenib. It demonstrated a tolerable safety profile with grade 3 or above treatment-emergent adverse events (TEAEs) in 25.4% of patients with sovleplenib and 24.2% with placebo. Sovleplenib also significantly improved quality of life in physical functioning and energy/fatigue (p<0.05)."

P3 data • Thrombocytopenia • Thrombocytopenic Purpura