Tavalisse (fostamatinib) / Rigel, Inmagene, Kissei, JW Pharma, Grifols, Knight Therap - LARVOL DELTA

FOSTA-ARDS: Fostamatinib for Treating Acute Respiratory Distress Syndrome (ARDS) in Hospitalized Adults (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: Inova Health Care Services | Initiation date: May 2025 ➔ Jul 2025

Trial initiation date • Acute Respiratory Distress Syndrome • Pulmonary Disease • Respiratory Diseases

Integrated DNA Methylome and Transcriptome Analysis Reveals Novel Pathways and Cell Types in the Pathogenesis of Erdheim-Chester Disease (EULAR 2025) - "Besides, drug repurposing analyses proposed potential therapeutic agents for ECD, including fostamatinib and auranofin, both of which target IKBKB, a key component of the NF-kappaB signaling cascade. This study provides key insights into ECD pathogenesis through the first integrative epigenomic and transcriptomic analysis in this condition. Our results highlight disruptions in various neoplastic and inflammatory pathways, identifying B cells and NF-kappaB signaling as relevant factors to disease progression, and revealing IKBKB as a therapeutic target with existing drug options."

Epigenetic controller • IO biomarker • Oncology • Rare Diseases • IKBKB • LRRC1

Drug repurposing of fostamatinib against cancer via potential cytotoxicity and immune checkpoint regulation. (PubMed, Front Immunol) - "Moreover, fostamatinib downregulated the expression of immune checkpoints such as PD-L1 and CD47. Overall, this study provided a conceptual foundation for evaluating the advantages of drug repurposing in AML drug development."

IO biomarker • Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Immune Thrombocytopenic Purpura • Leukemia • Oncology • Thrombocytopenia • Thrombocytopenic Purpura • FLT3 • PD-L1 • SYK

Ruxolitinib Plus Fostamatinib for Steroid Refractory cGvHD (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Stefanie Sarantopoulos, MD, PhD. | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology

Molecular alterations identified in a phase 1 study of fostamatinib plus paclitaxel in platinum-resistant ovarian cancer. (ASCO 2025) - P1 | "The molecular differences between patients with PR and PD to the Fos-wPac combination highlight potential resistance mechanisms, including alterations in energy metabolism, ribosomal dysfunction, and cellular proliferation. These findings provide groundwork for future validation studies to assess these pathways and genes as therapeutic targets in PROC."

P1 data • Platinum resistant • Oncology • Ovarian Cancer • Solid Tumor • ALDOA • MYCT1 • SYK

TREM2 inhibits LPS-induced pyroptosis and inflammation by promoting mitophagy via SYK in BV2 cells. (PubMed, Neurotoxicol Teratol) - "Conversely, SYK inhibition by R406 led to microglial cell death and aggravated neuroinflammation, thereby reducing the neuroprotective effects of TREM2. Our findings indicate that TREM2 and SYK mitigate the inflammatory response in LPS-induced BV2 microglia and interfere with pyroptosis by enhancing mitophagy. These findings suggest that TREM2 and SYK may be valuable therapeutic targets for neuroinflammation."

Journal • Cognitive Disorders • Inflammation • NLRC5 • NLRP3 • SYK • TREM2

Antibody-mediated Rejection - Treatment Standard. (PubMed, Nephrol Dial Transplant) - "We conclude that steroids, rituximab, bortezomib, and interleukin-6 (IL-6) antagonists lack sufficiently robust evidence to support their use in AMR. Along these lines, in severe early AMR, complement inhibition may also be an option. Ongoing phase 2 trials evaluating prolonged courses of high dose IVIG, the neonatal Fc receptor blocker efgartigimod, the tyrosine kinase inhibitor fostamatinib, and the complement inhibitor BIVV020, along with phase 3 trials of the anti-IL-6 receptor antibody tocilizumab and the CD38 antibody felzartamab, offer hope for effective, approved therapies targeting different aspects of AMR pathobiology."

Journal • Antibody-mediated Rejection • Inflammation • Transplantation

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

PLATELET REACTIVITY IS VARIABLE IN PATIENTS WITH IMMUNE THROMBOCYTOPENIA AND CAN BE CORRECTED BY TREATMENT (EHA 2025) - "Current treatments, such as corticosteroids, intravenous immunoglobulin (IVIg), rituximab, and thrombopoietin receptor agonists (TPO-RAs) aim to increase platelet number. More recently, inhibitors of the Spleen Tyrosine Kinase (SYKi) and Bruton's Tyrosine Kinase (BTKi) have been either recently licensed (Fostamatinib) or are in clinical trial (Rilzabrutinib)... Some cohorts of ITP patients display either more or less reactive platelets compared to controls, irrespective of platelet count. This signifies a role for aberrant platelet function in the pathogenesis of ITP that may contribute to the heterogeneity of this disease. This study also found more fluctuation in platelet sensitivities in patients, with some moving between reactivity groups over an average of 3-4 months."

Clinical • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Thrombocytopenia • Thrombocytopenic Purpura • BTK • SYK

125I inhibits the progression of cervical cancer by upregulating the HSF1/PU.1/SYK signaling pathway and consequently enhancing the apoptotic response mediated by ROS/USP7/P53. (PubMed, Sci Rep) - "However, specific knockdown of HSF1 and the administration of the SYK inhibitor R406 can reverse the potentiating effect of 125I radiotherapy on the ROS/USP7/P53 pathway, consequently promoting the progression of cervical cancer; specific overexpression of PU.1 can abrogate the inhibitory impact of HSF1 knockdown on the ROS/USP7/P53 pathway, thereby suppressing the progression of cervical cancer. 125I inhibits the progression of cervical cancer by upregulating the HSF1/PU.1/SYK signaling pathway and consequently enhancing the apoptotic response mediated by ROS/USP7/P53."

Journal • Cervical Cancer • Infectious Disease • Oncology • Solid Tumor • CLEC7A • HSF1 • SYK • USP7

Drug repurposing of fostamatinib against cancer via potential cytotoxicity and immune checkpoint regulation (Frontiers) - "In this study, we pinpointed fostamatinib, an orally delivered small molecule SYK inhibitor for chronic immune thrombocytopenia (ITP), as a promising candidate for drug repurposing. It effectively inhibited FLT3-ITD+ AML cell proliferation and induced leukemic cell apoptosis. Network pharmacology analysis further deciphered the associated pharmacological mechanism related to the PI3K-AKT signaling pathway. Moreover, fostamatinib downregulated the expression of immune checkpoints such as PD-L1 and CD47. Overall, this study provided a conceptual foundation for evaluating the advantages of drug repurposing in AML drug development."

Preclinical • Acute Myelogenous Leukemia

EFFICACY AND SAFETY OF TPO-RA-BASED COMBINATION THERAPIES IN REFRACTORY IMMUNE THROMBOCYTOPENIA: A SINGLE-CENTRE COMPARISON OF 3 TPO-RA BASED TREATMENT STRATEGIES. (EHA 2025) - "All TPO-RA-based combination strategies demonstrated good efficacy in achieving platelet response in refractory ITP, indicating that combining immunomodulatory therapy with TPO-RAs appear to be a promising strategy in patients unresponsive to multiple monotherapies.Further studies with larger sample sizes and longer follow-up are needed to validate these findings, establish clear safety profiles and to identify optimal combination strategies for refractory ITP.Importantly, there remains a critical need to define the specific patient characteristics or biomarkers that can reliably predict the response to guide selection of combination therapy."

Clinical • Combination therapy • Cardiovascular • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Infectious Disease • Thrombocytopenia • Thrombocytopenic Purpura

The new era of primary immune thrombocytopenia management in adults: A narrative review of current and emerging treatments. (PubMed, Blood Rev) - "Specifically, we point out the indications for use of the various therapies available: corticosteroids, intravenous immunoglobulins (IVIG), thrombo- poietic agents (TPO-RAs), Syk inhibitors: Fostamatinib, antiCD20 monoclonal antibodies i.e. rituximab and the use of splenectomy in ITP. A review of the use of new drugs in ITP is also included in our manuscript: Neonatal Fc receptor (FcRn) antagonists; Bruton tyrosine kinase (BTK) inhibition; B-cell activating factor (BAFF) pathway inhibition; plasma cell depletion (an- tiCD38 monoclonal antibodies); new Syk inhibitors and complement inhibition. We believe that a reader with little knowledge of ITP can gain a clear understanding of the current treatment of ITP and its more or less immediate treatment prospects."

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

RETROSPECTIVE APPLICATION OF THE TH2 SCORE IN A MULTICENTER COHORT OF ITP PATIENTS: A RELIABLE PREDICTIVE TOOL OR A SCORE IN NEED OF REFINEMENT? (EHA 2025) - "SYKi (e.g., fostamatinib, FST) may help by mitigating inflammation... In one case, an increased TH2 predicted a CV event, but the score remained 1 post-event despite TPOra use. In other cases, low platelet counts likely limited score changes during therapy shifts. Except for one, no thrombotic events occurred despite prothrombotic score."

Retrospective data • Cardiovascular • Hematological Disorders • Immune Thrombocytopenic Purpura • Inflammation • Thrombocytopenia • Thrombocytopenic Purpura • Thrombosis

INDIRECT COMPARISON IN REAL LIFE BETWEEN 2 ORAL TREATMENTS IN ITP USING ARTIFICIAL INTELLIGENCE (EHA 2025) - "The potential of ChatGPT4o, in medicine, not only in hematology (https://codigorojo.tech/home/) is many and varied, as Van de Wyngaert (Haemophilia (2023) doi10.1111/hae.14858) reminds us, stating that "ChatGPT4o can be a valuable tool for patients and healthcare professionals, but it should not replace medical consultations or the experience of a multidisciplinary hemophilia team" Aims: Make an indirect comparison in terms of safety and efficacy between fostamatinib and avatrombopag base don results of two national studies in real life (Table 1). Obviously, this analyses have limitations; in general, statistical analysis performed is simplified and lacks adequate adjustments. Although the simplified analysis can provide a global view of the efficiency of both drugs, we must consider the mentioned limitations for an adequate interpretation of results. This analysis could be indicative for choosing between one or the other drug, considering the patient's..."

Clinical • Cardiovascular • Hematological Disorders • Hemophilia • Rare Diseases • Thrombosis

REAL WORLD EXPERIENCE OF DISCONTINUATION OF THROMBOPOIETIN RECEPTOR AGONIST (TPO-RA) IN PRIMARY IMMUNE THROMBOCYTOPENIA (ITP) (EHA 2025) - "The combinations were avatrombopag + fostamatinib; eltrombopag + mycophenolate; romiplostim + mycophenolate; romiplostim + mycophenolate + fostamatinib.29 patients were eligible to stop their TPO-RA. TPO-RA therapy can be safely discontinued in selected patients with primary ITP. The majority of patients stopping TPO-RA sustained adequate platelet counts to maintain haemostasis (≥20-30 x 109/L). A trial of TPO discontinuation could be considered in more patients in our centre, but shared-decision making is important in patients where there is clear reason for continued TPO-RA therapy."

Clinical • Real-world • Real-world evidence • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura

A PHASE I OPEN LABEL STUDY OF FOSTAMATINIB, A SYK INHIBITOR, IN PATIENTS WITH LOWER-RISK MYELODYSPLASTIC SYNDROME AND CHRONIC MYELOMONOCYTIC LEUKEMIA (EHA 2025) - P1 | "Background: Erythropoiesis-stimulating agents (ESA) and luspatercept are standard of care agents for lower-risk (LR) myelodysplastic syndromes (MDS). Fostamatinib is safe and tolerable in pts with lower-risk MDS and CMML. However, there was no observed clinical benefit in this heavily pretreated population. Further studies are needed to evaluate the role of SYK signaling in earlier stages of MDS and CMML or in clonal hematopoiesis."

Clinical • P1 data • Chronic Myelomonocytic Leukemia • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Immune Thrombocytopenic Purpura • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Thrombocytopenia • Thrombocytopenic Purpura • SYK

REAL-WORLD EFFICACY AND SAFETY OF FOSTAMATINIB FOR ADULT PATIENTS WITH IMMUNE THROMBOCYTOPENIA: ITALIAN MULTICENTER EXPERIENCE. FINAL RESULTS OF THE GIMEMA ITP1122 STUDY (EHA 2025) - "54% of pts had already received more than one TPO-RA and 23% had undergone splenectomy.41 pts (=43%) suffered from cardiovascular comorbidities or other cardiovascular/thrombotic risk factors before starting F, and 19 pts (20%) experienced a total of 23 previous thrombotic events.Twenty-nine (30%) pts received F concomitantly with other anti-ITP medications: corticosteroids (19%), IVIg (4%), romiplostim (3%), eltrombopag (1%), cyclosporin-A (2%), azathioprine (1%).Complete response (CR) and overall response (CR+R) to F, according to IWG criteria, were achieved in 30 (32%) and 69 (73%) pts, respectively. This Italian experience confirms the efficacy and safety of F in a heavily pretreated population of ITP pts. F was used in most cases as fourth or further line of therapy, after failure of TPO-RAs. Our findings indicate that a significant proportion of pts (45% of the overall population) benefit from F after 6 months, suggesting that this treatment may be considered as a..."

Clinical • Real-world • Real-world effectiveness • Real-world evidence • Cardiovascular • Hematological Disorders • Hypertension • Immune Thrombocytopenic Purpura • Neutropenia • Thrombocytopenia • Thrombocytopenic Purpura

EVALUATION OF ARTERIAL THROMBOSIS FREQUENCY AND RISK FACTORS IN PATIENTS WITH IMMUNE THROMBOCYTOPENIA (EHA 2025) - "9 patients were receiving Eltrombopag, 10 patients received corticosteroids and 2 patients received combined therapy. As a result, it should not be forgotten that the arterial thrombosis risk of ITP will increase both without treatment and during the treatment period. Patients should be questioned in detail about their comorbidities, atherosclerotic and thrombotic risk factors. ITP treatment options should be determined together with these risk factors."

Clinical • Atherosclerosis • Cardiovascular • Hematological Disorders • Immune Thrombocytopenic Purpura • Peripheral Arterial Disease • Thrombocytopenia • Thrombocytopenic Purpura • Thrombosis • Venous Thromboembolism

THE SYK INHIBITRO BAY 61-3606 DIHYDROCHLORIDE INDUCES APOPTOSIS OF ACUTE MYELOID LEUKEMIA CELLS BY MODULATING PI3K/AKT?NF/κB PATHWAY (EHA 2025) - "Current SYK inhibitors like Entospletinib, Mivavotinib, and Fostamatinib face limitations due to RAS/RAF/MEK/ERK pathway activation and off-target effects. BAY 61-3606 dihydrochloride significantly inhibits the proliferation of acute myeloid leukemia (AML) cells and induces apoptosis. Mechanistically, BAY 61-3606 dihydrochloride downregulates the expression of anti-apoptotic proteins MCL-1 and BCL-XL, thereby activating the apoptotic pathway in AML cells. Additionally, it inhibits the activation of several key signaling pathways, including P-SYK, PI3K/Akt, ERK, NF/κB, and JAK/STAT."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2L1 • MCL1 • SYK

How does real-life treatment with fostamatinib compare with the FIT1 and FIT2 studies? Results from the Italian GIMEMA study (EHA 2025) - "Sponsored by Grifols."

Clinical • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura

Fostamatinib in difficult-to-treat ITP: real-world evidence from the French CARMEN Registry (EHA 2025) - "Sponsored by Grifols."

Clinical • HEOR • Real-world • Real-world evidence • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura

Spanish experience with fostamatinib in ITP: efficacy, safety, and tapering insights from FOSTASUR and FOSTAMES studies (EHA 2025) - "Sponsored by Grifols."

Clinical • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura

TSS9009: Exploring real-world evidence of fostamatinib in immune thrombocytopenia (ITP): a comprehensive review of European data (EHA 2025) - "Sponsored by Grifols."

Clinical • HEOR • Real-world • Real-world evidence • Review • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura

Taurine and a-ketoglutarate induce innate immune memory in macrophages and facilitate the reactivation of latently infected HIV by ß-glucan and MDP. (IMMUNOLOGY 2025) - "Our studies further showed that taurine and AKG enhanced the training effect of previously identified stimuli such as Syk kinase inhibitors (SYKi IV or R406), β-glucan, and Muramyl dipeptide (MDP), the active component of the BCG vaccine...Our studies also showed that combined application of AKG or taurine with either MDP, β-glucan or SYKi IV, can reverse HIV latency in cell line models more efficiently than training with MDP, β-glucan or SYKi IV alone. We also show that combined application of taurine or AKG with MDP, β-glucan, or SYKi IV can efficiently reactivate HIV from PBMCs of people living with HIV.Keywords: Cells Monocytes/Macrophages; Infections Viral; Molecules Cytokines; Processes Memory"

Late-breaking abstract • Human Immunodeficiency Virus • Immunology • Infectious Disease • Oncology • IL6 • SYK