rilzabrutinib (SAR444671) / Sanofi - LARVOL DELTA

Rilzabrutinib, the first-in-class BTK inhibitor for ITP. (PubMed, Blood) - No abstract available

Journal

Evaluation of ACQ-5 components from the rilzabrutinib phase 2 asthma study (ERS 2025) - No abstract available

P2 data • Asthma • Immunology • Respiratory Diseases

Impact of rilzabrutinib on inflammatory responses in human mast cells and eosinophils (ERS 2025) - No abstract available

Inflammation

ISTH: new data highlight innovation from Sanofi’s pipeline in rare diseases (Sanofi Press Release) - "New data from 18 abstracts, including five oral presentations, will be presented at the 33rd congress of the International Society on Thrombosis and Haemostasis (ISTH) in Washington D.C., US from June 21 to 25, 2025, highlighting Sanofi as a leader in hemophilia committed to rare blood diseases. Data to be presented expand on the potential of rilzabrutinib to address the underlying immune dysregulation of immune thrombocytopenia (ITP) and strengthen Sanofi as a leader in hemophilia with ALTUVIIIO and the newly launched Qfitlia, aimed at providing more treatment options to help improve patients’ lives."

Clinical data • Hemophilia • Thrombocytopenia

LUNA 4: Study to Evaluate the Efficacy and Safety of Oral Rilzabrutinib in Adults With Immune Thrombocytopenia (ITP) Who Failed First-line Treatment (clinicaltrials.gov) - P3 | N=60 | Not yet recruiting | Sponsor: Sanofi

New P3 trial • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura

Press Release: Rilzabrutinib granted orphan drug designation in the US for sickle cell disease (GlobeNewswire) - "The US Food and Drug Administration (FDA) has granted orphan drug designation to rilzabrutinib, a novel, advanced, oral, reversible Bruton's tyrosine kinase (BTK) inhibitor that works via multi-immune modulation, to target a reduction in vaso-occlusive crises, which may occur via inflammation, in sickle cell disease."

Orphan drug • Sickle Cell Disease

Efficacy and safety of rilzabrutinib, an oral Bruton's Tyrosine Kinase Inhibitor, in patients with IgG4-related disease: Results from a 52-week, Phase 2, open-label, proof-of-concept study (EULAR 2025) - P2 | "Objectives: To evaluate the safety and efficacy of rilzabrutinib over 52-weeks in rituximab-refractory or rituximab-naïve patients with IgG4-RD. These results suggest rilzabrutinib might be a promising oral treatment for prevention of disease flares in patients with IgG4-RD."

Clinical • P2 data • Fibrosis • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Xerostomia • CD4

Rilzabrutinib attenuates inflammatory biomarkers in moderate-to-severe atopic dermatitis: A tape-strip proteomic analysis (SID 2025) - P2 | "BSA, EASI, and IGA improvements showed positive correlations with Th1 (TNF/CXCL10/CXCL11), Th2 (CCL7/ IL33), and T-cell activation (CD38/CCL8) related markers (r>0.75, p<0.05). We showed significant modulation of the proteomic skin profile of patients treated with rilzabrutinib TID, highlighting its therapeutic potential in managing AD."

Biomarker • IO biomarker • Late-breaking abstract • Omic analysis • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • CCL20 • CCL3 • CCL8 • CD38 • CXCL1 • CXCL10 • CXCL11 • CXCL9 • IL10 • IL12B • IL17A • IL18 • IL33 • IL6 • S100A12 • TGFB1

Bruton's tyrosine kinase (BTK) is indispensable in neutrophils to initiate and maintain skin inflammation in a model of pemphigoid diseases (SID 2025) - "In vitro, ibrutinib and other inhibitors of BTK, including rilzabrutinib and CGI-1746, inhibited neutrophil responses to immune complexes. The marked responsiveness of EBA to BTK inhibition results from a nonredundant role of BTK in relaying Fcγ receptor signaling in neutrophils to induce the release of LTB4. This highlights BTK as promising drug target to treat EBA and potentially other antibody-induced autoimmune disease."

Bullous Pemphigoid • Dermatitis • Dermatology • Dermatopathology • Immunology • Inflammation • BTK

RNA Sequencing Analysis of Nasal Brushings From Participants Administered Rilzabrutinib 1200 MG Demonstrated an Impact on Multiple Pathways Relevant for Asthma (ATS 2025) - P2 | "Rilzabrutinib 1200mg treatment is associated with BTK- and asthma-related pathway engagement in nasal respiratory epithelium, suggesting that rilzabrutinib 1200mg may prevent immune system activation, reduce tissue damage, and improve the respiratory tract in participants with moderate-to-severe asthma. Indeed, rilzabrutinib treatment resulted in reduced LOAC events and improvement in symptoms."

Asthma • Immunology • Respiratory Diseases • IL5

Reduction in the Use of Rescue Medication for Asthma Symptom Relief With Rilzabrutinib: Results From a Phase 2 Study (ATS 2025) - P2 | "Rilzabrutinib treatment in participants with poorly controlled moderate-to-severe asthma was associated with a reduction in LOAC events, which was mainly driven by a reduction in SABA use. Overall, the use of SABA was reduced with rilzabrutinib vs placebo in both cohorts over 12 weeks."

P2 data • Asthma • Immunology • Respiratory Diseases

LIBRA: The Efficacy and Safety of Rilzabrutinib in Patients Aged 10 to 65 Years With Sickle-cell Disease (clinicaltrials.gov) - P3 | N=192 | Recruiting | Sponsor: Sanofi

New P3 trial • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

PHASE 3 LUNA3 STUDY: FIRST EFFICACY/SAFETY REPORT OF LONG-TERM EXTENSION PERIOD WITH RILZABRUTINIB IN ADULTS WITH PERSISTENT/CHRONIC IMMUNE THROMBOCYTOPENIA (EHA 2025) - P3 | "Through multi-immune modulation, rilzabrutinib treatment during the LTE resulted in sustained platelet responses, as well as continued improvements in physical fatigue and bleeding scores. A high percentage of patients reduced or discontinued concomitant ITP therapy. Extended use of rilzabrutinib confers persistent efficacy, was well tolerated, and continued to have a favorable safety profile in patients with ITP."

Clinical • P3 data • Fatigue • Hematological Disorders • Immune Modulation • Immune Thrombocytopenic Purpura • Immunology • Pain • Thrombocytopenia • Thrombocytopenic Purpura

IMPACT OF RILZABRUTINIB ON BIOMARKERS OF INFLAMMATION AND COMPLEMENT FACTORS IN WARM AUTOIMMUNE HEMOLYTIC ANEMIA (WAIHA): RESULTS FROM THE PHASE 2 STUDY (EHA 2025) - P2 | "Rilzabrutinib has the potential to provide multi-immune modulation by not only reducing autoantibody production and immune complex consumption but also decreasing inflammation and complement activation, which have been implicated in amplifying RBC destruction in wAIHA. Further research is needed to better characterize the role of inflammation in wAIHA pathophysiology and the potential therapeutic effects of rilzabrutinib via inducing global anti-inflammation and multi-immune modulation."

Biomarker • P2 data • Anemia • Autoimmune Hemolytic Anemia • Cardiovascular • Fatigue • Hematological Disorders • Immune Modulation • Immunology • Inflammation • C1QA • ELANE • GFAP • ICAM1 • IFNG • IL10 • IL18 • IL1B • IL6 • MPO • NEFL • SELENOP • SELL • SELP • VCAM1

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

Next generation Bruton's tyrosine kinase inhibitors - characterization of in vitro potency and selectivity. (PubMed, Eur J Pharmacol) - "BTKi ranked in their selectivity as follows (most selective to least): remibrutinib, fenebrutinib, evobrutinib, orelabrutinib, rilzabrutinib and tolebrutinib. These data suggest that next generation BTKi show important differences in their in vitro target binding and selectivity when compared under the same conditions."

Journal • Preclinical • Allergy • Immunology

LONG-TERM EFFICACY AND SAFETY STUDY OF RILZABRUTINIB, ORAL BRUTON TYROSINE KINASE INHIBITOR, IN PATIENTS WITH WARM AUTOIMMUNE HEMOLYTIC ANEMIA (WAIHA): LUMINA PHASE 2B PART B (EHA 2025) - P2 | "Long-term rilzabrutinib showed sustained efficacy based on durable Hb response, decreased hemolytic markers, and clinically meaningful improvement in fatigue, and had a favorable safety profile in patients with wAIHA."

Clinical • P2b data • Anemia • Autoimmune Hemolytic Anemia • Back Pain • Complement-mediated Rare Disorders • Dermatology • Fatigue • Hematological Disorders • Immune Modulation • Immunology • Infectious Disease • Inflammation • Musculoskeletal Pain • Pain • Respiratory Diseases

CLINICAL FACTORS ASSOCIATED WITH RESPONSE TO RILZABRUTINIB, A BRUTON TYROSINE KINASE (BTK) INHIBITOR, IN PATIENTS WITH IMMUNE THROMBOCYTOPENIA (ITP) TREATED IN THE PHASE 3 LUNA3 STUDY (EHA 2025) - P3 | "The proportion of patients experiencing overall and sustained responses were higher for females vs males, baseline platelet counts ≥15x09/L vs <15x109/L, and no prior TPO-RA or rituximab use (Table). Consistent with previous analyses, univariate models indicated higher baseline platelet counts and being more treatment-naive to be associated with higher responses, suggesting a potential clinical benefit for starting rilzabrutinib in earlier lines of therapy. In multivariable models, higher baseline platelet counts emerged as an independent clinical factor associated with overall and sustained response to rilzabrutinib."

Clinical • P3 data • Fatigue • Hematological Disorders • Immune Modulation • Immune Thrombocytopenic Purpura • Immunology • Thrombocytopenia • Thrombocytopenic Purpura

A Study to Investigate the Efficacy and Safety of Rilzabrutinib in Adult Participants With Graves' Disease (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: Sanofi

New P2 trial • Endocrine Disorders • Grave’s Disease

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

Biological and target synthetic treatments for chronic spontaneous urticaria: A systematic review and network meta-analysis. (PubMed, Clin Transl Allergy) - "The findings of this study indicate that the biological agent omalizumab 300 mg and the oral small molecule remibrutinib at doses of 35 mg, 25 mg, or 10 mg are recommended for patients with antihistamine-refractory CSU."

Clinical • Journal • Retrospective data • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

Efficacy and Safety of Rilzabrutinib in Patients With Moderate-to-Severe Atopic Dermatitis: 16-Week Results From a Proof-of-Concept Phase II Clinical Trial. (PubMed, Br J Dermatol) - "This study did not meet its primary endpoint. However, consistent results favouring rilzabrutinib in itch response were observed. These findings also highlight the acceptable safety profile of rilzabrutinib vs the adverse effects associated with other BTK inhibitors."

Journal • P2 data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • Pruritus

Rilzabrutinib in Antihistamine-Refractory Chronic Spontaneous Urticaria: The RILECSU Phase 2 Randomized Clinical Trial. (PubMed, JAMA Dermatol) - P2 | "A total of 160 omalizumab-naive and omalizumab-incomplete responders were randomized (mean [SD] age, 44.1 [13.4] years; 112 [70.0%] female). Further research is needed to determine long-term efficacy and potential harms. ClinicalTrials.gov Identifier: NCT05107115."

Clinical • Journal • P2 data • Cardiovascular • Chronic Spontaneous Urticaria • Dermatology • Immunology • Pain • Urticaria

Rilzabrutinib: Regulatory submission in Japan for immune thrombocytopenic purpura in H2 2025 (Sanofi) - Q1 2025 Results: Regulatory decision in US/EU for immune thrombocytopenic purpura in H2 2025; Regulatory decision in China for immune thrombocytopenic purpura in 2026

China approval • EMA approval • FDA approval • Japan filing • Immune Thrombocytopenic Purpura • Immunology

Rilzabrutinib for the Treatment of Immune Thrombocytopenia. (PubMed, Eur J Haematol) - "We also offer a comparative assessment of other BTK inhibitors investigated for ITP and discuss rilzabrutinib's potential positioning relative to existing therapies, including thrombopoietin receptor agonists (TPO-RAs), rituximab, fostamatinib, and immunosuppressants. Preliminary data presented at ASH 2024 from the ongoing Phase 3 LUNA 3 trial, a randomized, double-blind study, further support rilzabrutinib's efficacy and long-term safety. If confirmed, these findings suggest that rilzabrutinib could represent a valuable therapeutic option for patients with refractory ITP, addressing a critical unmet need and potentially redefining treatment paradigms."

Clinical • Journal • Review • Cardiovascular • Hematological Disorders • Hepatology • Immune Thrombocytopenic Purpura • Immunology • Thrombocytopenia • Thrombocytopenic Purpura