Wayrilz (rilzabrutinib) / Sanofi - LARVOL DELTA

Rilzabrutinib for Chronic Immune Thrombocytopenia (ASH 2025) - No abstract available

Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura

Clinical Discussant for Chronic Immune Thrombocytopenia (ASH 2025) - "Discuss the clinical relevance of and possible applications for novel therapy in ITP (rilzabrutinib)"

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

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

Comparative effectiveness of second-line therapies for chronic immune thrombocytopenia: A network meta-analysis of RCTs (ASH 2025) - "The treatment groups were: Avatrombopag (96), Eltrombopag (283), Fostamatinib (101), Rilzabrutinib (133), Romiplostim (2116), and Rozanolixizumab (41)...Rituximab was analyzed indirectly and showed moderate efficacy... This NMA provides a comparative analysis of second-line therapies for chronic ITP, with Rozanolixizumab identified as the most effective treatment. Despite variability in safety profiles, all therapies demonstrated significant clinical benefits, supporting the adoption of personalized treatment strategies."

HEOR • Retrospective data • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura • SYK

Fatigue, hemoglobin, and inflammatory markers in warm autoimmune hemolytic anemia: Analysis from a phase 2b trial of rilzabrutinib (LUMINA2) (ASH 2025) - "Correlation of Hct changes with inflammatory markers and fatigue were measured and the relationship assessed. BTK inhibition shows a major effect on Hct and inflammatory markers in the treatment of wAIHA and shows great promise in addressing this disorder"

P2b data • Anemia • Autoimmune Hemolytic Anemia • Fatigue • Hematological Disorders • Immunology

Long-term efficacy and safety of rilzabrutinib, an oral bruton tyrosine kinase (BTK) inhibitor in patients with warm autoimmune hemolytic anemia (wAIHA) in the LUMINA Phase 2b part B study: A 74-week follow-up (ASH 2025) - P2 | "Extended follow-up of pts treated with rilzabrutinib showed continued efficacy with sustainedHb response, with some pts achieving drug-free remission; decreased hemolytic markers; clinicallymeaningful improvement in fatigue score; and a favorable safety profile in pts with wAIHA. Efficacy andsafety of rilzabrutinib will be further evaluated in a phase 3, randomized, placebo-controlled study(LUMINA3)."

Clinical • P2b data • Anemia • Autoimmune Hemolytic Anemia • Back Pain • Cardiovascular • Hematological Disorders • Immune Modulation • Immunology • Infectious Disease • Inflammation • Musculoskeletal Pain • Respiratory Diseases • Thrombosis

Early multi-immune modulation with rilzabrutinib in patients with primary ITP after first-line treatment failure: A phase 3b study (LUNA 4) (ASH 2025) - P3 | "The LUNA4 study will evaluate other outcomesincluding overall response (two PC at least 5 days apart of ≥50x109/L or ≥30x109/L and <50x109/L and atleast double from baseline without rescue therapy), cumulative number of weeks with platelet response,change from baseline in the immune thrombocytopenia bleeding scale score, proportion of participantsable to discontinue or reduce CS dose by 50% or to <5 mg from baseline, proportion of participantsachieving SROT, change from baseline in fatigue, levels of inflammatory markers, and frequency andseverity of treatment emergent adverse events. This study will evaluate the effect of early multi-immunemodulation with rilzabrutinib in ITP after failing 1L therapy and the ability of rilzabrutinib to modify ITPdisease progression."

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

A randomized, double-blind, placebo-controlled trial of a novel BTK inhibitor (rilzabrutinib) in patients with sickle cell disease (SCD) aged 10–65 years: LIBRA Study (ASH 2025) - P3 | "Additionally, participants may beon hydroxyurea and/or L-glutamine (if treated ≥6 months, on a stable dose ≥3 months, with ≥1 VOC whileon stable dose); those not receiving these medications must not plan to initiate them during the study.Key exclusion criteria include a history of stroke or abnormal transcranial doppler, and the use ofcrizanlizumab within 90 days and/or voxelotor within 30 days prior to screening. Other endpoints include change from baseline in QoL, patient globalimpression of fatigue and health status, and biomarkers (biomarkers of inflammation, endothelialactivation, and oxidative stress). This study aims to address a significant unmet need in SCD by evaluatingrilzabrutinib as a novel potential treatment option to reduce VOC burden and improve outcomes in SCD."

Clinical • Anemia • Autoimmune Hemolytic Anemia • Beta-Thalassemia • Cardiovascular • Genetic Disorders • Hematological Disorders • Immune Modulation • Immune Thrombocytopenic Purpura • Immunology • Inflammation • Sickle Cell Disease • Thrombocytopenic Purpura • Thrombosis • HBB

Impact of rilzabrutinib on gene-expression of inflammatory factors in patients with warm autoimmune hemolytic anemia who participated in the Phase 2B lumina 2 study (ASH 2025) - P2 | "In this study, elevated mRNA levels of inflammatory biomarkers were observed in pts withwAIHA compared with HVs suggesting an association between wAIHA and the activation of inflammatorycellular processes. C5 mRNA levels in pts with wAIHA were significantly diminished after 24 weeks ofrilzabrutinib treatment, indicating a reduction in complement activation; the reductions were morepronounced in responders. Although not significant after multiple adjustments, there was a trend ofSELENOP mRNA level reduction at week 24 of rilzabrutinib treatment with a more relevant decrease inresponders, suggesting regulation of oxidative stress and inflammation by rilzabrutinib."

Clinical • P2b data • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology • ELANE • ICAM1 • IL18 • MPO • SELENOP • TNFA

Reproductive health in patients with primary immune thrombocytopenia (ITP) receiving rilzabrutinib: A subgroup analysis from the Phase 3 LUNA3 multicenter study (ASH 2025) - P3 | "Meaningful improvements from baseline were observed in self-reported ITP-PAQ WRHitems in at-risk patients treated with rilzabrutinib during the LUNA3 DB period, especially for heavy andprolonged menstrual bleeding. These exploratory findings highlight rilzabrutinib's potential to improveHRQoL and bleeding outcomes for patients with ITP through multi-immune modulation. Larger studieson women's health outcomes and the potential impact of ITP treatments are needed."

Clinical • P3 data • Hematological Disorders • Immune Modulation • Immune Thrombocytopenic Purpura • Immunology • Thrombocytopenia • Thrombocytopenic Purpura • Women's Health • TINCR

Reduction in corticosteroid use with rilzabrutinib and sustained response in adults with persistent/chronic immune thrombocytopenia in the long-term extension period of the Phase 3 LUNA3 study (ASH 2025) - P3 | "In the LTE, 14 (20%) pts received rescue medication.Among 34 (49%) pts who entered the LTE on concomitant CS, 10 (29%) discontinued CS use (switched torilzabrutinib monotherapy), 2 (6%) reduced their CS ≥50% from DB baseline, and 6 (18%) reduced their CSdose to <5 mg (prednisone qd). Rilzabrutinib continued to demonstratefavorable safety profile in pts with ITP. These LTE findings support rilzabrutinib as an efficacious therapywith durable therapeutic effects and steroid-sparing potential, and underscores further the disease-modifying potential of multi-immune modulation in pts with ITP."

Clinical • P3 data • Hematological Disorders • Immune Modulation • Immune Thrombocytopenic Purpura • Immunology • Infectious Disease • Thrombocytopenia • Thrombocytopenic Purpura • PLAAT3

Improved health-related quality of life (HRQoL) and bleeding scores with oral bruton tyrosine kinase (BTK) inhibitor rilzabrutinib in the open-label (OL) period of the multicenter Phase 3 LUNA3 study in adults with immune thrombocytopenia (ITP) (ASH 2025) - P3 | "Additionally, patients who were initiallyon placebo and switched to rilzabrutinib during OL also experienced improvements in fatigue andHRQoL. These findings further support the use of rilzabrutinib in adults with ITP, highlighting its potentialto improve fatigue, HRQoL, and bleeding outcomes through multi-immune modulation."

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

Phase 3 Study to evaluate the efficacy and safety of rilzabrutinib in primary warm autoimmune hemolytic anemia (wAIHA): LUMINA 3 Study design (ASH 2025) - P2, P3 | "Key exclusion criteria includehistory of malignancy within 5 years; secondary wAIHA; active infections; prednisone >20mg/day or >10%dose change within 14 days; rituximab use within 12 weeks; and immunosuppressants within 30 days.After a 4-week screening period, approximately 90 participants will be randomized in a 2:1 ratio toreceive either oral rilzabrutinib or placebo BID during a 24-week DB period. In the LTE, participants with a CR sustained for ≥24 weeks may discontinuerilzabrutinib to assess off-treatment durability. If maintained for 24 weeks, they complete the EOS visitand withdraw; if Hb declines earlier, treatment may be resumed.This study aims to address a significant unmet need in patients with wAIHA by evaluating rilzabrutinib asa potential treatment option to improve Hb levels, reduce hemolysis, improve fatigue and overall QoL."

Clinical • P3 data • Anemia • Autoimmune Hemolytic Anemia • Cardiovascular • Hepatology • Immune Modulation • Immune Thrombocytopenic Purpura • Immunology • Infectious Disease • Pulmonary Disease • Thrombocytopenia • Thrombocytopenic Purpura

Fatigue, hemoglobin, and inflammatory markers in warm autoimmune hemolytic anemia: Analysis from a phase 2b trial of rilzabrutinib (LUMINA2) (ASH 2025) - P2 | "Rilzabrutinib treatment was associated with clinically meaningful within-patientimprovement in fatigue in wAIHA. The improvement was most pronounced in patients with durable Hbresponse but was also observed in a few non-responders. Weak-to-moderate correlation of FACIT-Fscores with Hb levels and moderate-to-strong negative correlation with inflammatory marker levelssuggests that mechanisms other than anemia, particularly chronic inflammation, may contribute tofatigue in wAIHA."

P2b data • Anemia • Autoimmune Hemolytic Anemia • Fatigue • Hematological Disorders • Immunology • IFNG • IL10 • TNFA

LUMINA 3 – wAIHA : A Phase 3, Two Arm Study, Assessing Efficacy, and Safety of Rilzabrutinib in Participants with Warm Autoimmune Hemolytic Anemia (wAIHA) (ASH 2025) - "Supported By Sanofi For in-person participants only"

Clinical • P3 data • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology

Discover a New Way Forward with WAYRILZ (ASH 2025) - "Supported By Sanofi For in-person participants onlyThis session includes a patient perspective"

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

LIBRA – SCD: A Randomized Placebo-Controlled Study Assessing Efficacy, and Safety of Rilzabrutinib in Participants with Sickle-Cell Disease (SCD) (ASH 2025) - "Supported By Sanofi For in-person participants only"

Clinical • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Bruton's tyrosine kinase inhibition in ITP: Wayrilz (rilzabrutinib) as a disease-modifying strategy. (PubMed, Ann Med Surg (Lond)) - "Incomplete responses, adverse effects, and relapses are the limitations of current treatments, which include corticosteroids, intravenous immunoglobulin, rituximab, and thrombopoietin receptor agonists. Clinical trials, including the key LUNA 3 trial, have shown good efficacy and safety, with durable platelet responses and minimal severe adverse events. This editorial examines rilzabrutinib's scientific justification, clinical data, comparative analysis, side effects, financial ramifications, and potential applications in the treatment of ITP."

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

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

Synthetic oxetanes in drug discovery: where are we in 2025? (PubMed, Expert Opin Drug Discov) - "While oxetanes feature famously in the taxol family, it was not until the recent approval of rilzabrutinib that they have been validated in a fully synthetic drug...The regulatory approval of rilzabrutinib and likely approval of ziresovir provide confidence in using oxetanes as important elements in drug design. While oxetanes have so far been incorporated primarily as pendant groups to optimize physicochemical properties, their use as scaffolding and binding elements presents an exciting opportunity. Enhanced synthetic accessibility to oxetane derivatives will expedite their inclusion in drug discovery campaigns."

Journal • Review • Oncology • Respiratory Diseases

Rilzabrutinib: First Approval. (PubMed, Drugs) - "In clinical trials, rilzabrutinib was associated with durable platelet responses in patients with previously treated immune thrombocytopenia. This article summarizes the milestones in the development of rilzabrutinib leading to its first approval for the treatment of adults with persistent or chronic immune thrombocytopenia who have had an insufficient response to previous treatment."

Journal • Asthma • Autoimmune Hemolytic Anemia • Chronic Spontaneous Urticaria • Dermatology • Genetic Disorders • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • Sickle Cell Disease • Thrombocytopenia • Thrombocytopenic Purpura • Urticaria

The Effects of Rilzabrutinib, an Oral Bruton Tyrosine Kinase Inhibitor, on Bleeding Symptoms and Health-Related Quality of Life in Patients with Immune Thrombocytopenia (ASH 2023) - P2 | "Prior ITP medication included CS (100%), TPO-RA (85%), immunosuppressants or IVIg (81%), and rituximab (50%). Overall, rilzabrutinib showed durable platelet responses, high compliance, and improvements on HRQoL measures in difficult to treat patients with relapsed ITP. There was no evidence of increased bleeding with rilzabrutinib. Clinically meaningful improvements in HRQoL were observed in multiple individual and overall HRQoL health domains following rilzabrutinib."

Clinical • HEOR • Cardiovascular • Fatigue • Hematological Disorders • Immune Thrombocytopenic Purpura • Infectious Disease • Thrombocytopenia • Thrombocytopenic Purpura • Thrombosis

Initial Report of Part B Phase 1/2 Efficacy and Safety Results for Bruton Tyrosine Kinase Inhibitor Rilzabrutinib in Patients with Relapsed Immune Thrombocytopenia (ASH 2023) - P2 | "Part B study results were consistent with part A. Rilzabrutinib demonstrated rapid, stable, and durable platelet responses in patients with relapsed ITP, with a favorable safety profile in part B."

Clinical • P1/2 data • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Infectious Disease • Thrombocytopenia • Thrombocytopenic Purpura

Bruton Tyrosine Kinase Inhibitor Rilzabrutinib Reduces Vaso-Occlusion and Markers of Inflammation and Adhesion in Transgenic Mice with Sickle Cell Disease (ASH 2024) - "There were no significant differences among treatment groups compared to vehicle for any red blood cell indices. Conclusion : Preclinical data provides evidence that treatment with rilzabrutinib ameliorates inflammation through multiple mechanisms of action and prevents microvascular stasis in Townes SCD mice."

Preclinical • Cardiovascular • Genetic Disorders • Hematological Disorders • Inflammation • Sickle Cell Disease • Thrombosis • CD31 • IL18 • IL1B • NLRP3 • PECAM1 • RELA • TLR4