Wayrilz (rilzabrutinib) / Sanofi - LARVOL DELTA

Properties of FDA-approved small molecule protein kinase inhibitors: a 2026 update. (PubMed, Pharmacol Res) - "The following ten drugs received FDA approval in 2025 - avutometinib (inhibiting MEK1/2 in serous ovarian carcinomas), defactinib (blocking FAK in low grade serous ovarian carcinomas), delgocitinib (antagonizing the JAK family in hand eczema), mirdametinib (inhibiting MEK1/2 in type I neurofibromatosis), remibrutinib (blocking BTK in chronic spontaneous urticaria), rilzabrutinib (antagonizing BTK in chronic immune thrombocytopenia), sunvozertinib (blocking mutant exon 21 insertion EGFR NSCLC), taletrectinib (inhibiting mutant ROS1 in NSCLC), vimseltinib (blocking CSF1R in tenosynovial giant cell tumors), and zongertinib (antagonizing mutant HER2 in NSCLC). This article summarizes the physicochemical properties of all 94 FDA-approved small molecule protein kinase inhibitors including the molecular weight, number of hydrogen bond donors/acceptors, ligand efficiency, lipophilic efficiency, polar surface area, and solubility. A total of 45 of the 94 FDA-approved drugs have a..."

FDA event • Journal • Review • Atopic Dermatitis • Chronic Spontaneous Urticaria • Contact Dermatitis • Dermatology • Genetic Disorders • Giant Cell Tumor of Bone • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Lung Cancer • Neurofibromatosis • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • Tenosynovial Giant Cell Tumor • Thrombocytopenia • Thrombocytopenic Purpura • Urticaria • CSF1R • EGFR • HER-2 • ROS1

Press Release: Sanofi’s rilzabrutinib designated breakthrough therapy in the US and orphan drug in Japan for the treatment of warm autoimmune hemolytic anemia (The Manila Times) - "Both designations are based on clinical data from the ongoing LUMINA 2 phase 2b study (clinical study identifier: NCT05002777) assessing the efficacy and safety of rilzabrutinib for patients with wAIHA. In addition, the new LUMINA 3 phase 3 study (clinical study identifier: NCT07086976), is assessing rilzabrutinib compared with placebo in patients with wAIHA."

Breakthrough therapy • Orphan drug • Autoimmune Hemolytic Anemia

2025: strong sales and EPS growth. (GlobeNewswire) - "ALTUVIIIO (haemophilia A) sales were €324 million of which 85% was in the US...Rest of World sales of €48 million benefited from the launches in Japan and Taiwan...Rezurock (chronic graft-versus-host disease) sales were €113 million and decreased by 6.1%...Sales in Europe were -€4 million, mainly from a one-time credit in the UK. In Rest of World, sales were €12 million, the overwhelming majority from the launch in China; Cablivi (acquired thrombotic thrombocytopenic purpura) sales were €69 million and increased by 1.4%, driven by more patients being treated in the US and Europe offset by an element of price impact in the US....Wayrilz (immune thrombocytopenia) sales were €6 million, all in the US, following approval in August 2025; Qfitlia (haemophilia A and B) sales were €4 million, all in the US, following approval in March 2025."

Sales • Chronic Graft versus Host Disease • Hemophilia A • Hemophilia B • Immune Thrombocytopenic Purpura

Wayrilz: Regulatory decision in Japan for immune thrombocytopenic purpura in H2 2026 (Sanofi) - Q4 & FY2025 Results

Japan approval • Immune Thrombocytopenic Purpura • Immunology

Immune thrombocytopenia: contemporary pathophysiology, treatment gaps, and the role of novel mechanisms in patient-centered care. (PubMed, Am J Manag Care) - P3 | "Rilzabrutinib targets several aspects of ITP disease pathophysiology by modulating multiple immune pathways. Approval was based on results from a phase 3 trial (LUNA 3 [NCT04562766]), in which patients with ITP who received rilzabrutinib demonstrated a rapid, durable platelet response and improvements in fatigue and bleeding with a tolerable safety profile."

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

104: Immune Thrombocytopenia: Management Strategies for the Medical Enigma (HOPA 2026) - "In addition to thrombopoietin receptor agonists (TPO-RAs) and the Syk inhibitor, fostamatinib, is the novel BTK inhibitor, rilzabrutinib, which was recently FDA approved for management of chronic ITP using a unique mechanism of action for ITP yet intimately familiar mechanism for most malignant hematology pharmacists.Management of ITP is tailored considering a multitude of patient-specific factors, but also Knowledge or Application Based: Coming soon! Learning Objectives: Coming Soon!"

Immune Thrombocytopenic Purpura • Immunology • Thrombocytopenia • Thrombocytopenic Purpura • SYK

Rilzabrutinib in immune thrombocytopenia: a targeted, patient-centered alternative to conventional therapies. (PubMed, Ann Med Surg (Lond)) - No abstract available

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

Press Release: Sanofi’s Wayrilz approved in the EU as the first BTK inhibitor to treat immune thrombocytopenia (The Manila Times) - "The EU approval of Wayrilz is based on the pivotal LUNA 3 phase 3 study (clinical study identifier: NCT04562766), in which Wayrilz met the primary and secondary endpoints, demonstrating a positive impact on sustained platelet counts as well as other ITP symptoms....Wayrilz has already been approved in the US and the United Arab Emirates (UAE), and it is currently under regulatory review for ITP in Japan and China."

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

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