rilzabrutinib (SAR444671) / Sanofi - LARVOL DELTA

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

Rilzabrutinib Shows Multiple Benefits for Patients With Immune Thrombocytopenia (Hematology Advisor) - P3 | N=232 | LUNA 3 (NCT04562766) | Sponsor: Principia Biopharma | "The primary outcome measure was a durable platelet response with counts of at least 50 x 109/L for at least two-thirds of 8 or more weekly platelet counts, without rescue therapy. Additional endpoints included the duration of the increased platelet counts, the use of rescue therapy, patient-reported outcomes, and bleeding scores...The results revealed sustained and clinically meaningful improvements in platelet counts, fatigue, and bleeding. Rilzabrutinib reduced by 52% the need for rescue therapy vs placebo, and the therapy improved fatigue in both responders and nonresponders. Adverse events were generally both low grade and manageable."

P3 data • Thrombocytopenia

Press Release: Rilzabrutinib granted orphan drug designation in the US for two rare diseases with no approved medicines (GlobeNewswire) - "The US Food and Drug Administration (FDA) has granted orphan drug designation to rilzabrutinib, an investigational, novel, advanced, oral, reversible Bruton’s tyrosine kinase (BTK) inhibitor, for two rare diseases, warm autoimmune hemolytic anemia (wAIHA) and IgG4-related disease (IgG4-RD)...Rilzabrutinib is currently under regulatory review in the US, the EU, and China for its potential use in immune thrombocytopenia (ITP). The target action date for the FDA regulatory decision for ITP, which was granted fast track designation, is August 29, 2025. Rilzabrutinib also received orphan drug designation for ITP in the US, EU, and Japan."

Filing • Orphan drug • PDUFA • Autoimmune Hemolytic Anemia • Immune Thrombocytopenic Purpura • Inflammation

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) - No abstract available

Clinical • P2 data • Inflammation

Safety and efficacy of rilzabrutinib vs placebo in adults with immune thrombocytopenia: the phase 3 LUNA3 study. (PubMed, Blood) - P3 | "Rilzabrutinib-- in ITP patients who failed multiple previous therapies (splenectomy, TPO-RA, rituximab and/or fostamatinib) resulted in rapid and durable platelet response, reduced rescue medication use and bleeding, significantly improved physical fatigue, and showed favorable safety. NCT04562766; EudraCT 2020-002063-60."

Journal • P3 data • Fatigue • Hematological Disorders • Immune Thrombocytopenic Purpura • Infectious Disease • Pneumonia • Respiratory Diseases • Thrombocytopenia • Thrombocytopenic Purpura

RNA Sequencing Analysis of Nasal Brushings From Participants Administered Rilzabrutinib 1200 MG Demonstrated an Impact on Multiple Pathways Relevant for Asthma (ATS 2025) - No abstract available

Asthma • Immunology • Respiratory Diseases

Reduction in the Use of Rescue Medication for Asthma Symptom Relief With Rilzabrutinib: Results From a Phase 2 Study (ATS 2025) - No abstract available

P2 data • Asthma • Immunology • Respiratory Diseases

Update on the Treatment of Chronic Spontaneous Urticaria. (PubMed, Drugs) - "About 70% of patients with antihistamine-refractory CSU do not reach complete control with omalizumab, the second-line treatment...Several emerging treatments can address these unmet needs including Bruton tyrosine kinase inhibitors, e.g., remibrutinib and rilzabrutinib; anti-KIT monoclonal antibodies, e.g., barzolvolimab; and anti-cytokine therapies, e.g., dupilumab...The most common adverse events were injection site reactions for dupilumab (12%), respiratory tract infections (11%), headache (6%), and petechiae (4%) for remibrutinib and changes in hair color (14%), neutropenia / decreased neutrophil count (9%) and skin hypopigmentation (1%) for barzolvolimab. This review provides an update on the current state of development of treatments for CSU."

Journal • Cardiovascular • Chronic Spontaneous Urticaria • Dermatology • Hematological Disorders • Immunology • Infectious Disease • Neutropenia • Pain • Respiratory Diseases • Urticaria

Efficacy, Safety and Pharmacokinetics of Rilzabrutinib in Patients With Warm Autoimmune Hemolytic Anemia (wAIHA) (clinicaltrials.gov) - P2 | N=22 | Active, not recruiting | Sponsor: Sanofi | Trial completion date: May 2025 ➔ Dec 2029

Trial completion date • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology

Sanofi treatment of autoimmune hemolytic anemia granted orphan status (Markets Insider) - "The FDA granted orphan designation to Sanofi (SNY) US Services’ rilzabrutinib as a treatment of autoimmune hemolytic anemia, according to a post to the agency’s website."

Orphan drug • Anemia

Rilzabrutinib Yields Responses in Angioedema in People With CS Urticaria (HCPLive) - P2 | N=161 | RILECSU (NCT05107115) | Sponsor: Sanofi | "Participants with moderate-to-severe chronic spontaneous urticaria (CSU) and angioedema treated with 1200mg of rilzabrutinib a day had greater improvements in their angioedema than those treated with placebo...These findings, from the phase 2 RILECSU trial (NCT05107115), will be presented at the 2025 American Academy of Allergy, Asthma, and Immunology (AAAAI)/World Allergy Organization (WAO) Joint Congress, February 28-March 3, in San Diego, California....The investigators found that at Week 12, a higher proportion of participants on rilzabrutinib 1200mg a day (60.9%) achieved AAS7 scores of 0 than placebo-treated participants (30.8%). Improvements were rapid, with 30.4% of participants on rilzabrutinib 1200mg a day reaching AAS7 scores of 0 at Week 1 compared with 3.8% of those on placebo. The proportion of participants with AAS7 scores of 0 was numerically higher every week through week 12 with rilzabrutinib 1200mg..."

P2 data • Chronic Spontaneous Urticaria

LUNA3: Study to Evaluate Rilzabrutinib in Adults and Adolescents With Persistent or Chronic Immune Thrombocytopenia (ITP) (clinicaltrials.gov) - P3 | N=232 | Active, not recruiting | Sponsor: Principia Biopharma, a Sanofi Company | Trial primary completion date: Jun 2025 ➔ Jan 2025

Trial primary completion date • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura

Effects of Rilzabrutinib on Angioedema over 12 Weeks: Results from the Phase 2 RILECSU Trial in Participants With Moderate-to-Severe Chronic Spontaneous Urticaria (AAAAI-WAO 2025) - P2 | "Within the omalizumab-naïve population (N=143), the effect of rilzabrutinib on angioedema was investigated in participants with angioedema at baseline (weekly Angioedema Activity Score [AAS7]>0; N=102). The duration of AAS7=0 response up to 12 weeks was greater with rilzabrutinib 1200mg/day vs placebo (5.1 weeks vs 3.1 weeks). Conclusions Rilzabrutinib 1200mg/day showed improvements in angioedema outcomes in participants with moderate-to-severe CSU compared to placebo in the RILECSU Phase 2 trial."

P2 data • Cardiovascular • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

Rilzabrutinib Improves Chronic Spontaneous Urticaria in Patients With and Without Allergic Comorbidities: A Subgroup Analysis From the RILECSU Study (AAAAI-WAO 2025) - P2 | "UAS7 experienced similar reductions. Conclusions CSU response to rilzabrutinib is observed regardless of type 2 inflammation and history of allergy."

Clinical • Allergic Rhinitis • Asthma • Atopic Dermatitis • Chronic Spontaneous Urticaria • Conjunctivitis • Dermatitis • Dermatology • Eosinophilic Esophagitis • Food Hypersensitivity • Gastrointestinal Disorder • Immunology • Inflammation • Nasal Polyps • Ocular Infections • Ocular Inflammation • Ophthalmology • Otorhinolaryngology • Respiratory Diseases • Sinusitis • Urticaria

Sanofi in partnership with Regeneron to present 24 abstracts across approved and investigational medicines at AAAAI Annual Meeting in San Diego (Pharmabiz) - "...Key presentations highlighting pivotal data from the Dupixent clinical program will be featured: LIBERTY-CSU CUPID phase 3 study: pooled results from Study A and Study C evaluating Dupixent in patients with moderate-to-severe CSU patients uncontrolled with H1-antihistamines; VESTIGE phase 4 study: new results evaluating improvements in small airway dysfunction in patients with uncontrolled moderate-to-severe asthma; NOTUS and BOREAS phase 3 studies: pooled results in adults with COPD and evidence of type 2 inflammation; LIBERTY EoE TREET phase 3 study: post-hoc analysis in adults and adolescents with EoE, with and without concurrent elimination diet...Immunology pipeline -- New data analyses will be presented from the RILECSU phase 2 study evaluating rilzabrutinib in adult patients with moderate-to-severe CSU, including: New results analyzing the effects of rilzabrutinib on angioedema over 12 weeks; Subgroup analysis assessing the effect of rilzabrutinib..."

Clinical data • Asthma • Chronic Obstructive Pulmonary Disease • Chronic Rhinosinusitis With Nasal Polyps • Chronic Spontaneous Urticaria • Eosinophilic Esophagitis

Rilzabrutinib: PDUFA action date for immune thrombocytopenia on Aug 29, 2025 (Sanofi) - Q4 & FY2024 Results: Regulatory decisions in EU/China for immune thrombocytopenia in H2 2025

China approval • EMA approval • PDUFA • Immune Thrombocytopenic Purpura • Immunology

Rilzabrutinib: "Primary endpoint demonstrated durable platelet response in 23% of patients compared to 0% at week 25 (95% CI, 16%-30%; p<0.0001)"; Immune thrombocytopenia (Sanofi) - Q4 & FY2024 Results

P3 data • Immune Thrombocytopenic Purpura • Immunology

Efficacy and Safety Results With Rilzabrutinib, an Oral Bruton Tyrosine Kinase Inhibitor, in Patients With Immune Thrombocytopenia: Phase 2 Part B Study. (PubMed, Am J Hematol) - P2 | "Rilzabrutinib continues to demonstrate durable platelet responses with favorable safety profile in previously treated ITP patients. Trial Registration: NCT03395210, EudraCT 2017-004012-19."

Journal • P2 data • Fatigue • Hematological Disorders • Immune Thrombocytopenic Purpura • Infectious Disease • Pain • Thrombocytopenia • Thrombocytopenic Purpura • Women's Health

RESULT: A Study to Evaluate the Efficacy and Safety of Frexalimab, SAR442970, or Rilzabrutinib in Participants Aged 16 to 75 Years With Primary Focal Segmental Glomerulosclerosis or Minimal Change Disease (clinicaltrials.gov) - P2 | N=84 | Recruiting | Sponsor: Sanofi | Initiation date: Aug 2024 ➔ Dec 2024

Trial initiation date • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Lupus Nephritis • Nephrology

Efficacy and Safety of Oral Bruton Tyrosine Kinase Inhibitor (BTKi) Rilzabrutinib in Adults with Previously Treated Immune Thrombocytopenia (ITP): A Phase 3, Placebo-Controlled, Parallel-Group, Multicenter Study (LUNA 3) (ASH 2024) - P3 | "In the rilzabrutinib arm, 1 patient with multiple risk-factors had a treatment-related grade 3 peripheral embolism (SAE) and 1 patient died due to pneumonia unrelated to treatment. Conclusion : Pivotal LUNA 3 phase 3 study results in patients with ITP showed that first-in-class BTKi rilzabrutinib has a robust therapeutic effect as shown by rapid and durable platelet response, reduced bleeding and need for rescue therapy, improved physical fatigue and QoL, and favorable safety and tolerability."

Clinical • P3 data • Fatigue • Hematological Disorders • Immune Thrombocytopenic Purpura • Infectious Disease • Pain • Pediatrics • Pneumonia • Respiratory Diseases • Thrombocytopenia • Thrombocytopenic Purpura

Improved Health-Related quality of Life (HRQoL) with Oral Bruton Tyrosine Kinase Inhibitor (BTKi) Rilzabrutinib Vs Placebo in Adults with Previously Treated Immune Thrombocytopenia (ITP): Phase 3 Luna 3 Multicenter Study (ASH 2024) - P3 | "Conclusion : Statistically significant and clinically meaningful improvement in physical fatigue was observed at weeks 13 and 25 with rilzabrutinib vs placebo, with improvements also seen in both durable and non-durable responders and other disease-specific HRQoL endpoints, indicative of potential multiple modalities of action. These HRQoL results provide additional evidence of rilzabrutinib's effects beyond increased platelet counts and reduced bleeding in previously treated adults with ITP."

Clinical • HEOR • P3 data • Fatigue • Hematological Disorders • Immune Thrombocytopenic Purpura • Pediatrics • 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

Part a Efficacy and Safety of Oral Bruton Tyrosine Kinase Inhibitor (BTKi) Rilzabrutinib in Patients with Warm Autoimmune Hemolytic Anemia (wAIHA): Multicenter, Open-Label, Phase 2b Study (ASH 2024) - P2 | "Conclusion : Rilzabrutinib in previously treated patients with primary wAIHA resulted in robust efficacy based on overall and durable Hb response, decreased hemolysis, and clinically meaningful improvement in fatigue. Rilzabrutinib was well-tolerated with a favorable safety profile in patients with wAIHA."

Clinical • P2b data • Anemia • Autoimmune Hemolytic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Immunology • Inflammatory Arthritis • Pain