A Multi-center, Open-label, Single-arm Study to Evaluate the Efficacy and Safety of Oral Rilzabrutinib in Adults With Immune Thrombocytopenia (ITP) Who Failed First-line Treatment

This is a multinational, open label, single arm study that will evaluate the impact of early multi-immune modulation with rilzabrutinib in adult ITP patients who failed first-line treatment. The study includes a screening period (up to 8 weeks), a primary analysis period (up to 28 weeks), a long-term extension period for selected participants (28 weeks) and a 24-week follow-up period only for eligible participants.

Start Date21 Jul 2025

Sponsor / Collaborator

Sanofi

NCT07086976

/ RecruitingPhase 3

A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study With an Open-label Period and Long-term Extension to Assess the Efficacy and Safety of Rilzabrutinib in Participants With Warm Autoimmune Hemolytic Anemia (wAIHA)

This is a parallel-group, Phase 3, double-blind, 2-arm study to investigate the efficacy, safety, PK and PD of oral rilzabrutinib in achieving durable Hb response (DHR) compared with placebo in approximately 90 male and female participants ? 18 years of age with a confirmed diagnosis of primary wAIHA.
Following a 4-week screening period, eligible participants will be randomized in a 2:1 ratio to receive rilzabrutinib or placebo in primary analysis period (PAP) for a duration of up to 24 weeks. All participants who completed PAP will then continue in open-label period (OLP) to receive rilzabrutinib for a duration of 28 weeks. Upon the completion of OLP, only participants who demonstrate Hb increase during the last 8 weeks of OLP per specified criteria in the protocol will be eligible to continue in long-term extension (LTE) of the study. The duration of the LTE period will be from the first-participant-in (FPI)-LTE until the last participant completes 52 weeks in LTE. The safety follow-up period of this study following treatment completion or discontinuation will be 2 weeks.

Start Date21 Jul 2025

Sponsor / Collaborator

Sanofi

NCT06975865

/ RecruitingPhase 3

A 52-week, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Group Sequential Study to Evaluate the Efficacy and Safety of Rilzabrutinib in Patients Aged 10 to 65 Years With Sickle-cell Disease

This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, group-sequential study (Part A), followed by an open-label LTE period (Part B) to investigate the efficacy, and safety of rilzabrutinib in participants with sickle-cell disease (SCD).
Study details include:
* Study duration: a 52-week double-blind period (Part A), followed by an open-label LTE period (Part B). Double-blind period has two parts, 50% (adult only) until the interim analysis (a proof-concept part analogous to a phase 2b study), and 50% (adult and children) after the interim analysis. Only the participants who complete double-blind treatment period (Part A) are eligible to continue to the LTE period. The duration of the LTE period (Part B) will be from the first-participant-in (FPI)-LTE (Part B) until the last participant who enters the LTE has completed 52 weeks.
* Treatment duration: 52-week double-blind period (Part A); LTE period (Part B) from the (FPI until the last participant who enters the LTE has completed 52 weeks.
* Visit frequency: Week visits based on the Schedule of Assessments.

Start Date07 Jul 2025

Sponsor / Collaborator

Sanofi

100 Clinical Results associated with Rilzabrutinib

100 Translational Medicine associated with Rilzabrutinib

100 Patents (Medical) associated with Rilzabrutinib

Literatures (Medical) associated with Rilzabrutinib

01 Sep 2025·EUROPEAN JOURNAL OF PHARMACOLOGY

Next generation Bruton's tyrosine kinase inhibitors – characterization of in vitro potency and selectivity

Article

Author: Angst, Daniela ; Cenni, Bruno ; Pulz, Robert

Bruton's tyrosine kinase (BTK) mediates B cell receptor and Fc receptor signaling and is a key regulator of autoimmunity and allergy. A series of novel BTK inhibitors (BTKi) are currently in development for non-oncologic indications with covalent-irreversible (remibrutinib, evobrutinib, tolebrutinib, orelabrutinib), covalent-reversible (rilzabrutinib), and non-covalent reversible (fenebrutinib) binding modes. This study characterizes their in vitro potency and selectivity profiles under the same conditions to minimize assay differences across the different binding modes. Covalent BTKi showed human in vitro blood BTK binding in a time- and concentration-dependent manner with remibrutinib being the most potent and fastest in onset of action. Cellular BTK pathway inhibition was determined in human blood B cells and basophils, and for covalent BTKi correlated well with BTK binding. In contrast to the covalent-irreversible remibrutinib, the non-covalent reversible fenebrutinib showed rapid loss of cellular BTK inhibition after washout. Kinase selectivity was assessed in a binding screen across the human kinome, followed by quantification of binding affinities for a selection of kinases. 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.

01 Jul 2025·EUROPEAN JOURNAL OF HAEMATOLOGY

Rilzabrutinib for the Treatment of Immune Thrombocytopenia

Review

Author: Vigna, Ernesto ; Manicardi, Veronica ; Labanca, Caterina ; Caridà, Giulio ; Morabito, Fortunato ; Gentile, Massimo ; Martino, Enrica Antonia ; Olivito, Virginia ; Mendicino, Francesco ; Bruzzese, Antonella ; Lucia, Eugenio ; Neri, Antonino ; Amodio, Nicola

ABSTRACT:

Advancements in the understanding of ITP pathogenesis have led to significant improvements in disease management through the use of both traditional immunosuppressive strategies and novel targeted therapies. However, a subset of patients remains refractory to treatment or achieves only transient benefits, underscoring the need for alternative therapeutic approaches. Bruton's tyrosine kinase (BTK) inhibitors have emerged as a promising strategy for autoimmune cytopenias, including ITP, due to their ability to modulate key immune pathways. Rilzabrutinib, an oral, reversible BTK inhibitor, represents a novel therapeutic approach for ITP. Rilzabrutinib, an oral, reversible BTK inhibitor, offers a novel mechanism of action by preserving platelet aggregation while reducing macrophage‐mediated platelet clearance, distinguishing it from irreversible BTK inhibitors. This review provides an updated and comprehensive analysis of the Phase 1/2 LUNA 2 trial and its long‐term extension, contextualizing rilzabrutinib within the broader treatment landscape. 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. Results from the phase 1/2 LUNA 2 trial and its long‐term extension demonstrated that Rilzabrutinib induced a durable platelet response in 40% of patients, with a median time to response of 11.5 days. The treatment exhibited a favorable safety profile, with predominantly grade 1 or 2 adverse events and no significant safety concerns commonly associated with BTK inhibitors, such as increased bleeding risk, hepatic toxicity, or cardiac arrhythmias. 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.

01 Jul 2025·JAMA Dermatology

Rilzabrutinib in Antihistamine-Refractory Chronic Spontaneous Urticaria

Article

Author: Ferrucci, Silvia ; Lucats, Laurence ; Mikol, Vincent ; Giménez-Arnau, Ana ; Gereige, Jessica ; Sun, Iris ; Mannent, Leda ; Ben-Shoshan, Moshe

Importance:

Chronic spontaneous urticaria (CSU) is a skin disease driven mainly by the activation of cutaneous mast cells through various mechanisms. Bruton tyrosine kinase (BTK), expressed in B cells and mast cells, plays a critical role in multiple immune-mediated disease processes.

Objective:

To determine the efficacy and risk profile of rilzabrutinib (SAR444671), an oral, reversible, covalent, next-generation BTK inhibitor, in treating patients with CSU.

Design, Setting, and Participants:

The Rilzabrutinib Efficacy and Safety in CSU (RILECSU) randomized clinical trial was a 52-week phase 2 study comprising a 12-week, double-blind, placebo-controlled, dose-ranging period, followed by a 40-week open-label extension. The trial was conducted from November 24, 2021, through April 23, 2024. Fifty-one centers enrolled and randomized participants across 12 countries in Asia, Europe, North America, and South America. The trial participants included adults aged 18 to 80 years with moderate to severe CSU (weekly Urticaria Activity Score [UAS7] of 16 or more; weekly Itch Severity Score [ISS7] of 8 or more) not adequately controlled with H1-antihistamine treatment.

Interventions:

Patients were randomized 1:1:1:1 to rilzabrutinib, 400 mg, once every evening (400 mg/d), twice per day (800 mg/d), 3 times per day (1200 mg/d), or matching placebo.

Main Outcomes:

The primary end point was change from baseline at week 12 in ISS7 (for US and US reference countries) or UAS7 (for non-US reference countries).

Results:

A total of 160 omalizumab-naive and omalizumab-incomplete responders were randomized (mean [SD] age, 44.1 [13.4] years; 112 [70.0%] female). The primary analysis population included only the 143 omalizumab-naive patients. Significant reductions at week 12 were observed with rilzabrutinib, 1200 mg/d, vs placebo from baseline in ISS7 (least squares [LS] mean, −9.21 vs −5.77; difference, −3.44 [95% CI, −6.25 to −0.62]; P = .02) and UAS7 (LS mean, −16.89 vs −10.14; difference, −6.75 [95% CI, −12.23 to −1.26]; P = .02). In addition, improvements in weekly Hives Severity Score (HSS7) and weekly Angioedema Activity Score (AAS7) were observed. Improvements in ISS7, UAS7, HSS7, and AAS7 were observed as early as week 1. CSU-related biomarkers, including soluble Mas-related G protein–coupled receptor X2, immunoglobulin (Ig)-G antithyroid peroxidase, IgG anti-Fc-ε receptor 1, and interleukin-31, were reduced compared to placebo at week 12. Rilzabrutinib demonstrated a favorable risk-benefit profile; adverse events occurring at a higher frequency with rilzabrutinib vs placebo included diarrhea, nausea, and headache.

Conclusions and Relevance:

The results of the RILECSU randomized clinical trial demonstrated efficacy and rapid onset of action of rilzabrutinib, 1200 mg/d, over 12 weeks, in addition to an acceptable adverse event profile. Together, these data support the use of rilzabrutinib in treating patients with moderate to severe CSU refractory to H1-antihistamines. Further research is needed to determine long-term efficacy and potential harms.

Trial Registration:

ClinicalTrials.gov Identifier: NCT05107115

News (Medical) associated with Rilzabrutinib

11 Aug 2025

·www.biospace.com

FDA Action Alert: Biogen/Eisai, Sanofi, Ionis and More

Taylor Tieden for BioSpace Arguably the FDA’s most anticipated decision this month is for a subcutaneous induction formulation of Biogen and Eisai’s Alzheimer’s drug Leqembi, which, according to Eisai, could “help reduce the burden on healthcare professionals and patients.” August is shaping up to be another busy and back-heavy month for the FDA, with at least eight target action dates lined up, including for some drugs that could open up completely new treatment pathways for rare diseases. Read below for more. Insmed Builds Up to First Bronchiectasis Approval New Jersey’s Insmed is proposing its oral DPP1 blocker brensocatib for the treatment of bronchiectasis, a chronic lung disease involving inflamed airways. The FDA is expected to decide on the matter on or before Aug. 12. If approved, brensocatib will be the first drug for bronchiectasis, and will open up the inhibition of DPP1 as a therapeutic mechanism. Insmed’s application is backed by the Phase III ASPEN study. Toplined in May 2024 , ASPEN showed that 10-mg brensocatib cut the annualized pulmonary exacerbation rate by 21.1% versus placebo. A 25 mg dose, meanwhile, led to a 19.4% drop. Brensocatib also hit the study’s secondary outcomes, including lung function, time to first exacerbation event and risk of exacerbations over 52 weeks. Tonix’s Fibromyalgia Drug Nears Verdict By Aug. 15, the FDA will release its decision on Tonix Pharmaceuticals’ non-opioid candidate TNX-102 SL, being proposed for the management of fibromyalgia. If it gets the go-ahead, TNX-102 SL would be the first therapy approved for this indication in more than 15 years, according to a March press release from the company. Designed to be taken orally via a tablet under the tongue, TNX-102 SL is a novel formulation of cyclobenzaprine hydrochloride, a non-opioid drug. Data from two pivotal trials, published in April, showed that the drug candidate can significantly reduce pain and elicit other clinical improvements, while also being tolerable. PTC Pushes Vatiquinone Forward in Friedrich’s Ataxia Despite Phase III Fail Fresh off the approval of its phenylketonuria therapy Sephience, PTC Therapeutics is approaching another decision date, this time for vatiquinone, an investigational drug for Friedreich’s ataxia. The FDA’s verdict is due Aug. 19. Vatiquinone is an investigational small-molecule drug that selectively blocks the 15-lipoxygenase enzyme, which regulates pathways involved in oxidative stress that are dysfunctional in Friedreich’s ataxia. The registration-directed late-stage MOVE-FA trial fell short of its primary endpoint, unable to significantly slow disease progression versus placebo. This study, nonetheless, formed part of PTC’s application for vatiquinone. Two long-term studies in pediatric and adult patients also support vatiquinone’s application. Ionis Targets HAE Prophylaxis Nod for Donidalorsen By Aug. 21, the FDA will release its decision on Ionis Pharmaceuticals’ proposal to use the RNA-targeting therapy donidalorsen to prevent attacks in patients with hereditary angioedema (HAE), a rare genetic disease that manifests as recurring episodes of severe swelling throughout the body. Ionis is backing its application with data from the Phase III OASIS-HAE and OASISplus trials. Data from the first trial, published in May 2024 , showed that monthly treatment with donidalorsen could cut HAE attacks by 81% versus placebo over a 25-week observation period. The second study, meanwhile, demonstrated that switching to donidalorsen from other prophylactics reduced the monthly HAE attack rate by 62%, as per a July readout . Donidalorsen works by reducing levels of the prekallikrein protein, which is involved in the inflammatory cascade. Outlook Eyes AMD Approval for New Avastin Formulation Outlook Therapeutics is advancing ONS-5010, an eye drop formulation of the anti-VEGF antibody bevacizumab—approved as an intravenous infusion under the brand name Avastin for various cancers—for the treatment of wet age-related macular degeneration. The FDA is scheduled to release its decision on Aug. 27. To support its regulatory application, Outlook conducted the Phase III NORSE EIGHT study, which in January showed that ONS-5010 could match Roche’s Lucentis in terms of improving visual acuity at 8 weeks. Retinal thickness, an indicator of anatomic response, was likewise comparable between patients treated with ONS-5010 and Lucentis. The FDA previously rejected ONS-5010, flagging in August 2023 a lack of evidence to support the drug’s efficacy. If approved, Outlook plans to market ONS-5010 under the brand name Lytenava. Precigen Anticipates First Approval in Recurrent Respiratory Papillomatosis Maryland’s Precigen is advancing the gene therapy PRGN-2012, also called zopapogene imadenovec, for the treatment of recurrent respiratory papillomatosis (RRP). The FDA is expected to render a verdict on Aug. 27. RRP is a rare and lifelong neoplastic lung disease affecting the upper and lower respiratory tract after HPV infection. Patients suffer from benign tumors growing in their air passages, causing voice hoarseness, difficulty swallowing and breathing problems. RRP can be fatal, according to Precigen, and there are currently no cures. PRGN-2012 induces the immune system to target cells infected with HPV 6 or HPV 11. Data from a pivotal Phase I/II study showed that the gene therapy can elicit more than a 50% complete response in RRP patients, while more than 85% of patients saw reductions in surgical interventions. If approved, PRGN-2012 will be the first treatment for RRP. Sanofi Targets Rare Disease Approval for Rilzabrutinib The FDA is currently reviewing Sanofi’s application for BTK inhibitor rilzabrutinib for the treatment of immune thrombocytopenia (ITP). A regulatory decision is expected on Aug. 29. ITP is a rare autoimmune disorder that manifests as low platelet counts arising from both heightened destruction and reduced production of platelets. Common symptoms include bruising and bleeding that, in more severe instances, can become life-threatening, such as in the case of intracranial hemorrhage. Rilzabrutinib, an orally available BTK blocker, helps address ITP by tamping down several inflammatory and immune pathways. Phase III data presented at the 2024 meeting of the American Society of Hematology last December showed that 65% of treated patients demonstrated platelet response , defined as a doubling of platelets from baseline and hitting a certain count threshold. This response was durable for at least eight of the last 12 weeks of the study in 23% of patients. Rilzabrutinib likewise resulted in bleeding improvements and lowered the need for rescue therapy versus placebo. Biogen, Eisai’s Subcutaneous Leqembi Could Reduce Treatment Burden The FDA will cap off the month with arguably its most closely watched regulatory action: A verdict , due on Aug. 31, for Biogen and Eisai’s proposed subcutaneous maintenance formulation of their anti-amyloid Alzheimer’s therapy Leqembi. If approved, the partners expect an under-the-skin delivery method could minimize the need for hospital visits and, in turn, “help reduce the burden on healthcare professionals and patients,” according to a February 2025 company presentation from Eisai. The companies are also planning a regulatory filing for a subcutaneous induction formulation of Leqembi next year. Data from the open-label extension phase of the Phase III Clarity AD study supported the subcutaneous application. Results in October 2023 showed that weekly injections under the skin were able to remove 14% more amyloid plaques than biweekly infusions. Subcutaneous Leqembi also appeared to be as safe as the intravenous formulation, with comparable rates of amyloid-related imaging abnormalities.

Phase 3Clinical ResultDrug Approval

03 Jun 2025

·www.globenewswire.com

Press Release: Rilzabrutinib granted orphan drug designation in the US for sickle cell disease

Rilzabrutinib granted orphan drug designation in the US for sickle cell disease Fourth orphan drug designation for rilzabrutinib in rare diseasesUnder regulatory review in the US, the EU, and China in immune thrombocytopenia Paris, June 3, 2025. 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. The FDA grants orphan drug designation to investigational therapies addressing rare medical diseases or conditions that affect fewer than 200,000 people in the US. Karin Knobe, MD, PhDGlobal Head of Development, Rare Diseases“Receiving our fourth orphan drug designation for rilzabrutinib reinforces our continued dedication to developing medicines to address the unmet medical needs of people living with rare diseases. People with sickle cell disease often live with severe episodes of pain from vaso-occlusive crises and other complications that can significantly impact both quality of life and life expectancy. There remains a need for novel treatment approaches to address these experiences by modulating the immune system responses that can contribute to sickle cell disease pathogenesis.” In addition to sickle cell disease, rilzabrutinib has received orphan drug designation for immune thrombocytopenia (ITP) in the US, the EU, and Japan, for warm autoimmune hemolytic anemia (wAIHA) in the US and the EU, and for IgG4-related disease (IgG4-RD) in the US. The safety and efficacy of rilzabrutinib have not been determined by any regulatory authority. Rilzabrutinib is currently under regulatory review in the US, the EU, and in China for its potential use in ITP. The target action date for the FDA regulatory decision for ITP, which was granted fast track designation, is August 29, 2025. Sickle cell disease supporting dataPreclinical data on sickle cell disease was presented at ASH 2024 showing that rilzabrutinib helped reduce vaso-occlusion –blockage of blood vessels – and inflammation in transgenic mice with sickle cell disease. About rilzabrutinib Rilzabrutinib is a novel, advanced, oral, reversible Bruton’s tyrosine kinase (BTK) inhibitor that has the potential to be an effective new medicine for several rare immune-mediated or inflammatory diseases by working to restore immune balance via multi-immune modulation. BTK, expressed in B cells, macrophages, and other innate immune cells, plays a critical role in multiple immune-mediated disease processes and inflammatory pathways. With the application of Sanofi’s TAILORED COVALENCY® technology, rilzabrutinib can selectively inhibit the BTK target while potentially reducing the risk of off-target side effects. About sickle cell diseaseSickle cell disease is a group of rare, genetic blood disorders in which red blood cells are misshapen, typically in a sickle or crescent shape, causing them to get stuck in small blood vessels, blocking blood flow. This can lead to episodes of severe pain as well as other health complications including infections, stroke, lung, eye, and kidney disease. Sickle cell disease affects more than 100,000 people in the US, approximately 90% of whom are African American and 3-9% of whom are Hispanic or Latino. Approximately 1 in 365 babies of African American descent born in the US have sickle cell disease, while an estimated 1 in 13 are carriers of the disease. People in the US with sickle cell disease have an estimated life expectancy that is 20 years shorter than average. About Sanofi Sanofi is an R&D driven, AI-powered biopharma company committed to improving people’s lives and creating compelling growth. We apply our deep understanding of the immune system to invent medicines and vaccines that treat and protect millions of people around the world, with an innovative pipeline that could benefit millions more. Our team is guided by one purpose: we chase the miracles of science to improve people’s lives; this inspires us to drive progress and deliver positive impact for our people and the communities we serve, by addressing the most urgent healthcare, environmental, and societal challenges of our time. Sanofi is listed on EURONEXT: SAN and NASDAQ: SNY Media RelationsSandrine Guendoul | +33 6 25 09 14 25 | sandrine.guendoul@sanofi.comEvan Berland | +1 215 432 0234 | evan.berland@sanofi.com Léo Le Bourhis | +33 6 75 06 43 81 | leo.lebourhis@sanofi.com Victor Rouault | +33 6 70 93 71 40 | victor.rouault@sanofi.com Timothy Gilbert | +1 516 521 2929 | timothy.gilbert@sanofi.com Investor RelationsThomas Kudsk Larsen |+44 7545 513 693 | thomas.larsen@sanofi.com Alizé Kaisserian | +33 6 47 04 12 11 | alize.kaisserian@sanofi.comFelix Lauscher | +1 908 612 7239 | felix.lauscher@sanofi.comKeita Browne | +1 781 249 1766 | keita.browne@sanofi.com Nathalie Pham | +33 7 85 93 30 17 | nathalie.pham@sanofi.comTarik Elgoutni | +1 617 710 3587 | tarik.elgoutni@sanofi.com Thibaud Châtelet | +33 6 80 80 89 90 | thibaud.chatelet@sanofi.comYun Li | +33 6 84 00 90 72 | yun.li3@sanofi.com Sanofi forward-looking statements This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts. These statements include projections and estimates and their underlying assumptions, statements regarding plans, objectives, intentions, and expectations with respect to future financial results, events, operations, services, product development and potential, and statements regarding future performance. Forward-looking statements are generally identified by the words “expects”, “anticipates”, “believes”, “intends”, “estimates”, “plans” and similar expressions. Although Sanofi’s management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Sanofi, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include among other things, the uncertainties inherent in research and development, future clinical data and analysis, including post marketing, decisions by regulatory authorities, such as the FDA or the EMA, regarding whether and when to approve any drug, device or biological application that may be filed for any such product candidates as well as their decisions regarding labelling and other matters that could affect the availability or commercial potential of such product candidates, the fact that product candidates if approved may not be commercially successful, the future approval and commercial success of therapeutic alternatives, Sanofi’s ability to benefit from external growth opportunities, to complete related transactions and/or obtain regulatory clearances, risks associated with intellectual property and any related pending or future litigation and the ultimate outcome of such litigation, trends in exchange rates and prevailing interest rates, volatile economic and market conditions, cost containment initiatives and subsequent changes thereto, and the impact that global crises may have on us, our customers, suppliers, vendors, and other business partners, and the financial condition of any one of them, as well as on our employees and on the global economy as a whole. The risks and uncertainties also include the uncertainties discussed or identified in the public filings with the SEC and the AMF made by Sanofi, including those listed under “Risk Factors” and “Cautionary Statement Regarding Forward-Looking Statements” in Sanofi’s annual report on Form 20-F for the year ended December 31, 2024. Other than as required by applicable law, Sanofi does not undertake any obligation to update or revise any forward-looking information or statements. All trademarks mentioned in this press release are the property of the Sanofi group. Attachment Press Release

Orphan DrugFast TrackImmunotherapyClinical Study

14 Apr 2025

·www.prnewswire.com

FDA Approval of Amgen's UPLIZNA for IgG4-related Disease Opens New Market Opportunity in Rare Autoimmune Segment | DelveInsight

With UPLIZNA receiving a label expansion that opens the door to a previously untapped rare disease market, Amgen is seeing strong returns on its USD 27.8 billion acquisition of Horizon Therapeutics. The drug has become the first to receive FDA approval specifically for treating immunoglobulin G4-related disease (IgG4-RD). LAS VEGAS, April 14, 2025 /PRNewswire/ -- IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory condition marked by the accumulation of IgG4-positive plasma cells in affected tissues, sometimes accompanied by elevated blood levels of IgG4. The disease can impact nearly any organ, with common sites including the pancreas, bile ducts, salivary and lacrimal glands, orbits, kidneys, lungs, and the retroperitoneal space. Due to its relatively recent identification, lack of widespread clinical awareness, and often subtle or slow-developing symptoms, IgG4-RD is likely underdiagnosed and underreported. It occurs more frequently in men, with most diagnoses in adults between their 30s and 50s, though cases have also been documented in children. In 2024, there were ~ 149K diagnosed prevalent cases of IgG4-RD across the 7MM, with the United States representing the largest share of these cases. In patients with IgG4-related disease, treatment may not always be necessary. In cases where individuals are asymptomatic, a watchful waiting approach can be appropriate. However, when vital organs are involved or symptoms are present, timely treatment becomes crucial, as IgG4-RD can lead to significant organ damage and dysfunction. Glucocorticoids are considered the first-line treatment, as outlined in the International Consensus Statement on IgG4-RD management. They typically produce rapid and substantial clinical improvement in both pancreatic and extra-pancreatic manifestations. To help maintain remission and reduce long-term steroid use, various glucocorticoid-sparing agents—such as azathioprine, mycophenolate mofetil, methotrexate, cyclophosphamide, and bortezomib—have been utilized across different organ systems, though their effectiveness varies. Steroid-sparing drugs like azathioprine, mycophenolate mofetil, and methotrexate are used to minimize the side effects of prolonged steroid therapy and support long-term disease control. However, the evidence supporting their efficacy remains limited. Rituximab has emerged as a promising newer option; it targets CD20-positive plasmablast precursors, leading to a reduction in plasmablasts and a subsequent decline in IgG4 production. To know more about IgG4-RD treatment options, visit @ New Treatment for IgG4-related Disease Recently, in April 2025, the FDA approved Amgen's anti-CD19 therapy, UPLIZNA, for the treatment of IgG4-related disease, making it the first and only approved treatment specifically for this condition, according to the company's announcement. This label expansion is supported by data from the Phase III MITIGATE trial, initially presented by Amgen in November 2024. The study showed that UPLIZNA reduced the risk of disease-related flares by 87% compared to placebo. Over the 52-week study period, only 7 out of 68 patients receiving UPLIZNA experienced flares, compared to 40 out of 67 in the placebo group—a difference Amgen highlighted as statistically significant. Additionally, 57.4% of patients treated with UPLIZNA achieved complete remission at the one-year mark versus just 22.4% of those on placebo. Nearly 90% of patients in the UPLIZNA arm were able to stop using glucocorticoids, compared to 37.3% in the placebo group. Within just 8 weeks of treatment, UPLIZNA recipients had a tenfold reduction in total glucocorticoid usage compared to placebo. Administered via intravenous infusion, UPLIZNA is a humanized monoclonal antibody that targets the CD19 protein found on specific immune cells. By binding to CD19, it depletes both immature and mature B cells, thereby addressing a key disease mechanism in IgG4-RD, which involves the widespread infiltration of B cells into affected tissues, leading to organ damage. Amgen recorded USD 379 million in UPLIZNA sales in 2024 from its original indication alone. However, the recent approval for IgG4-related disease presents a significant growth opportunity, as this new market includes a treatable patient population that is roughly twice as large as that for NMOSD. Learn more about the FDA-approved IgG4-RD drugs @ Drugs for IgG4-related Disease Treatment Apart from Amgen, key players such as Zenas Biopharma, Bristol Myers Squibb and Sanofi are also evaluating their lead candidates in different stages of clinical development, respectively. They aim to investigate their products to treat IgG4-RD. The treatment pipeline for IgG4-RD includes several promising therapies in advanced stages of development, such as ZB012 (obexelimab) and Rilzabrutinib, among others. These emerging treatments hold the potential to significantly improve patient outcomes and address existing gaps in care. Discover which therapies are expected to grab major IgG4-RD market share @ IgG4-related Disease Market Report Obexelimab (XmAb5871) is a dual-function monoclonal antibody that targets both CD19 and FcγRIIb—proteins found widely on B cells—aiming to suppress B-cell activity involved in various autoimmune disorders without destroying the cells. Its distinctive mechanism and subcutaneous self-injection format position it as a promising therapy to effectively address the role of B cells in chronic autoimmune conditions. Zenas is currently advancing obexelimab through multiple Phase II and III clinical trials for a range of autoimmune diseases, including IgG4-related disease, multiple sclerosis, systemic lupus erythematosus, and warm autoimmune hemolytic anemia. In August 2023, The Lancet Rheumatology published Phase II trial results showing its potential in treating IgG4-RD. These findings have led to an ongoing Phase III trial focused on evaluating the safety and efficacy of obexelimab via subcutaneous injection in patients with IgG4-RD. Rilzabrutinib (also known as PRN1008) is a selective, orally available, reversible covalent inhibitor of Bruton's Tyrosine Kinase (BTK), exhibiting a potent IC50 of 1.3 nM. It targets a cysteine residue on BTK, resulting in a slow dissociation rate—about 79% of BTK binding remains in peripheral blood mononuclear cells (PBMCs) 18 hours after the compound is washed out in vitro. This covalent binding is fully reversible upon denaturation of the protein. Functionally, rilzabrutinib suppresses anti-IgM-induced human B-cell proliferation and inhibits CD69 expression on B cells, with IC50 values of 5 ± 2.4 nM and 123 ± 38 nM, respectively, under 10% serum conditions. In August 2020, Sanofi entered into a definitive agreement to acquire Principia Biopharma, a deal approved unanimously by both companies' boards. The acquisition strengthened Sanofi's pipeline in immunology by integrating Principia's BTK inhibitors—including rilzabrutinib—into its broader strategy to develop next-generation therapies for autoimmune diseases. Discover more about drugs for IgG4-RD in development @ IgG4-related Disease Clinical Trials The anticipated launch of these emerging therapies for IgG4-RD are poised to transform the market landscape in the coming years. As these cutting-edge therapies continue to mature and gain regulatory approval, they are expected to reshape the IgG4-RD market landscape, offering new standards of care and unlocking opportunities for medical innovation and economic growth. DelveInsight estimates that the market size for IgG4-RD is expected to grow from USD 170 million in 2024, with a significant CAGR by 2034. This growth can be attributed to the approval of new therapies with improved safety and tolerability, which will significantly impact the treatment landscape in the coming years. DelveInsight's latest published market report, titled as IgG4-related Disease Market Insight, Epidemiology, and Market Forecast – 2034 , will help you to discover which market leader is going to capture the largest market share. The report provides comprehensive insights into the IgG4-RD country-specific treatment guidelines, patient pool analysis, and epidemiology forecast to help understand the key opportunities and assess the market's underlying potential. The IgG4-RD market report proffers epidemiological analysis for the study period 2020–2034 in the 7MM segmented into: Total Diagnosed Prevalent Cases of IgG4-RD Gender-specific Diagnosed Prevalent Cases of IgG4-RD Age-specific Diagnosed Prevalent Cases of IgG4-RD The report provides an edge while developing business strategies by understanding trends shaping and driving the 7MM IgG4-RD market. Highlights include: 10-year Forecast 7MM Analysis Epidemiology-based Market Forecasting Historical and Forecasted Market Analysis upto 2034 Emerging Drug Market Uptake Peak Sales Analysis Key Cross Competition Analysis Industry Expert's Opinion Access and Reimbursement Download this IgG4-RD market report to assess the epidemiology forecasts, understand the patient journeys, know KOLs' opinions about the upcoming treatment paradigms, and determine the factors contributing to the shift in the IgG4-RD market. Also, stay abreast of the mitigating factors to improve your market position in the IgG4-RD therapeutic space. Related Reports IgG4-related Disease Epidemiology IgG4-related Disease Epidemiology Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted IgG4-RD epidemiology in the 7MM, i.e., the United States, EU4 (Germany, Spain, Italy, and France), the United Kingdom, and Japan. IgG4-related Disease Pipeline IgG4-related Disease Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key IgG4-RD companies, including Amgen, Sanofi, Zenas Biopharma, Bristol-Myers Squibb, among others. Warm Autoimmune Hemolytic Anemia Market Warm Autoimmune Hemolytic Anemia Market Insights, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key wAIHA companies including ZENAS BIOPHARMA, JOHNSON & JOHNSON INNOVATIVE MEDICINE, NOVARTIS, MORPHOSYS, SANOFI, ALPINE IMMUNE SCIENCES , among others. Neuromyelitis Optica Market Neuromyelitis Optica Market Insights, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key neuromyelitis optica companies including Alexion Pharmaceutical, AstraZeneca , among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

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R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Purpura, Thrombocytopenic, Idiopathic	NDA/BLA	China	Sanofi Srl	30 Dec 2024
Purpura, Thrombocytopenic, Idiopathic	NDA/BLA	China	Genzyme Corp.	30 Dec 2024
Warm autoimmune hemolytic anemia	Phase 3	Japan	Sanofi	21 Jul 2025
Warm autoimmune hemolytic anemia	Phase 3	Denmark	Sanofi	21 Jul 2025
Warm autoimmune hemolytic anemia	Phase 3	Israel	Sanofi	21 Jul 2025
Anemia, Sickle Cell	Phase 3	United States	Sanofi	07 Jul 2025
Anemia, Sickle Cell	Phase 3	United Kingdom	Sanofi	07 Jul 2025
Pemphigus	Phase 3	United States	Principia Biopharma, Inc.	08 Jan 2019
Pemphigus	Phase 3	Argentina	Principia Biopharma, Inc.	08 Jan 2019
Pemphigus	Phase 3	Australia	Principia Biopharma, Inc.	08 Jan 2019

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05104892 (Phase 2 Study, ATS2025)	Phase 2	Asthma	196	Rilzabrutinib 800mg	gipcdbubaa(sfyhgfyuke) = knpngyvjph mincwjdqpe (ybnbzrjyfq )	Positive	16 May 2025
				Placebo	gipcdbubaa(sfyhgfyuke) = jbjtgdydcz mincwjdqpe (ybnbzrjyfq )
NCT05002777 (LUMINA 2, EHA2025)	Phase 2	Warm autoimmune hemolytic anemia	22	Rilzabrutinib 400 mg bid	vjaqgeqbxm(vobdzbeepq) = douxesrhlm vojwmkowqc (hcqmsddvso )	Positive	14 May 2025
				Concomitant CS + Rilzabrutinib	vjaqgeqbxm(vobdzbeepq) = nuuansmjap vojwmkowqc (hcqmsddvso )
NCT04562766 (LUNA3, EHA2025)	Phase 3	Purpura, Thrombocytopenic, Idiopathic	202	Rilzabrutinib 400 mg bid	ldnidjfjiz(noycevsezf) = ohsfyroxzo lhaygxevbq (zycdmlhnfo ) View more	Positive	14 May 2025
NCT04562766 (LUNA3, EHA2025)	Phase 3	Purpura, Thrombocytopenic, Idiopathic	174	Rilzabrutinib 400 mg bid	hebjfkrtdq(fdrnzhrjle) = uojpjhwxek fshdfcblid (rodwzpager ) View more	Positive	14 May 2025
NCT05107115 (RILECSU, Pubmed) Manual	Phase 2	Chronic Urticaria	160	rilzabrutinib 1200 mg/d	uelhfxcqmm(rjuibruuic) = zfgbysdxrf akzpevpvpf (xpyimsgqer ) View more	Positive	23 Apr 2025
				placebo	uelhfxcqmm(rjuibruuic) = ztadqchhgh akzpevpvpf (xpyimsgqer ) View more
NCT05002777 (ASH2024)	Phase 2	Warm autoimmune hemolytic anemia	-	Rilzabrutinib 400 mg bid	idhczbcgei(lmscoiualf) = 23% vjtmgdicsz (kacuvmdlnn ) View more	-	09 Dec 2024
				Concomitant CS
NCT04562766 (LUNA 3, ASH2024) Manual	Phase 3	Purpura, Thrombocytopenic, Idiopathic	202	rilzabrutinib	wpxitjdgtz(ucqozangiy) = katrobsngr xhsgmgjqtj (lojgqqeuzb ) Met View more	Positive	08 Dec 2024
				placebo	wpxitjdgtz(ucqozangiy) = nyookdrtdn xhsgmgjqtj (lojgqqeuzb ) Met View more
ASH2024	Not Applicable	Purpura, Thrombocytopenic, Idiopathic	-	Rilzabrutinib 400 mg bid	ebtuoflvjw(ybjwpsojbz) = rvfdsnntoi pupcqfxxku (tlikzcadio ) View more	-	08 Dec 2024
				Placebo	qvokzgrkgt(irmjcnoqjk) = zlbnndxved nqilmxcfjk (hmuprurvgd, 2.9) View more
NCT05104892 (ATS2024) Manual	Phase 2	Asthma	64	Rilzabrutinib 400 mg BID	iqfqbqqqpr(szlbcbzuka) = zgmwcqltwy rfbpxlbhqa (bhqisfqnuk ) View more	Positive	22 May 2024
NCT03395210 (LUNA 2, EHA2024) Manual	Phase 2	Purpura, Thrombocytopenic, Idiopathic Second line	71	Rilzabrutinib 400 mg bid	xzmayqtsqc(ewcicsnxbd) = uwqvzuenaq czsguhlwcp (ybzfoznkns ) View more	Positive	14 May 2024
				Rilzabrutinibhrombopoietin-receptor agonists (TPO-RA) or corticosteroids (CS)	pyqenysgzw(wtibondhdc) = hxmojqytdk oiyiddverg (onrntukjfq ) View more

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