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 Date15 Sep 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.

18 Aug 2025·BRITISH JOURNAL OF DERMATOLOGY

Efficacy and safety of rilzabrutinib in patients with moderate-to-severe atopic dermatitis: 16-week results from a proof-of-concept phase II clinical trial

Article

Author: Baret-Cormel, Lydie ; Valenzuela, Fernando ; Mikol, Vincent ; Tsianakas, Athanasios ; Kircik, Leon ; Nian, Gaowei ; Mannent, Leda

Abstract:

Background:

Atopic dermatitis (AD), the most common inflammatory skin disorder, carries a significant public health burden. Many patients with moderate-to-severe AD are unable to achieve adequate disease control with topical treatment and require treatment with oral immunosuppressants or monoclonal antibody injections. A continued unmet need for a safe, effective and easy-to-use oral drug exists. AD has a complex pathophysiology, including adaptive- and innate-dependent mechanisms, some of which involve Bruton tyrosine kinase (BTK). Rilzabrutinib is an oral, selective and reversible covalent BTK inhibitor.

Objectives:

To assess the efficacy and safety of rilzabrutinib in patients with moderate-to-severe AD and inadequate response or intolerance to topical corticosteroids.

Methods:

Eligible adults were enrolled in two staggered dose-regimen cohorts: 800 mg daily (400 mg twice daily) or 1200 mg daily (400 mg three times daily) and randomized 3 : 2 to receive rilzabrutinib or placebo for 16 weeks. The primary efficacy endpoint was percentage change in Eczema Area and Severity Index (EASI) score from baseline to week 16. Key secondary endpoints included the proportion of participants at week 16 achieving an Investigator’s Global Assessment score of 0 or 1, achieving EASI 75 and with a reduction in the weekly average of the daily Peak Pruritus Numerical Rating Scale (PP-NRS) of ≥ 4 from baseline. Safety was measured by recording adverse events (AEs).

Results:

The primary endpoint did not reach statistical significance [least squares mean difference vs. placebo: 800 mg –6.3% (P = 0.62); 1200 mg –3.9% (P = 0.67)]. The key secondary endpoints also did not demonstrate significant improvements with rilzabrutinib vs. placebo. However, a rapid improvement in absolute and relative change in weekly average of the daily PP-NRS was demonstrated with rilzabrutinib. Rilzabrutinib was well tolerated. Treatment-emergent AEs (TEAEs) were mostly mild, with a low incidence of serious AEs. TEAEs occurring at a higher frequency with rilzabrutinib than with placebo included nausea and diarrhoea. AEs associated with previous generations of BTK inhibitors were not seen with rilzabrutinib.

Conclusions:

This study did not meet its primary endpoint. However, consistent results favouring rilzabrutinib with regard to itch response were observed. These findings also highlight the acceptable safety profile of rilzabrutinib vs. the AEs associated with other BTK inhibitors.

11 Aug 2025·Immunotherapy

Evaluating rilzabrutinib in the treatment of immune thrombocytopenia.

Review

Author: Ghanima, Waleed ; Kuter, David J

There is an unmet need for newer treatment options in immune thrombocytopenia (ITP) that address its underlying complex immune dysregulation, induce durable platelet responses, are well tolerated, and improve fatigue and overall quality of life. Rilzabrutinib, an oral, reversible covalent Bruton tyrosine kinase (BTK) inhibitor, is effective through its multi-immune modulation mechanisms by inhibiting B-cell activation, possibly decreasing autoantibody production, preventing FcγR-mediated phagocytosis in the spleen and liver, and reducing chronic inflammation.Preclinical studies of rilzabrutinib in immune-mediated disease settings demonstrated high selectivity, full reversibility, and durable BTK occupancy. Oral rilzabrutinib 400 mg BID demonstrated rapid, durable platelet count increases in patients with persistent/chronic ITP in the phase 2 LUNA2 study and significantly improved durable platelet response vs placebo in the pivotal phase 3 LUNA3 trial. Additionally, rilzabrutinib improved multiple disease aspects including fatigue and bleeding with a well-tolerated safety profile.Through multi-immune modulation, rilzabrutinib achieves rapid and durable platelet response, improves fatigue, and decreases bleeding in ITP patients. It is well tolerated with an acceptable safety profile. Efficacy may be increased if administered earlier in the course of disease. Longer-term studies, and investigations in pediatric patients and other immune-mediated diseases are underway.

News (Medical) associated with Rilzabrutinib

30 Aug 2025

·firstwordpharma.com

Sanofi's oral BTK inhibitor greenlit for immune thrombocytopenia

Bolstering Sanofi's immunology and inflammation (I&I) growth aspirations, the FDA on Friday approved the French pharma's Wayrilz (rilzabrutinib) for adults with persistent or chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. The nod lends credence to Sanofi's $3.7-billion purchase of Principia Biopharma to gain the asset in 2020, as Wayrilz now represents a potential key growth driver for its I&I pipeline — an area the drugmaker is increasingly relying on for revenue as it slims down its oncology portfolio. For related analysis, see Vital Signs: Sanofi builds momentum for its I&I bets.An oral BTK inhibitor, Sanofi said Wayrilz can get at the root causes of ITP by targeting different pathways across the immune system."With its differentiated mechanism of action, Wayrilz has the potential to become a treatment of choice for immune thrombocytopenia patients who have not responded to a prior therapy," Brian Foard, Sanofi's head of specialty care, said in a company release. "Its multi-immune modulation approach shows promise in addressing the key drivers of immune thrombocytopenia, which aligns with Sanofi's commitment to adapting and evolving therapeutic solutions to help tackle ongoing unmet patient needs."Durable platelet responseThe approval was based on results from the Phase III LUNA 3 study, which were toplined last April before being shared in more detail at last year's American Society of Hematology (ASH) meeting. The 202-patient study compared twice-daily oral Wayrilz against placebo. The BTK inhibitor met the trial's primary endpoint of durable platelet response, with 23% of patients who received the therapy achieving platelet counts at or above 50,000/μL for at least eight out of the last 12 weeks of the 24-week blinded treatment period in the absence of rescue therapy, compared with zero patients in the placebo group. Additionally, Wayrilz reduced the need for rescue therapy by a significant 52% versus placebo, and also led to significant and clinically meaningful improvements in physical fatigue and bleeding. The most common treatment-related adverse events were diarrhoea (23%), nausea (17%), headache (8%) and abdominal pain (6%).Feedback from experts suggest Wayrilz is likely to become a go-to second-line option after thrombopoietin receptor agonists, with the potential to quickly gain traction due to physician familiarity with BTK inhibitors such as Imbruvica (ibrutinib) in blood cancers. However, Sanofi has plenty of competition nipping at its heels from Novartis' BAFF-R antibody ianalumab and several anti-CD38 mAbs. For further analysis, see KOL Views Q&A: Sanofi's rilzabrutinib can contend in ITP but competition fierce and more footsteps approaching.Outside the US, Wayrilz is under regulatory review in the EU and China.

Clinical ResultDrug ApprovalPhase 3ImmunotherapyAcquisition

29 Aug 2025

·endpoints.news

FDA approves BTK inhibitor that’s key to Sanofi’s immunology strategy

The FDA approved Sanofi’s BTK inhibitor that the French drugmaker acquired in its $3.7 billion buyout of Principia Biopharma. The company said Friday that the regulators cleared rilzabrutinib in a rare disease called immune thrombocytopenia, or ITP. The drug is branded as Wayrilz. The wholesale acquisition cost for Wayrilz will be $17,500 a month, which is before discounts, rebates or patient assistance programs, a Sanofi spokesperson said. Wayrilz is part of a larger effort at Sanofi to become the leading immunology pharma company. Sanofi has unveiled or acquired a handful of programs targeting immunological conditions in recent years, and the company expects Wayrilz to produce between €2 billion and €5 billion in annual peak sales. So far, Sanofi’s strategy hasn’t always led to success. The company was forced to shelve studies of another drug from Principia called tolebrutinib in 2023 after trials were put on hold . The drug continued to be dogged by safety concerns despite positive efficacy results in a multiple sclerosis trial that read out last year. Tolebrutinib had been Principia’s lead drug at the time Sanofi acquired the company in 2020. Another program called itepekimab underwhelmed in a COPD study earlier this year. And even the path for Wayrilz has been bumpy. The drug failed an atopic dermatitis study in 2023. Sanofi’s immunology pipeline also includes amlitelimab, an OX40L drug from Kymab that’s currently in Phase 3 studies for atopic dermatitis; lunsekimig, an anti-IL-13/TSLP program with a Phase 2 readout in asthma expected next year; and frexalimab, a CD40L-targeting therapy that’s expecting Phase 2 lupus data in the second half of 2026. “Our current and evolving portfolio within immunology and immunoscience more broadly really explores the multifaceted nature of key neurologic nodes within the immune system,” Sanofi CSO Mike Quigley told Endpoints News in an interview ahead of the decision. As for Wayrilz, ITP is a rare autoimmune disorder that leads to low platelet counts and an increased risk of bleeding and bruising. Quigley estimates there are about 100,000 ITP patients in the US. In addition to ITP, Sanofi is continuing to study Wayrilz in asthma, chronic hives, IgG4-related disease and other rare diseases, though these studies are early and no readouts are expected until 2027. Editor’s note: This story was updated to add the drug’s wholesale acquisition cost.

ImmunotherapyAcquisitionPhase 3Drug ApprovalPhase 2

16 Aug 2025

·www.globenewswire.com

Sanofi’s rilzabrutinib earns orphan designation in the EU for IgG4-related disease

Sanofi’s rilzabrutinib earns orphan designation in the EU for IgG4-related disease Data from the positive Phase 2 study evaluating rilzabrutinib for the treatment of IgG4-related disease presented at EULAR 2025 Additional orphan designation underscores Sanofi commitment to advancing new medicines in immune-mediated rare diseases August 14, 2025. The European Medicines Agency has granted orphan designation to rilzabrutinib, a reversible covalent Bruton’s tyrosine kinase (BTK) inhibitor, for IgG4-related disease (IgG4-RD). EMA grants orphan designation to investigational therapies addressing rare, life-threatening or debilitating medical diseases or conditions that affect no more than 5 in 10,000 persons in the EU. Rilzabrutinib for the treatment of IgG4-related disease was evaluated in a phase 2 study (clinical study identifier: NCT04520451) and results were presented at the European Alliance of Associations for Rheumatology (EULAR) 2025 Congress. In IgG4-RD patients, treatment with rilzabrutinib for 52 weeks led to reduction in disease flare, other disease markers, and glucocorticoid sparing. The safety profile of rilzabrutinib in the study was consistent with previous studies, with no new safety signals observed. In addition to IgG4-related disease, rilzabrutinib has received orphan designations for immune thrombocytopenia (ITP) in the US, the EU, and Japan; and for warm autoimmune hemolytic anemia, IgG4-RD and sickle cell disease in the US. Rilzabrutinib has also been granted fast track designation in the US in ITP and IgG4-RD. Rilzabrutinib is currently under regulatory review in the US, the EU, and China for its potential use in ITP. The target action date for the US FDA regulatory decision for ITP, which was granted fast track designation, is August 29, 2025. Rilzabrutinib is an investigational agent, and its safety and efficacy have not been evaluated by any regulatory authority. Rilzabrutinib is a novel, advanced, oral, reversible covalent 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 the TAILORED COVALENCY® technology, rilzabrutinib can selectively inhibit the BTK target while potentially reducing the risk of off-target side effects. IgG4-RD is a progressive, relapsing, chronic immune-mediated rare disease, which can manifest in almost every organ and can lead to organ damage and irreversible dysfunction with a sometimes-fatal outcome. People with IgG4-RD experience frequent flare-ups of the condition characterized by periods of exacerbated symptoms. It affects approximately eight out of 100,000 adult patients in the US each year. Due to its rarity and challenges with diagnosis, the global prevalence of IgG4-RD is unknown. Sanofi is an R&D driven, AI-powered biopharma company committed to improving people’s lives and delivering 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. The content above comes from the network. if any infringement, please contact us to modify.

Orphan DrugFast TrackClinical ResultImmunotherapy

100 Deals associated with Rilzabrutinib

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KEGG	Wiki	ATC	Drug Bank
D11873	-	-	-

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Purpura, Thrombocytopenic, Idiopathic	United States	Genzyme Corp.	29 Aug 2025

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
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
Pemphigus	Phase 3	Brazil	Principia Biopharma, Inc.	08 Jan 2019
Pemphigus	Phase 3	Bulgaria	Principia Biopharma, Inc.	08 Jan 2019

Clinical Result

Indication

Phase

Evaluation

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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	dpkzkyhopa(vkelsubekx) = jsnasdbznp benwhetlaf (ebmqwlmywg )	Positive	16 May 2025
				Placebo	dpkzkyhopa(vkelsubekx) = sunadvlupa benwhetlaf (ebmqwlmywg )
NCT05002777 (LUMINA 2, EHA2025)	Phase 2	Warm autoimmune hemolytic anemia	22	Rilzabrutinib 400 mg bid	iprfzzqvxl(zpomtwxzyk) = fxyzstbtpz kcthxculfc (zriepixkpn )	Positive	14 May 2025
				Concomitant CS + Rilzabrutinib	iprfzzqvxl(zpomtwxzyk) = kwokorjqqs kcthxculfc (zriepixkpn )
NCT04562766 (LUNA3, EHA2025)	Phase 3	Purpura, Thrombocytopenic, Idiopathic	174	Rilzabrutinib 400 mg bid	drbktlbyje(jgpohvoygv) = bsciqcafcs shijexxljc (mpgnmaicmr ) View more	Positive	14 May 2025
NCT04562766 (LUNA3, EHA2025)	Phase 3	Purpura, Thrombocytopenic, Idiopathic	202	Rilzabrutinib 400 mg bid	xziwopnjfl(vmfevujklj) = rqajuwjzxo cpfwmaeewf (cgqqpokwqe ) View more	Positive	14 May 2025
NCT05107115 (RILECSU, Pubmed) Manual	Phase 2	Chronic Urticaria	160	rilzabrutinib 1200 mg/drilzabrutinib 1200 mg/d	jgzumutkpw(alimjcouqw) = zydhcfzmwl tjqxtqobzc (jxvuwlejqo ) View more	Positive	23 Apr 2025
				placebo	jgzumutkpw(alimjcouqw) = nwwlsydulb tjqxtqobzc (jxvuwlejqo ) View more
NCT05002777 (ASH2024)	Phase 2	Warm autoimmune hemolytic anemia	-	Rilzabrutinib 400 mg bid	rlzoxfweqa(hdevppfrlv) = 23% jvkqcqponw (vjxlafxeoz ) View more	-	09 Dec 2024
				Concomitant CS
NCT04562766 (LUNA 3, ASH2024) Manual	Phase 3	Purpura, Thrombocytopenic, Idiopathic	202	rilzabrutinib	hvnrcvqzag(igczqeuypq) = lsttamiakz lkberpsypq (pmtmeovnzt ) Met View more	Positive	08 Dec 2024
				placebo	hvnrcvqzag(igczqeuypq) = aolvfpqptc lkberpsypq (pmtmeovnzt ) Met View more
ASH2024	Not Applicable	Purpura, Thrombocytopenic, Idiopathic	-	Rilzabrutinib 400 mg bid	tkvfnfpbjc(ykkzuylwwc) = ymqlvefbvm pshwncyxzr (nqsrokzzch ) View more	-	08 Dec 2024
				Placebo	gwacbaafyi(actikegvoj) = egrmttxsxt ommblojzgl (bhvvrskvrs, 2.9) View more
NCT05104892 (ATS2024) Manual	Phase 2	Asthma	64	Rilzabrutinib 400 mg BID	dbilzpovkj(vbehujkyuv) = uvzslpdmnu bqgrzkxkpj (mvkkygmcqh ) View more	Positive	22 May 2024
NCT03395210 (LUNA 2, EHA2024) Manual	Phase 2	Purpura, Thrombocytopenic, Idiopathic Second line	71	Rilzabrutinib 400 mg bid	byjsrdtefr(dqzqkgaiyl) = mzveaulvoz ygieeulbou (klwdbkuzmm ) View more	Positive	14 May 2024
				Rilzabrutinibhrombopoietin-receptor agonists (TPO-RA) or corticosteroids (CS)	rpkzylfhqk(gzkbpryozz) = wbptkgmxdz qntrwzvrqi (ytaqqphrwj ) View more

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