Delving into the Latest Updates on Orelabrutinib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Obrutinib, abutinib

+ [2]

Target

BTK

Action

inhibitors

Mechanism

BTK inhibitors(Tyrosine-protein kinase BTK inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases+ [8]

Active Indication

Marginal Zone B-Cell LymphomaChronic Lymphocytic LeukemiaMantle-Cell Lymphoma+ [26]

Inactive Indication

Recurrent Central Nervous System LymphomaRefractory Central Nervous System LymphomaRefractory Follicular Lymphoma+ [1]

Originator Organization

Beijing InnoCare Pharma Tech Co., Ltd.

Active Organization

Beijing InnoCare Pharma Tech Co., Ltd.

Sun Yat-Sen University

WUXI APPTEC, INC

Inactive Organization

Biogen, Inc.Innocare Pharma Australia Pty Ltd

Drug Highest PhaseApproved

First Approval Date

China (25 Dec 2020),

Chronic Lymphocytic LeukemiaMantle-Cell LymphomaSmall Lymphocytic Lymphoma

RegulationConditional marketing approval (China), Special Review Project (China), Breakthrough Therapy (United States), Orphan Drug (United States), Priority Review (China)

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Structure/Sequence

Molecular FormulaC26H25N3O3

InChIKeyMZPVEMOYADUARK-UHFFFAOYSA-N

CAS Registry1655504-04-3

Marginal zone lymphoma (MZL) is a common type of indolent lymphoma that originates from the marginal zone of lymphoid follicles. This study aims to evaluate targeted therapy based on the prognostic risk stratification of MZL-IPI in newly diagnosed MZL cases requiring systemic treatment, and provides a basis for precision treatment of MZL.

Start Date21 Jan 2025

Sponsor / Collaborator

Ruijin Hospital

ChiCTR2400094533

/ SuspendedNot ApplicableIIT

Exploration of Determinants of Treatment Response to Orelabrutinib in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Prospective, Single-Arm, Multicenter, Phase 2 Study

Start Date24 Dec 2024

Sponsor / Collaborator

Second Affiliated Hospital Zhejiang University College of

NCT06701357

/ RecruitingPhase 2IIT

A Prospective, Open-label Phase II Study of Chidamide Plus R-CHOP + X in Previously Untreated Diffuse Large B-cell Lymphoma with Double Expression of MYC and BCL2.

This is a prospective, single-arm, open-label phase II clinical trial that evaluates the efficacy and safety of CR-CHOP regimen combined with different targeted drugs based on different molecular subtypes in newly diagnosed DEL patients.

Start Date10 Dec 2024

Sponsor / Collaborator

Ruijin Hospital

100 Clinical Results associated with Orelabrutinib

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100 Translational Medicine associated with Orelabrutinib

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100 Patents (Medical) associated with Orelabrutinib

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76

Literatures (Medical) associated with Orelabrutinib

01 Apr 2025·Bioorganic Chemistry

Design, synthesis and anti-tumor activity of BTK inhibitor Orelabrutinib derivatives

Article

Author: Qin, Xintong ; Zhao, Xiaomin ; Cai, Jin

Bruton tyrosine kinase (BTK), a non-receptor tyrosine kinase falling within the Tec kinase family, forms an essential part of the B cell receptor (BCR) signaling cascade. It has come to be regarded as a potential drug target for addressing a wide range of diseases, with a particular focus on hematopoietic malignancies and autoimmune disorders related to B lymphocytes. In the present study, by uncovering the binding mechanisms of the inhibitor Orelabrutinib with BTK, we identified four crucial structural elements requisite for the inhibition. Using scaffold hopping strategies, 28 novel derivatives belonging to the tricyclic and pyridine amide series were designed and synthesized from the lead compound Orelabrutinib. The outcomes revealed that 11a and 11k were able to effectively restrain the growth and migration of the tumor cell TMD8 upon comparing their in vitro activities, meriting further examination.

01 Feb 2025·eJHaem

Central nervous system posttransplant lymphoproliferative disorder following allogeneic hematopoietic stem cell transplantation successfully treated with combination therapy of acalabrutinib and immunochemotherapy: A case report and literature review

Article

Author: Zheng, Peihao ; Hu, Kai ; Zuo, Xiaona ; Ke, Xiaoyan ; Xu, Teng

AbstractHere, we report a case of Epstein‐Barr virus‐positive central nervous system‐post‐transplant lymphoproliferative disorder (CNS‐PTLD) patient who failed to achieve complete metabolic remission (CMR) after successively trying a methotrexate‐based regimen combined with orelabrutinib or whole‐brain radiotherapy and encountered intracranial hemorrhage during orelabrutinib treatment. Ultimately, the patient achieved CMR after one cycle of acalabrutinib in combination with temozolomide, teniposide, liposomal doxorubicin, dexamethasone, and rituximab (TEDDi‐R). Following another cycle of TEDDi‐R treatment, he has been receiving acalabrutinib maintenance up to now and remained in CMR. The case may provide an effective treatment option for CNS‐PTLD patients in clinical practice.

01 Feb 2025·Analytical and Bioanalytical Chemistry

Development, validation, and clinical application of LC-MS/MS method for simultaneous determination of ibrutinib, zanubrutinib, orelabrutinib, acalabrutinib, and their active metabolites in patients with B-cell lymphoma

Article

Author: Bing, Hao ; Zhao, Rongsheng ; Zhang, Xu ; Jiang, Dan ; Hu, Yang ; Xiong, Xin ; Song, Zaiwei ; Dong, Fei ; Ma, Yi

Bruton's tyrosine kinase inhibitors (BTKis) exhibit significant interindividual pharmacokinetics, making therapeutic drug monitoring (TDM) a promising approach for personalized therapy. However, simultaneous quantification of multiple BTKis poses technical challenges. A unified protocol for BTKis detection would be clinically desirable. Herein, we developed and validated a novel LC-MS/MS method for the simultaneous analysis of four BTKis including ibrutinib (IBR), zanubrutinib (ZAN), orelabrutinib (ORE), and acalabrutinib (ACB) and active metabolite of IBR and ACB (DIH and ACBM, respectively) in human plasma. The samples were prepared by liquid-liquid extraction using tert-butyl methyl ether. Ibrutinb-d4 (IS) was used as an internal standard. Chromatographic separation was obtained on an XBridge C18 column and connected to an LC-30AD system coupled to an API 4000⁺ mass spectrometer. The mobile phase comprised 10 mM ammonium acetate containing 0.1% formic acid and acetonitrile containing 0.1% formic acid. The optimized multiple reaction monitoring transitions of m/z 441.4 → 138.3, 475.4 → 304.2, 472.5 → 455.5, 428.3 → 411.5, 466.1 → 372.2, 482.2 → 388.4, and 445.5 → 142.5 were selected to inspect IBR, DIH, ZAN, ORE, ACB, ACBM, and IS, respectively. The method exhibited linearity from 1 to 1000 ng/mL (r > 0.99) for all analytes, with intra-day and inter-day precision of 1.8 to 9.7% and accuracy below 15%. Recovery ranged from 90.4 to 113.6%, and matrix effect varied from 89.3 to 111.0%. All compounds demonstrated stability under relevant conditions. Application of the method to 57 blood samples from 18 patients demonstrated high interpatient variability, with ORE plasma concentrations ranging from 25.6 to 89.9%. The validated LC-MS/MS method provides a feasible, specific, and rapid approach for quantification of BTKis in clinical settings. Simultaneous determination of four BTKis and their metabolites in a single extraction process and chromatographic run reduces analysis time, cost, and resources. The observed variability among individuals highlights the value of TDM for personalized treatment.

59

News (Medical) associated with Orelabrutinib

17 Feb 2025

·pipelinereview.com

InnoCare Announces the Approval of Registrational Phase III Study of BCL2 Inhibitor ICP-248 in Combination with Orelabrutinib as First-Line Therapy for Treatment of CLL/SLL Patients in China

BEIJING, China I February 17, 2025 I InnoCare Pharma (HKEX: 09969; SSE: 688428), a leading biopharmaceutical company focusing on the treatment of cancer and autoimmune diseases, announced today that the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA) has approved the registrational Phase III clinical trial of B-cell lymphoma-2 (BCL2) inhibitor ICP-248 (Mesutoclax) in combination with BTK inhibitor orelabrutinib as a first-line therapy for the treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) patients in China. ICP-248 (Mesutoclax) is a novel, orally bioavailable BCL2 selective inhibitor. BCL2 is an important regulatory protein in the apoptosis pathway, and its abnormal expression is associated with the development of various hematologic malignancies. ICP-248 exerts anti-tumor activity by selectively inhibiting BCL2 and restoring the normal apoptosis process in cancer cells. The fixed-duration treatment of ICP-248 in combination with orelabrutinib will provide deeper remission for treatment-naïve CLL/SLL patients without drug-resistant mutations, bringing hope of clinical cure to treatment-naïve CLL/SLL patients and becoming a treatment option with great potential. ICP-248, in combination with orelabrutinib, has demonstrated promising efficacy and a favorable safety profile in Phase II trial in treatment-naïve CLL/SLL patients. Market approval of the combination therapy will provide better treatment options for treatment-naïve CLL/SLL patients. Dr. Jasmine Cui, the co-founder, chairwoman and CEO of InnoCare, said, “ICP-248 is an important global asset in our hemato-oncology portfolio. We are rapidly advancing multiple clinical trials of ICP-248 globally, including the treatment of non-Hodgkin’s lymphoma, and acute myeloid leukemia (AML). Our hemato-oncology pipeline is designed for strong synergy, especially with the combination of BTK and BCL2 inhibitors, which has the potential to deliver improved outcomes for patients.” CLL/SLL, one of the most prevalent forms of leukemia, is an indolent malignancy of B lymphocytes. Globally, there are 191,000 newly diagnosed CLL cases each year, with 61,000 related deaths 1 . The incidence rate of CLL/SLL is on the rise in China 2 . Orelabrutinib has been approved for marketing in China and Singapore, and all three approved indications have been included in the National Reimbursement Drug List (NRDL) in China, including relapsed/refractory (r/r) CLL/SLL, r/r mantle cell lymphoma (MCL) and r/r marginal zone lymphoma (MZL). About InnoCare InnoCare is a commercial stage biopharmaceutical company committed to discovering, developing, and commercializing first-in-class and/or best-in-class drugs for the treatment of cancers and autoimmune diseases with unmet medical needs in China and worldwide. InnoCare has branches in Beijing, Nanjing, Shanghai, Guangzhou, Hong Kong, and the United States. 1 American Journal of Hematology 2 Frost & Sullivan SOURCE: InnoCare

Phase 2Drug ApprovalPhase 3INDClinical Result

21 Jan 2025

·www.fiercebiotech.com

InnoCare, Keymed sell ex-China rights for bispecific to RTW-built biotech in $520M deal

Chinese biotechs InnoCare Pharma and KeyMed Biosciences will also be in line for up to $502.5 million in potential milestone payments from Prolium Biosciences, along with tiered royalties on net sales.\n Chinese biotechs InnoCare Pharma and KeyMed Biosciences have sold the international rights to a clinical-stage bispecific antibody to a new company created by RTW Investments for $17.5 million in near-term cash.The CD20xCD3 antibody, known as ICP-B02 or CM355, is currently undergoing a phase 1/2 trial in China for relapsed/refractory non-Hodgkin lymphoma (NHL). That trial has already produced “promising early results in both intravenous (IV) and subcutaneous (SC) formulations, particularly in patients with follicular lymphoma (FL) and diffuse large B-cell lymphoma,\" the companies said in a Jan. 20 release.Specifically, all 13 patients who were treated with ICP-B02 at doses of 6 mg or above responded to their treatment, according to Innocare’s website. Innocare is best known for the BTK inhibitor orelabrutinib, which has been approved in China for lymphoma since 2023.A dose expansion trial pairing up ICP-B02 with other immunochemotherapies for earlier lines of NHL treatment is also in the works, with permission granted for a U.S. study. U.S.-based Prolium Biosciences has now agreed to pay InnoCare and Keymed $17.5 million in upfront and near-term payments to develop and commercialize ICP-B02 as a cancer drug outside of China. Prolium also has the right to develop ICP-B02 in non-cancer indications globally, according to a filling with the Hong Kong Stock Exchange (PDF).The two Chinese biotechs will also be in line for up to $502.5 million in potential milestone payments from Prolium, along with tiered royalties on net sales. InnoCare and KeyMed will split the money evenly, and will also receive a minority equity stake in Prolium.Prolium was set up by RTW in 2024. Last year also saw the New York-based investment fund involved in the launch of obesity biotech Kailera Therapeutics, which RTW said at the time was the fourth company it had helped create.It’s been a busy January for Keymed, which also launched a new company with U.S.-based biotech builder Mountainfield Venture Partners called Timberlyne Therapeutics to take forward a clinical-stage CD38-targeting antibody. Before that, Keymed was behind KYM, a joint venture with fellow Hong Kong-listed Lepu Biopharma that received $63 million from AstraZeneca in 2023 in turn for an early-phase antibody-drug conjugate.

License out/inImmunotherapyADCINDPhase 1

20 Jan 2025

·www.pharmaceutical-technology.com

AstraZeneca secures first BTK approval in first-line mantle cell lymphoma

Calquence is forecast to generate up to $4.7bn in sales by 2030, as per GlobalData intelligence. Credit: Nadezhda Fedrunova via Getty Images. AstraZeneca has received approval from the US Food and Drug Administration (FDA) for its Bruton’s tyrosine kinase (BTK) inhibitor, Calquence (acalabrutinib), for first-line use in mantle cell lymphoma (MCL). This approval makes Calquence the first BTK inhibitor available for adults with untreated MCL who are unsuitable for autologous haematopoietic stem cell transplantation (HSCT) and allows its use in combination with chemoimmunotherapy. The FDA granted approval based on data from the Phase III ECHO trial (NCT02972840). The randomised, double-blind, placebo-controlled study enrolled 598 patients aged 65 or older with untreated MCL who were unsuitable for HSCT. Patients were randomised to receive Calquence with chemotherapy bendamustine and Biogen and Genentech’s Rituxan (rituximab) or placebo plus bendamustine and Rituxan. Efficacy was measured by progression-free survival (PFS) and evaluated by an independent review committee. The median PFS was 66.4 months in the Calquence plus BR arm, compared to 49.6 months in the placebo plus bendamustine and Rituxan arm. The trial demonstrated a 27% improvement in PFS for Calquence over placebo. MCL is a rare and aggressive subtype of non-Hodgkin lymphoma, often diagnosed in later stages and characterised by the malignant transformation of B lymphocytes in the lymph node mantle zone. Calquence, a next-generation selective and irreversible BTK inhibitor, binds covalently to the BTK active site to inhibit enzymatic activity, suppressing the proliferation and survival of malignant B cells. AstraZeneca’s Calquence now holds a first-mover advantage in the treatment-naive MCL market, outpacing competitors such as BeiGene’s Brukinsa (zanubrutinib), Eli Lilly’s Jaypirca (pirtobrutinib), InnoCare’s Inokai (orelabrutinib), all of which remain in late-stage clinical trials for this indication. AbbVie and Johnson & Johnson’s (J&J’s) Imbruvica (ibrutinib) was previously positioned to lead the market but lost its accelerated approval in 2023 after the Phase III SHINE trial (NCT01776840) showed no overall survival benefit and a 7% increase in mortality risk for Imbruvica-treated patients. GlobalData projects that Calquence could generate up to $4.7bn in sales by 2030. With this FDA approval, AstraZeneca is poised to capitalise on its lead in the competitive BTK inhibitor market. GlobalData is the parent company of Pharmaceutical Technology.

Phase 3Drug ApprovalClinical ResultImmunotherapyAccelerated Approval

100 Deals associated with Orelabrutinib

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	L01XE	DB16272

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Marginal Zone B-Cell Lymphoma	China	Beijing InnoCare Pharma Tech Co., Ltd.	17 Apr 2023
Chronic Lymphocytic Leukemia	China	Beijing InnoCare Pharma Tech Co., Ltd.	25 Dec 2020
Mantle-Cell Lymphoma	China	Beijing InnoCare Pharma Tech Co., Ltd.	25 Dec 2020
Small Lymphocytic Lymphoma	China	Beijing InnoCare Pharma Tech Co., Ltd.	25 Dec 2020

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Waldenstrom Macroglobulinemia	NDA/BLA	China	Beijing InnoCare Pharma Tech Co., Ltd.	14 Mar 2022
Marginal zone lymphoma recurrent	Phase 3	China	Beijing InnoCare Pharma Tech Co., Ltd.	19 Dec 2023
Primary thrombocytopenia	Phase 3	China	Beijing InnoCare Pharma Tech Co., Ltd.	27 Oct 2023
Chronic idiopathic thrombocytopenic purpura	Phase 3	China	Beijing InnoCare Pharma Tech Co., Ltd.	26 Oct 2023
Purpura, Thrombocytopenic, Idiopathic	Phase 3	China	Beijing InnoCare Pharma Tech Co., Ltd.	16 Oct 2023
Macular Dystrophy, Corneal Type 1	Phase 3	China	Beijing InnoCare Pharma Tech Co., Ltd.	02 Nov 2022
Mediastinal large B-cell lymphoma	Phase 3	China	Beijing InnoCare Pharma Tech Co., Ltd.	02 Nov 2022
Mantle-Cell Lymphoma	Phase 3	United States	Beijing InnoCare Pharma Tech Co., Ltd.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASH2024 Manual	Not Applicable	Primary Central Nervous System Lymphoma First line	17	Orelabrutinib + Rituximab + Thiotepa	xlnhhrasft(xpkllqgzfi) = yopulvzqie sfkitycelc (kdomiqsrlc ) View more	Positive	09 Dec 2024
ASH2024 Manual	Not Applicable	Primary Central Nervous System Lymphoma First line	17	Orelabrutinib + Rituximab + Thiotepa + High-Dose Methotrexate	xlnhhrasft(xpkllqgzfi) = zstbdrqenn sfkitycelc (kdomiqsrlc ) View more	Positive	09 Dec 2024
ASH2024 Manual	Phase 2	Marginal Zone B-Cell Lymphoma Second line	12	Orelabrutinib 150 mg + Rituximab 375 mg/m²	kukqprndnb(jjxahxsxnj) = wvifpparqf fygzisutzc (arepkukqqt ) View more	Positive	09 Dec 2024
ASH2024 Manual	Not Applicable	Primary Central Nervous System Lymphoma First line	22	Orelabrutinib + Rituximab + Methotrexate	uquxynqftr(waauxbgulr) = glvhqvkxuu vivuuznzzh (lcvcpvejxl ) View more	Positive	09 Dec 2024
ASH2024 Manual	Not Applicable	Primary Central Nervous System Lymphoma	30	Orelabrutinib 150mg qdrituximab	(jxkrhdusbb) = vasbhvmiba ovpnkdlcvi (ttqrauylgb ) View more	Positive	09 Dec 2024
ChiCTR2400080207 (ASH2024) Manual	Phase 2	Lymphoplasmacytic Lymphoma \| Mantle-Cell Lymphoma \| Follicular Lymphoma \| Chronic Lymphocytic Leukemia \| Waldenstrom Macroglobulinemia \| Marginal Zone B-Cell Lymphoma \| Small Lymphocytic Lymphoma	64	Orelabrutinib 150 mg/day	(rqxbtqqdxc) = qlqfhkzycg bqxhosgear (ckfjhbuirs ) View more	Positive	09 Dec 2024
NCT05322733 (cwCLL-001, ASH2024) Manual	Phase 2	Chronic Lymphocytic Leukemia First line	25	Orelabrutinib+Fludarabine+Cyclophosphamide+Obinutuzumab	lsucjphulo(blffdxovdb) = fevryhuvfh yxeqyqmzrt (osmgtqvhqn ) View more	Positive	08 Dec 2024
ASH2024 Manual	Phase 2	Chronic Lymphocytic Leukemia \| Small Lymphocytic Lymphoma	29	Orelabrutinib + Rituximab/Orelabrutinib	fvrzjqtizq(omlaggtbku) = euoygbdcpv jatuohxmif (yyrncixnuy ) View more	Positive	08 Dec 2024
ASH2024 Manual	Not Applicable	Primary Central Nervous System Lymphoma First line	26	Rituximab, Methotrexate, Thiotepa, and Orelabrutinib	(mnhnebndxi) = grade 3 hematologic toxicity were observed in 30.77% patients, three patients with grade 4 hematologic toxicity. kfdhibnswq (skeynnsnsw )	Positive	07 Dec 2024
ASH2024 Manual	Not Applicable	Multi-Centric Castleman's Disease	10	Orelabrutinib	obzjlzwuyj(bqocgbffyt) = pmmpbsvhvx rsejvjyutk (hzwjeetauy ) View more	Positive	07 Dec 2024
ESMO2024	Not Applicable	Chronic Lymphocytic Leukemia	-	Orelabrutinib	(paqqowqcdf) = bnbjfaclmd jbkfexyuti (bbbdqpdbqk )	-	15 Sep 2024
ESMO2024	Not Applicable	Chronic Lymphocytic Leukemia	-	Orelabrutinib + chemotherapy	(paqqowqcdf) = nwxcymrahn jbkfexyuti (bbbdqpdbqk )	-	15 Sep 2024