Delving into the Latest Updates on Vodobatinib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

+ [3]

Target

Bcr-Abl

Action

inhibitors

Mechanism

Bcr-Abl inhibitors(Bcr-Abl tyrosine kinase inhibitors)

Therapeutic Areas

NeoplasmsHemic and Lymphatic DiseasesImmune System Diseases+ [1]

Active Indication

Philadelphia chromosome positive chronic myelogenous leukemiarefractory chronic myelocytic leukemiaChronic phase chronic myeloid leukemia+ [2]

Inactive Indication

Lewy Body DiseaseYoung onset Parkinson disease

Originator Organization

Sun Pharma Advanced Research Co. Ltd.

Active Organization

Sun Pharma Advanced Research Co. Ltd.

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

RegulationOrphan Drug (European Union)

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Structure/Sequence

Molecular FormulaC27H20ClN3O2

InChIKeyZQOBVMHBVWNVBG-UHFFFAOYSA-N

CAS Registry1388803-90-4

This study evaluates the safety and tolerability of treatment with K0706 in Dementia with Lewy Bodies (DLB).
The hypothesis is that K0706 will be safe and tolerable and that this drug will alter CSF and plasma biomarkers in DLB. Clinical assessments of cognitive, behavioral and motor functioning will also be evaluated. A total of 45 participants will be randomized 1:1:1 into 3 groups (n=15/per group) to be treated with sachet of 192 mg powder of K0706 ( equivalent to 96 mg capsule of K0706) or sachet of 384 mg powder of K0706 (equivalent to 192 capsule of K0706) or sachet of matching placebo ( equivalent to a capsule of placebo) for 12 weeks, followed by 4-week wash-out period.

Start Date05 Sep 2019

Sponsor / Collaborator

Georgetown University

[+1]

NCT03655236

/ TerminatedPhase 2

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of K0706 in Subjects With Early Parkinson's Disease

This study consists of 2 parts. Part 1 of the study is conducted to evaluate the efficacy, safety, and tolerability of two doses of K0706 compared to placebo in subjects with early Parkinson's Disease who are not receiving dopaminergic therapy. Part 2 is an optional long term extension study for subjects who have completed week 40 of Part 1

Start Date18 Feb 2019

Sponsor / Collaborator

Sun Pharma Advanced Research Co. Ltd.

100 Clinical Results associated with Vodobatinib

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100 Translational Medicine associated with Vodobatinib

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100 Patents (Medical) associated with Vodobatinib

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13

Literatures (Medical) associated with Vodobatinib

01 Mar 2025·The Lancet Haematology

Vodobatinib for patients with Philadelphia chromosome-positive chronic myeloid leukaemia resistant or intolerant to multiple lines of previous therapy: an open-label, multicentre, phase 1/2 trial

Article

Author: Apte, Shashikant ; Yao, Siu-Long ; Charbonnier, Aude ; Tantravahi, Srinivas K ; Chimote, Geetanjali ; Popov, Viola M ; Hannah, Guy ; Illés, Árpád ; Dima, Delia ; Kim, Dong-Wook ; Badar, Talha ; Inamdar, Sandeep ; García-Gutiérrez, Valentin ; Rathnam, Krishnakumar ; Abruzzese, Elisabetta ; Nag, Arijit ; Lucchesi, Alessandro ; Alvarado, Yesid ; Khattry, Navin ; Saikia, Tapan ; Saxena, Unnati ; Cortes, Jorge E ; Nicolini, Franck E ; Apperley, Jane F ; Sreenivasan, Jayasree

BACKGROUNDResistance or intolerance to the available tyrosine kinase inhibitors (TKIs) remains a treatment challenge for patients with chronic myeloid leukaemia. We aimed to report the safety, antileukaemic activity, and pharmacokinetics of oral vodobatinib, a novel selective BCR::ABL1 TKI, in patients with Philadelphia chromosome-positive (Ph-positive) chronic myeloid leukaemia who previously received at least three TKIs, including ponatinib and asciminib.METHODSThis open-label, multicentre, phase 1/2 trial was conducted at 28 clinical sites across ten countries (Belgium, France, Hungary, India, Italy, Romania, South Korea, Spain, UK, and the USA). Patients aged 18 years or older with Ph-positive chronic myeloid leukaemia or acute lymphoblastic leukaemia (eligible only for the phase 1 study), and an Eastern Cooperative Oncology Group performance status of 2 or lower were eligible. Phase 1 included patients who previously received at least three TKIs or had no other available treatment options. Phase 2 required patients to have treatment resistance or intolerance (or both) with loss of response to at least three TKIs and previous ponatinib use. A key exclusion criterion for both phases was presence of the Thr315Ile mutation. Patients self-administered oral vodobatinib (12-240 mg) once per day for each 28-day treatment cycle and for up to 60 months (ie, 65 cycles) unless patient discontinuation due to adverse events, progressive disease, lost to follow-up, or death. The primary endpoints were to determine the maximum tolerated dose (based on dose-limiting toxicities in phase 1) and antileukaemic activity of vodobatinib (ie, major cytogenetic response for chronic-phase and major haematological response for accelerated-phase or blast-phase in phase 2). Assessment of vodobatinib safety, activity, and pharmacokinetics were determined based on the pooled analysis of data from the phase 1 and 2 studies. This trial is registered with ClinicalTrials.gov, NCT02629692 (active). At data cutoff (July 15, 2023), phase 2 enrolment was closed early on June 22, 2023, due to recruitment-related challenges.FINDINGS78 patients were enrolled and received at least one vodobatinib dose (safety and efficacy analysis set). Between April 6, 2017, and June 20, 2023, phase 1 enrolled 58 patients and phase 2 enrolled 20 patients between March 3, 2020, and March 29, 2023. We included 66 (85%) patients with chronic-phase, eight (10%) with accelerated-phase, and four (5%) with blast-phase chronic myeloid leukaemia. 43 (55%) of 78 patients were male and 35 (45%) were female. The median age was 59·0 years (IQR 47·0-66·0). The median follow-up was 22·3 months (IQR 11·1-43·9). Two patients receiving vodobatinib 240 mg had dose-limiting toxicities (one had grade 3 dyspnoea and the other had grade 2 fluid overload), thus the 204 mg dose was considered to be the maximum tolerated dose. 73 (94%) patients had one or more treatment-emergent adverse events, with most events being haematological or gastrointestinal that were grade 2 or lower in severity. Grade 3 or higher treatment-emergent adverse events occurred in 47 (60%) patients and included thrombocytopenia (14 [18%]), neutropenia (10 [13%]), anaemia (nine [12%]), and increased lipase (eight [10%]). Seven (9%) patients died during the study; one death was considered related to treatment by the clinical investigator. At data cutoff, major cytogenetic response was observed in 44 (70%) of 63 patients with chronic-phase chronic myeloid leukaemia, of which 12 (75%) of 16 patients in the phase 2 study had major cytogenetic response. For patients with accelerated-phase chronic myeloid leukaemia, six (86%) of seven patients had a major haematological response (median duration 17·8 [IQR 10·2-24·3]) at data cutoff; major haematological response was observed in three (100%) evaluable patients in the phase 2 study. Major haematological response was reached by two (50%) of four patients with blast-phase chronic myeloid leukaemia and the median duration of response was 6·2 months (IQR 3·2-9·3); no blast-phase patients were enrolled in the phase 2 study.INTERPRETATIONPooled analysis of the phase 1 and 2 studies showed clinically meaningful antileukaemic activity of vodobatinib and a tolerable safety profile in patients with advanced chronic myeloid leukaemia who previously received multiple TKIs, including ponatinib and asciminib, addressing an otherwise unmet clinical need. The phase 2 study was statistically underpowered and warrants further investigation in a phase 3, randomised controlled trial and in an earlier treatment setting of the disease.FUNDINGSun Pharma Advanced Research Company.

01 Feb 2025·European Journal of Pharmacology

Vodobatinib overcomes cancer multidrug resistance by attenuating the drug efflux function of ABCB1 and ABCG2

Article

Author: Wu, Yu-Shan ; Hung, Tai-Ho ; Murakami, Megumi ; Chen, Chin-Chuan ; Wu, Chung-Pu ; Li, Yen-Ching ; Lin, Bing-Huan ; Ambudkar, Suresh V

Multidrug resistance (MDR) remains a significant obstacle in cancer treatment, primarily attributable to the overexpression of ATP-binding cassette (ABC) transporters such as ABCB1 and ABCG2 within cancer cells. These transporters actively diminish the effectiveness of cytotoxic drugs by facilitating ATP hydrolysis-dependent drug efflux, thereby reducing intracellular drug accumulation. Given the absence of approved treatments for multidrug-resistant cancers and the established benefits of combining tyrosine kinase inhibitors (TKIs) with conventional anticancer drugs, we investigate the potential of vodobatinib, a potent c-Abl TKI presently in clinical trials, to restore sensitivity to chemotherapeutic agents in multidrug-resistant cancer cells overexpressing ABCB1 and ABCG2. Results indicate that vodobatinib, administered at sub-toxic concentrations, effectively restores the sensitivity of multidrug-resistant cancer cells to cytotoxic drugs in a concentration-dependent manner. Moreover, vodobatinib enhances drug-induced apoptosis in these cells by inhibiting the drug-efflux function of ABCB1 and ABCG2, while maintaining their expression levels. Moreover, we found that while vodobatinib enhances the ATPase activity of ABCB1 and ABCG2, the overexpression of these transporters does not induce resistance to vodobatinib. These results strongly suggest that increased levels of ABCB1 or ABCG2 are unlikely to play a significant role in the development of resistance to vodobatinib in cancer patients. Overall, our findings unveil an additional pharmacological facet of vodobatinib against ABCB1 and ABCG2 activity, suggesting its potential incorporation into combination therapy for a specific subset of patients with tumors characterized by high ABCB1 or ABCG2 levels. Further investigation is warranted to fully elucidate the clinical implications of this therapeutic approach.

01 Feb 2025·Biomedical Chromatography

Validated HPLC‐UV Method for the Quantification of a Novel BCr‐Abl 1 Inhibitor, Vodobatinib, in Rat Plasma: Application to a Pharmacokinetic Study

Article

Author: Bestha, Rama Murthi ; Dittakavi, Sreekanth ; Kumar, Rajnish ; Veerla, Niranjan ; Madipelli, Keerthana ; Mullangi, Ramesh ; Kaddare, Sandeep ; Biradar, Yogesh Balaji ; Zakkula, Ashok

ABSTRACTVodobatinib is a Bcr‐Abl 1 inhibitor, currently entering into Phase 2 clinical trials as a potential drug to treat glioblastoma patients. In the present work, a validated high‐performance liquid chromatography (HPLC) detection method for the quantification of vodobatinib in rat plasma was established. Sample preparation involved liquid–liquid extraction method. The chromatographic separation of vodobatinib and the IS was accomplished on an XBridge C18 column using 10 mM ammonium acetate and acetonitrile in gradient condition. The flow‐rate and injection volume were 0.8 mL/min and 20 μL, respectively. The eluent was detected at 310 nm. Vodobatinib and the IS eluted at 7.5 and 5.9 min, respectively, with a total run time of 10 min. Validation tests were performed according to FDA requirements. The established method showed good linearity in the range of 50.5–6534 ng/mL. Interday and intraday coefficients of variations were < 5.11%. Stability studies, dilution integrity, and incurred sample reanalysis met the acceptance criteria. Subsequently, the validated HPLC method was used to study the disposition kinetics of vodobatinib in rats.

100 Deals associated with Vodobatinib

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Philadelphia positive acute lymphocytic leukaemia	Phase 2	India	Sun Pharma Advanced Research Co. Ltd.	27 Jun 2016
Philadelphia positive acute lymphocytic leukaemia	Phase 2	United Kingdom	Sun Pharma Advanced Research Co. Ltd.	27 Jun 2016
Philadelphia positive acute lymphocytic leukaemia	Phase 2	South Korea	Sun Pharma Advanced Research Co. Ltd.	27 Jun 2016
Philadelphia positive acute lymphocytic leukaemia	Phase 2	Hungary	Sun Pharma Advanced Research Co. Ltd.	27 Jun 2016
Philadelphia positive acute lymphocytic leukaemia	Phase 2	France	Sun Pharma Advanced Research Co. Ltd.	27 Jun 2016
Philadelphia positive acute lymphocytic leukaemia	Phase 2	Turkey	Sun Pharma Advanced Research Co. Ltd.	27 Jun 2016
Philadelphia positive acute lymphocytic leukaemia	Phase 2	Italy	Sun Pharma Advanced Research Co. Ltd.	27 Jun 2016
Philadelphia positive acute lymphocytic leukaemia	Phase 2	Belgium	Sun Pharma Advanced Research Co. Ltd.	27 Jun 2016
Philadelphia positive acute lymphocytic leukaemia	Phase 2	United States	Sun Pharma Advanced Research Co. Ltd.	27 Jun 2016
refractory chronic myelocytic leukemia	Phase 2	United States	Sun Pharma Advanced Research 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


NCT02629692 (ASH 12021 \| ASH 22021) Manual	Phase 1	Philadelphia positive acute lymphocytic leukaemia \| Philadelphia chromosome positive chronic myelogenous leukemia Last line Philadelphia Chromosome Positive	52	vodobatinib (dose-escalation (DEs))	(coihztixxi) = Nineteen pts (37%) reported SAEs; vodobatinib related SAEs were reported in 3 pts (fatal intracranial haemorrhage (ICH), Grade 2 back pain and Grade 3 amnesia reported in 1 pt each) htslgjtlcr (lcvbyqptoq ) View more	Positive	05 Nov 2021
				vodobatinib 174 mg (dose-expansion (DEx))