Delving into the Latest Updates on Mesna with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Mesna (JAN/USP/INN), Mesonex, 美司那

+ [9]

Target-

Mechanism-

Therapeutic Areas

Urogenital DiseasesOther Diseases

Active Indication

DysuriaHemorrhagic cystitis

Inactive Indication-

Originator Organization

Baxter International, Inc.

Active Organization

Shionogi & Co., Ltd.Baxter Healthcare Corp.

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

US (30 Dec 1988),

Hemorrhagic cystitis

RegulationOrphan Drug (JP)

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Structure

Molecular FormulaC2H6NaO3S2

InChIKeyPYTISYCTLQTCTM-UHFFFAOYSA-N

CAS Registry19767-45-4

The study participant has one of the following blood cancers: acute myelogenous leukemia (AML)/myelodysplastic syndrome (MDS), acute lymphoblastic leukemia (B-ALL, T-ALL) or Lymphoma. Your cancer has been difficult to treat (refractory) or has come back after treatment (relapse).
Primary Objective
To determine the safety and maximum tolerated dose of intravenous infusions of escalating doses of CD70-CAR T cells in patients (≤21 years) with recurrent/refractory CD70+ hematological malignancies after lymphodepleting chemotherapy.
Secondary Objectives
To evaluate the antileukemic activity of CD70-CAR T cells. We will determine the anti- leukemic activity of the CD70-CAR T cells in the bone marrow and in the treatment of extramedullary disease.

Start Date01 Dec 2024

Sponsor / Collaborator

St. Jude Children's Research Hospital, Inc.

NCT06677710 / Not yet recruitingPhase 1

A Phase 1B Study of IDP-023 g-NK Cells Plus Ocrelizumab in Patients With Refractory Primary and Secondary Progressive Multiple Sclerosis

This is an open label, Phase 1b, multiple ascending dose, and dose-expansion study of IDP-023 administered in combination with interleukin-2 (IL-2) and ocrelizumab to evaluate the safety, tolerability, and biologic activity on autoreactive immune cells in patients with refractory progressive multiple sclerosis.

Start Date01 Nov 2024

Sponsor / Collaborator

Indapta Therapeutics, Inc.Startup

100 Clinical Results associated with Mesna

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100 Translational Medicine associated with Mesna

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100 Patents (Medical) associated with Mesna

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1,268

Literatures (Medical) associated with Mesna

01 Nov 2024·Redox Biology

Mechanism of action and impact of thiol homeostasis on efficacy of an enzyme replacement therapy for classical homocystinuria

Article

Author: Bottiglieri, Teodoro ; Philipp, Thilo Magnus ; Szabo, Csaba ; Clapper, Wilmelenne ; Liu, Kai ; Rodems, Steve ; Majtan, Tomas

Homocystinuria (HCU) due to cystathionine beta-synthase (CBS) deficiency is characterized by elevated plasma and tissue homocysteine levels. There is no cure, but HCU is typically managed by methionine/protein restriction and vitamin B₆ supplementation. Enzyme replacement therapy (ERT) based on human CBS has been developed and has shown significant efficacy correcting HCU phenotype in several mouse models by bringing plasma total homocysteine below the clinically relevant 100 μM threshold. As the reactive nature of homocysteine promotes disulfide formation and protein binding, and ERT is unable to normalize plasma total homocysteine levels, the mechanism of action of ERT in HCU remains to be further characterized. Here we showed that only a reduced homocysteine serves as a substrate for CBS and its availability restricts the homocysteine-degrading capacity of CBS. We also demonstrated that cells export homocysteine in its reduced form, which is efficiently metabolized by CBS in the culture medium. Availability of serine, a CBS co-substrate, was not a limiting factor in our cell-based model. Biological reductants, such as N-acetylcysteine, MESNA or cysteamine, increased the availability of the reduced homocysteine and thus promoted its subsequent CBS-based elimination. In a transgenic I278T mouse model of HCU, administration of biological reductants significantly increased the proportion of protein-unbound homocysteine in plasma, which improved the efficacy of the co-administered CBS-based ERT, as evidenced by significantly lower plasma total homocysteine levels. These results clarify the mechanism of action of CBS-based ERT and unveil novel pharmacological approaches to further increase its efficacy.

01 Sep 2024·Cancer Medicine

Camrelizumab in combination with doxorubicin, cisplatin, ifosfamide, and methotrexate in neoadjuvant treatment of resectable osteosarcoma: A prospective, single‐arm, exploratory phase II trial

Article

Author: Tang, Qinglian ; Xu, Huaiyuan ; Wu, Hao ; Deng, Chuangzhong ; Ai, Fei ; Lu, Jinchang ; Zhang, Yingchun ; Zhang, Xinke ; Song, Guohui ; Zhu, Xiaojun ; Wang, Jin

AbstractBackgroundThe poor overall survival of osteosarcoma (OS) underscores the need to explore new therapeutic avenues. Tumor necrosis rate (TNR) after neoadjuvant chemotherapy predicts prognosis.AimsThe study was to investigate safety and activity of neoadjuvant chemotherapy with camrelizumab (a humanized antibody against PD‐1) in patients with resectable OS.Materials & MethodsWe conducted a prospective, single‐arm, exploratory phase II trial in OS patients. Eligible patients received camrelizumab combined with doxorubicin or liposomal doxorubicin, cisplatin, methotrexate, ifosfamide with mesna. Surgery was performed 12–14 days after neoadjuvant therapy and adjuvant therapy starting 2–3 weeks postoperatively. The primary endpoint was the rate of good tumor necrosis (TNR ≥90%) after neoadjuvant therapy, and the secondary outcomes were safety, 2‐year progression free survival and 2‐year overall survival.ResultsSeventy‐five patients were recruited to the study. Subsequently, 64 patients completed neoadjuvant therapy and underwent surgery. Thirty‐one patients (48.4%) have a good TNR to neoadjuvant therapy. With a median follow‐up of 22.4 months (range 2.2–44.9 months), the estimated 2‐year PFS was 69.6% and the estimated 2‐year overall survival was 89.4%. Grade 3 or 4 treatment‐related adverse events were noticed in 62.7% of the patients. Frequent grade 3 or 4 adverse events were decreased platelet count (45.3%), decreased white blood cell count (36%). No immune‐related serious adverse events were observed.DiscussionOur study had limitations. First, it was limited by its non‐randomized design. Besides, stromal tumor‐infiltrating lymphocytes was comprehensively analyzed in this study.ConclusionsThis study demonstrated that amrelizumab combined with adriamycin, cisplatin, methotrexate, and ifosfamide in the neoadjuvant treatment of resectable OS was safe and tolerable. This combined therapeutic strategy may not increase TNR, but the long‐term survival benefit remains to be followed up.

01 Jul 2024·eClinicalMedicine

Pegylated liposomal doxorubicin combined with cyclophosphamide and vincristine in pediatric patients with relapsed/refractory solid tumor: a single-arm, open-label, phase I study

Article

Author: Huang, Junting ; Guo, Ying ; Lu, Suying ; Cai, Ruiqing ; Zhen, Zijun ; Que, Yi ; Sun, Xiaofei ; Zhang, Yizhuo ; Sun, Feifei ; Wang, Juan ; Li, Hui ; Zhu, Jia

BackgroundThe combined vincristine, pegylated liposomal doxorubicin (PLD), and cyclophosphamide (VPC) regimen has never been studied in pediatric patients.MethodsThis open-label, single-center, single-arm phase I study utilizing a "3 + 3" design enrolled children with relapsed/refractory (R/R) solid tumors. Three dose levels of PLD (Duomeisu®) were studied (30, 40, or 50 mg/m²) in combination with cyclophosphamide (1500 mg/m²), mesna (1500 mg/m²), and vincristine (1.5 mg/m², maximum 2 mg) once every 3 weeks. The primary endpoints included safety, the maximum tolerated dose (MTD) of PLD (Duomeisu®), and the recommended phase 2 dose (RP2D) of PLD (Duomeisu®) for further phase 2 investigation. The secondary endpoints were objective response rate (ORR) and disease control rate (DCR). This study is registered with ClinicalTrials.gov, NCT04213612.FindingsBetween January 7, 2020, and November 18, 2021, 34 patients were eligible and evaluable for toxicity, while 26 patients were evaluable for response. The MTD of PLD (Duomeisu®) was 30 mg/m². The most common adverse event (AE) was grade 3 or 4 neutropenia (61.8%). The most common grade 1 or 2 non-hematologic AE and cardiotoxicity effects were vomiting (35.3%) and abnormal electrocardiogram T waves (20.6%), respectively. ORR and DCR to VPC regimen after two cycles were 50.0% and 92.3%, respectively. Targeted gene panel sequencing revealed the activation of TP53 mutation may be an adverse prognostic factor.InterpretationThe VPC regimen showed a promising safety profile and had preliminary efficacy in children with R/R solid tumors. The RP2D for PLD (Duomeisu®) combined with cyclophosphamide and vincristine is 30 mg/m² once every 3 weeks.FundingCSPC Ouyi Pharmaceutical Co., Ltd., Shijiazhuang, the National Key Research and Development Program of China [No. 2022YFC2705005], the National Natural Science Foundation of China [No. 82203303], and the Basic and Applied Basic Research Foundation of Guangdong Province [No. 2021A1515110234].

100 Deals associated with Mesna

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External Link

KEGG	Wiki	ATC	Drug Bank
D01459	Mesna	R05CB05 V03AF01	DB09110

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Dysuria	JP	Shionogi & Co., Ltd.	05 Oct 1994
Dysuria	JP	Baxter Healthcare Corp.	05 Oct 1994
Hemorrhagic cystitis	US	Baxter Healthcare Corp.	30 Dec 1988

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00936936 (CTgov)	Phase 2	Testicular Neoplasms \| Germ Cell and Embryonal Neoplasms	64	Bevacizumab (Cohort 1: HD GeM-DMC+ ICE + Bevacizumab for Refractory GCT)	(rawlefvvzd) = lcjbhkilvr xqytokqjtd (zxrqevhtnf, blgpwekzna - uzcsqeyrrb) View more	-	26 Aug 2024
NCT00936936 (CTgov)	Phase 2	Testicular Neoplasms \| Germ Cell and Embryonal Neoplasms	64	Mesna+Etoposide+Carboplatin+Melphalan+Ifosfamide+Gemcitabine+Docetaxel (Cohort 2: HD GeM-DMC+ ICE for Refractory GCT)	(rawlefvvzd) = ypznjmnkuz xqytokqjtd (zxrqevhtnf, ncshplpkiv - vzrtarqxnr) View more	-	26 Aug 2024
NCT03056339 (CTgov)	Phase 1/2	Chronic Lymphocytic Leukemia \| Acute Lymphoblastic Leukemia \| B-Cell Lymphoma \| Non-Hodgkin Lymphoma	49	steroids+Mesna+Fludarabine+cyclophosphamide+AP1903+iC9/CAR.19/IL15-transduced CB-NK cells (Group 1: 1x105 NK Cells /kg)	lgsutfrdkw(vpsxjdjdej) = yejdhhmwzf ftabbtbvru (clwlvxoyfv, vglscmnhso - psjjcnkkix) View more	-	25 Mar 2024
NCT03056339 (CTgov)	Phase 1/2		49	steroids+Mesna+Fludarabine+cyclophosphamide+AP1903+iC9/CAR.19/IL15-transduced CB-NK cells (Group 2: 1x106 NK Cells /kg)	lgsutfrdkw(vpsxjdjdej) = whwtxvkuwz ftabbtbvru (clwlvxoyfv, gvdoxxnhbj - ohnehvrkft) View more	-	25 Mar 2024
NCT04959175 (Tandem Meetings ASTCT and CIBMTR2024) Manual	Phase 1/2	Hematologic Neoplasms	40	Mycophenolate Mofetil+Allogeneic HSCT+Fludarabine+Sirolimus+Filgrastim+Cyclophosphamide+Mesna+Total Body Irradiation (TBI)	(ddytamoavp) = edavvicwlh zhuhnvkwrf (hlyviurevp ) View more	Positive	01 Feb 2024
NCT01850108 (CTgov)	Not Applicable	Anemia, Sickle Cell	26	Bone marrow transplantation+Mesna+Fludarabine+Thymoglobulin+Sirolimus+Mycophenolate mofetil (MMF)+Cyclophosphamide (CTX)	(jolfbalbqg) = ixkstyoogf jznllhgpar (lkwhbbwqrb, przlioaffa - jqctqomxli) View more	-	10 Jan 2024
NCT02224872 (CTgov)	Phase 2	Anemia, Aplastic \| Refractory Severe Aplastic Anemia	18	Bone marrow transplant+Mesna+Fludarabine+Cyclophosphamide+Thymoglobulin+Tacrolimus+Mycophenolic acid mofetil	fqfipnfzyp(cpbxfwfcab) = flgbokbsqq sispdthkxa (okjclkvymi, ztfgbidwae - hwziazhplu) View more	-	10 Mar 2023
NCT04318678 (CATCHAML, ASH2022) Manual	Phase 1	Acute Myeloid Leukemia	-	Rituximab+Mesna+Fludarabine Phosphate+Cyclophosphamide+CD123-CAR T Cells(St. Jude Children's Research Hospital)	(lphyojykdh) = sewjvrjxdn dwjwxfyknh (gjnzpggifu ) View more	Positive	15 Nov 2022
NCT01319981 (CTgov)	Phase 2	Acute Lymphoblastic Leukemia	31	Pegfilgrastim+Mesna+CYCLOPHOSPHAMIDE+G-CSF+Doxorubicin+Imatinib+VSLI+Dexamethasone+Rituximab (Hyper-CMAD + Rituximab)	mdyxxozwie(uymqdfsinz) = oplmuitbbc beddbhqiwp (yqvmlvcajh, iylkuelsgz - vxxugkuala) View more	-	27 Sep 2022
NCT01319981 (CTgov)	Phase 2	Acute Lymphoblastic Leukemia	31	Pegfilgrastim+Solu-Medrol+G-CSF+Imatinib+VSLI+Rituximab+Methotrexate+Ara-C (Hyper-CMAD)	mdyxxozwie(uymqdfsinz) = mzcflbvbbt beddbhqiwp (yqvmlvcajh, qvvrjhmvxw - eexhvwxrkc) View more	-	27 Sep 2022
NCT00177047 (CTgov)	Phase 2/3	Multiple Myeloma	363	Granulocyte-colony stimulating factor+Mesna+Cyclophosphamide+melphalan	piuysyiyuh(qsiwqwlsae) = fjyopkumei pmjbuouwfs (rhmsgldkhg, gannlahhgz - nnnjoseqxw) View more	-	09 Nov 2021
NCT03342638 (MOST, CTgov)	Phase 3	Multiple Sclerosis, Relapsing-Remitting	66	Autologous Stem Cells+Mesna+Methylprednisolone+Cyclophosphamide+rATG+G-CSF (Control Arm)	fmqphsffbd(memdicztyp) = flryzrjpfa hvwszwamor (ygzlkylfss, mkusubnbqj - xnvwzhtoaq) View more	-	11 Jan 2021
NCT03342638 (MOST, CTgov)	Phase 3	Multiple Sclerosis, Relapsing-Remitting	66	Autologous Stem Cells+Mesna+Methylprednisolone+Cyclophosphamide+rATG+G-CSF (IVIg Arm)	fmqphsffbd(memdicztyp) = uxftmpdass hvwszwamor (ygzlkylfss, zayrowegjf - shfqvgoivn) View more	-	11 Jan 2021
NCT02282514 (SPS, CTgov)	Phase 1/2	Progressive Encephalomyelitis With Rigidity \| Stiff-Person Syndrome	23	Autologous Hematopoietic Stem Cells+Mesna+Methylprednisolone+CYCLOPHOSPHAMIDE+rATG+G-CSF+Rituxan	(zrcreyfjqs) = vgrqgdazyq quxlxhucpw (iugptqeezl, gkqbwbxpdk - nvsfzaexap) View more	-	06 Jan 2021