Delving into the Latest Updates on Marizomib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

MRZ, Marizomib (USAN/INN), Salinosporamide A

+ [2]

Target

Proteasome

Action

inhibitors, stimulants

Mechanism

Proteasome inhibitors, Apoptosis stimulants

Therapeutic Areas

NeoplasmsNervous System DiseasesOther Diseases

Active Indication

Recurrent GlioblastomaGlioblastoma

Inactive Indication

Advanced cancerAdvanced Malignant Solid NeoplasmDiffuse Intrinsic Pontine Glioma+ [9]

Originator Organization

Triphase Accelerator Corp.

Active Organization

Celgene Corp.

Triphase Accelerator Corp.

Inactive Organization

Bristol Myers Squibb Co.

Drug Highest PhasePhase 3

First Approval Date-

RegulationOrphan Drug (European Union)

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Structure/Sequence

Molecular FormulaC15H20ClNO4

InChIKeyNGWSFRIPKNWYAO-SHTIJGAHSA-N

CAS Registry437742-34-2

Background:
Ependymomas are rare tumors that arise from the ependyma. That is a tissue of the central nervous system. They can develop in the brain or the spine. They are usually treated with surgery, radiation, and/or chemotherapy. Researchers want to see if the new drug marizomib can help people with a certain kind of ependymoma.
Objective:
To see if marizomib stops tumor growth and prolongs the time that the tumor is controlled.
Eligibility:
Adults age 18 and older who have been diagnosed with ependymomas and have already been treated with standard therapies
Design:
Participants will be screened with the following tests or recent results from similar tests:
Medical history
Physical exam
Neurological assessment
Electrocardiogram (EKG) to evaluate the heart
Review of symptoms and ability to perform normal activities
Computed tomographic scan (CT) or magnetic resonance imaging (MRI) to produce an image of the brain or spine.
Blood and urine tests
Tests of tumor samples. Participants may have to have new tumor samples taken.
Participants will get the study drug in cycles. Each cycle is 4 weeks. Participants will have up to 24 cycles.
Participants will get the study drug through a small plastic tube in a vein on days 1, 8, and 15 of each cycle.
During each cycle, some screening tests will be repeated.
Participants will answer questions about their general well-being and functioning.
About 4 5 weeks after finishing the study drug, participants will have a follow-up visit. They will answer questions about their health, get a physical and a neurological exam, and have blood tests. They may have an MRI or CT scan.
...

Start Date22 Jan 2020

Sponsor / Collaborator

National Cancer Institute

100 Clinical Results associated with Marizomib

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100 Translational Medicine associated with Marizomib

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100 Patents (Medical) associated with Marizomib

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415

Literatures (Medical) associated with Marizomib

01 Jan 2025·Journal of the Neurological Sciences

MRZ-reaction maybe influenced by immunization status and is not exclusive to multiple sclerosis

Article

Author: Sudhir, Akshatha ; D'Cunha, Mary Anitha ; Pandit, Lekha

BACKGROUNDAmong white populations, a poly-specific antibody response against measles (M), rubella (R) and varicella zoster(Z) otherwise known as MRZR is seen in ∼70 % of MS and rarely in other demyelinating disorders. While the basis for MRZR is unclear, vaccination exposure / community acquired infections may have an influence on its frequency.OBJECTIVETo determine the frequency and specificity of MRZR in MS and related disorders in a non- white population with historically low vaccinations and to contrast against oligoclonal bands (OCB).METHODSIn all, 167 consecutive patients (MS -96, MOGAD-33, AQP4-IgG + NMOSD-12 & double seronegative disorders[DSD] -26) were included. Clinical diagnosis, vaccination history and past infections contributing to MRZR were queried, OCB results were reviewed and MRZR measured.RESULTMRZR+ response was seen in 50 % MS, 21.2 % MOGAD, 8.3 %NMOSD and 3.8 % of DSN disease. Vaccination history was limited, a past history of Z was notably associated (p 0.005) with MRZR-Z+ and a high median antibody index was detected for Z and R (p 0.001) in MS. Among MRZR+ patients with MOGAD, a disseminated disease that included LETM (p 0.007), relapsing course (p 0.02), higher relapse rate (p 0.001) and lumbar puncture performed after 2 or more attacks(p 0.009) were significant. CSF specific OCB was more sensitive (71.9 %;95 %CI 61.8-80.6) and specific (94.4 %;95 %CI 86.2-98.4) than MRZR (sensitivity 50 % [95 %CI 39.62-60.4] and specificity 87.3 %(95 %CI 77.3-94.04) for MS patients.CONCLUSIONIn this south Indian cohort with historically low vaccination status, community acquired immunity may have in part influenced MRZR+ results, especially MRZR-Z. A chronic inflammatory state is a likely pre-requisite, that may not be disease specific, for MRZR positivity in immunologically overlapping CNS disorders such as MS, MOGAD and others.

12 Nov 2024·ACS Omega

Evaluating Antimalarial Proteasome Inhibitors for Efficacy in Babesia Blood Stage Cultures

Article

Author: Jalovecká, Marie ; Šnebergerová, Pavla ; Robbertse, Luïse ; Almaliti, Jehad ; O’Donoghue, Anthony J. ; Fajtová, Pavla ; Barbosa da Silva, Elany ; Gerwick, William H. ; Bouřa, Evžen ; Pachl, Petr ; Al-Hindy, Momen ; Levytska, Viktoriya ; Sojka, Daniel ; Sharma, Vandna

Tick-transmitted Babesia are a major global veterinary threat and an emerging risk to humans. Unlike their Plasmodium relatives, these erythrocyte-infecting Apicomplexa have been largely overlooked and lack specific treatment. Selective targeting of the Babesia proteasome holds promise for drug development. In this study, we screened a library of peptide epoxyketone inhibitors derived from the marine natural product carmaphycin B for their activity against Babesia. Several of these compounds showed activity against both the asexual and sexual blood stages of Plasmodium falciparum. These compounds inactivate β5 proteasome subunit activity in the lysates of Babesia divergens and Babesia microti in the low nanomolar range. Several compounds were tested with the purified B. divergens proteasome and showed IC₅₀ values comparable to carfilzomib, an approved anticancer proteasome inhibitor. They also inhibited B. divergens growth in bovine erythrocyte cultures with solid EC₅₀ values, but importantly, they appeared less toxic to human cells than carfilzomib. These compounds therefore offer a wider therapeutic window and provide new insights into the development of small proteasome inhibitors as selective drugs for babesiosis.

05 Sep 2024·Neuro-Oncology

Marizomib for patients with newly diagnosed glioblastoma: A randomized phase 3 trial

Article

Author: Idbaih, Ahmed ; van den Bent, Martin ; Lukacova, Slavka ; Roth, Patrick ; Blais, Andre ; Freres, Pierre ; Sepulveda, Juan Manuel ; Balana, Carmen ; Nicholas, Garth ; O’Callaghan, Chris J ; Weller, Michael ; Seidel, Clemens ; Gorlia, Thierry ; Frenel, Jean-Sébastien ; Nuyens, Sarah ; Vanlancker, Maureen ; Perry, James ; Mason, Warren ; Ducray, Francois ; Preusser, Matthias ; Masucci, G Laura ; Meijnders, Paul ; Dhermain, Fréderic ; Le Rhun, Emilie ; Hirte, Hal ; Verschaeve, Vincent ; de Vos, Filip ; Reijneveld, Jaap C ; Bota, Daniela A ; Walenkamp, Annemiek

AbstractBackgroundStandard treatment for patients with newly diagnosed glioblastoma includes surgery, radiotherapy (RT), and temozolomide (TMZ) chemotherapy (TMZ/RT→TMZ). The proteasome has long been considered a promising therapeutic target because of its role as a central biological hub in tumor cells. Marizomib is a novel pan-proteasome inhibitor that crosses the blood–brain barrier.MethodsEuropean Organisation for Research and Treatment of Cancer 1709/Canadian Cancer Trials Group CE.8 was a multicenter, randomized, controlled, open-label phase 3 superiority trial. Key eligibility criteria included newly diagnosed glioblastoma, age > 18 years and Karnofsky performance status > 70. Patients were randomized in a 1:1 ratio. The primary objective was to compare overall survival (OS) in patients receiving marizomib in addition to TMZ/RT→TMZ with patients receiving the only standard treatment in the whole population and in the subgroup of patients with MGMT promoter-unmethylated tumors.ResultsThe trial was opened at 82 institutions in Europe, Canada, and the U.S. A total of 749 patients (99.9% of the planned 750) were randomized. OS was not different between the standard and the marizomib arm (median 17 vs. 16.5 months; HR = 1.04; P = .64). PFS was not statistically different either (median 6.0 vs. 6.3 months; HR = 0.97; P = .67). In patients with MGMT promoter-unmethylated tumors, OS was also not different between standard therapy and marizomib (median 14.5 vs. 15.1 months, HR = 1.13; P = .27). More CTCAE grade 3/4 treatment-emergent adverse events were observed in the marizomib arm than in the standard arm.ConclusionsAdding marizomib to standard temozolomide-based radiochemotherapy resulted in more toxicity, but did not improve OS or PFS in patients with newly diagnosed glioblastoma.

100 Deals associated with Marizomib

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External Link

KEGG	Wiki	ATC	Drug Bank
D09640	Marizomib	-	DB11762

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Recurrent Glioblastoma	Phase 3	Germany	Celgene Corp.	26 Jul 2018
Recurrent Glioblastoma	Phase 3	Spain	Celgene Corp.	26 Jul 2018
Recurrent Glioblastoma	Phase 3	United Kingdom	Celgene Corp.	26 Jul 2018
Recurrent Glioblastoma	Phase 3	Netherlands	Celgene Corp.	26 Jul 2018
Recurrent Glioblastoma	Phase 3	Canada	Celgene Corp.	26 Jul 2018
Recurrent Glioblastoma	Phase 3	Denmark	Celgene Corp.	26 Jul 2018
Recurrent Glioblastoma	Phase 3	France	Celgene Corp.	26 Jul 2018
Recurrent Glioblastoma	Phase 3	United States	Celgene Corp.	26 Jul 2018
Recurrent Glioblastoma	Phase 3	Norway	Celgene Corp.	26 Jul 2018
Glioblastoma	Phase 3	-	Triphase Accelerator Corp.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03345095 (EORTC 1709/CCTG CE.8 \| MIRAGE, CTgov)	Phase 3	Glioblastoma \| Recurrent Glioblastoma	749	radiotherapy+Temozolomide+Marizomib (Experimental Arm)	(wnosvgqout) = whlahztxyr ooevujjimp (cpfrehmhnc, ogzgumyndl - zpoqoygwbp) View more	-	31 Jan 2024
				radiotherapy+Temozolomide (Standard Arm)	(wnosvgqout) = hqcrzpwmbb ooevujjimp (cpfrehmhnc, mnvngrzabh - zgsywsnszl) View more
P11.84.A (EANO2023)	Phase 1	Diffuse Intrinsic Pontine Glioma	4	Marizomib alone	lhdjhqqkgf(kdmvsaguuk) = Adverse events were related to disease/tumor progression or considered mild (grade 1 headache, emesis, diarrhea, fatigue, lymphopenia, thrombocytopenia) with the exception of sinus tachycardia and dyspnea (grade 2) (n=1) wjrqoqrqva (ztwjtcnlzj )	Positive	08 Sep 2023
				Marizomib + Panobinostat
NCT03345095 (EORTC 1709/CCTG CE.8, ASCO2021)	Phase 3	Glioblastoma	749	Marizomib + TMZ/RT → TMZ	(hacrknuput) = fylzktaajb inngaincoo (wrdsbaiwrn ) View more	Negative	28 May 2021
				TMZ/RT → TMZ	(hacrknuput) = duiiflspct inngaincoo (wrdsbaiwrn ) View more
NCT02903069 (ASCO 12019 \| ASCO 22019) Manual	Phase 1	Glioblastoma First line	66	temozolomide+radiotherapy+marizomib	chnozdgmfc(oqmavhetth) = nqqzkgswpd mczhihwbfo (ezbsxifxat ) View more	Positive	02 Jun 2019
NCT02103335 (NPI-0052-107, Pubmed) Manual	Phase 1	Multiple Myeloma	38	pomalidomide+dexamethasone+marizomib	(cjdugwtbdd) = cyvlyaclmk tdjoohjmua (byxinawvoe ) View more	Positive	01 Jan 2018
NCT00461045 (NPI-0052-101, CTgov)	Phase 2	Multiple Myeloma	15	MRZ 0.5 mg/m^2	sjdgisedwz(hmrebkgdoz) = tpzwybirwj cwpzvxevve (xrxhfdmues, kjgptjtbof - rlbprhjvgh) View more	-	13 Sep 2017
NCT00629473 (NPI-0052-102, Pubmed \| Clin Cancer Res) Manual	Phase 1	Multiple Myeloma \| Neoplasms	86	Marizomib (patients with relapsed and/or refractory multiple myeloma (RRMM) and other hematologic malignancies)	(dxytehqdzl) = The Schedule A recommended phase II dose was 0.7 mg/m(2) over 10 minutes; Schedule B was 0.5 mg/m(2) over 2 hours. khqltagtha (ossxxkvekk ) View more	Positive	15 Sep 2016
				Marizomib
NCT00461045 (NPI-0052-101, Pubmed \| Circulation \| Blood) Manual	Phase 1	Refractory Multiple Myeloma	68	dexamethasone+marizomib	(llurfmclxh) = zmykmnjkpl iwdmxcslbq (uiyfxadcrl ) View more	Positive	02 Jun 2016
				marizomib	(llurfmclxh) = rdmikmyide iwdmxcslbq (uiyfxadcrl ) View more
ASCO2015	Phase 1	Glioma	-	Marizomib	psnhshljig(ktzpulmval) = iftbdyyfeq yimhtdocgq (ocpscvieqt )	-	20 May 2015
ASCO2009	Phase 1	Solid tumor \| Lymphoma	39	NPI-0052	(tykdsdzsxq) = nftcblztyu hofkcxuatg (wlkftmmlht )	-	20 May 2009