Delving into the Latest Updates on BCG for Intravesical Instillation(China Medical System) with Synapse

Overview

Basic Info

Drug Type

Oncolytic bacteria, Live attenuated vaccine, Therapeutic vaccine

Synonyms-

Target-

Mechanism-

Therapeutic Areas

NeoplasmsUrogenital Diseases

Active Indication

Urothelial Carcinoma of the Urinary BladderBladder Cancer

Inactive Indication-

Originator Organization

medac Gesellschaft für klinische Spezialpräparate mbH

Active Organization

Shenzhen Kangzhe Pharmaceutical Co., Ltd.

medac Gesellschaft für klinische Spezialpräparate mbH

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

DE (02 Oct 2001),

Urothelial Carcinoma of the Urinary Bladder

Regulation-

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Author: Aben, Katja K H ; Netea, Mihai G ; van Puffelen, Jelmer H ; Kiemeney, Lambertus A L M ; Joosten, Leo A B ; Zuiverloon, Tahlita C M ; Oosterwijk, Egbert ; Witjes, J Alfred ; Oldenhof, Ursula T H ; Vermeulen, Sita H ; van Emst, Liesbeth ; Kooper, Denise ; Novakovic, Boris ; Vrieling, Alina ; Boormans, Joost L ; van der Heijden, Antoine G ; Galesloot, Tessel E

Background:

BCG is recommended as intravesical immunotherapy to reduce the risk of tumor recurrence in patients with non-muscle invasive bladder cancer (NMIBC). Currently, it is unknown whether intravesical BCG application induces trained immunity.

Methods:

The aim of this research was to determine whether BCG immunotherapy induces trained immunity in NMIBC patients. We conducted a prospective observational cohort study in 17 NMIBC patients scheduled for BCG therapy and measured trained immunity parameters at 9 time points before and during a 1-year BCG maintenance regimen. Ex vivo cytokine production by peripheral blood mononuclear cells, epigenetic modifications, and changes in the monocyte transcriptome were measured. The frequency of respiratory infections was investigated in two larger cohorts of BCG-treated and non-BCG treated NMIBC patients as a surrogate measurement of trained immunity. Gene-based association analysis of genetic variants in candidate trained immunity genes and their association with recurrence-free survival and progression-free survival after BCG therapy was performed to investigate the hypothesized link between trained immunity and clinical response.

Results:

We found that intravesical BCG does induce trained immunity based on an increased production of TNF and IL-1β after heterologous ex vivo stimulation of circulating monocytes 6–12 weeks after intravesical BCG treatment; and a 37% decreased risk (OR 0.63 (95% CI 0.40 to 1.01)) for respiratory infections in BCG-treated versus non-BCG-treated NMIBC patients. An epigenomics approach combining chromatin immuno precipitation-sequencing and RNA-sequencing with in vitro trained immunity experiments identified enhanced inflammasome activity in BCG-treated individuals. Finally, germline variation in genes that affect trained immunity was associated with recurrence and progression after BCG therapy in NMIBC.

Conclusion:

We conclude that BCG immunotherapy induces trained immunity in NMIBC patients and this may account for the protective effects against respiratory infections. The data of our gene-based association analysis suggest that a link between trained immunity and oncological outcome may exist. Future studies should further investigate how trained immunity affects the antitumor immune responses in BCG-treated NMIBC patients

01 Oct 2022·Alzheimer disease and associated disorders

Intravesical BCG and Incidence of Alzheimer Disease in Patients With Bladder Cancer

Article

Author: Bernick, Charles ; Makrakis, Dimitrios ; Wright, Jonathan L. ; Gore, John L. ; Holt, Sarah K. ; Grivas, Petros

Introduction::

Alzheimer disease (AD) is a common neurodegenerative disease, and immunomodulation offers treatment opportunities. Preclinical data suggest that intravesical Bacillus Calmette-Guerin (BCG) treatment could delay AD development. We investigated this relationship in a population-based cancer database.

Sample and Methods::

We queried the Surveillance, Epidemiology, and End Results-Medicare database for patients with high-risk nonmuscle-invasive bladder cancer (hrNMIBC). BCG dosage and subsequent Alzheimer diagnosis were collected through ICD-9/10 codes. Multivariable Cox regression was performed to assess the association between BCG therapy and subsequent Alzheimer diagnosis.

Results::

We identified 26,584 hrNMIBC patients; 51% received BCG and 8.3% were diagnosed with Alzheimer. BCG exposure was significantly associated with lower Alzheimer occurrence (hazard ratio: 0.73, P<0.05), which was dose-dependent. Increasing age, female sex, Black race, and increasing comorbidity index were significantly associated with a greater risk of subsequent Alzheimer diagnosis.

Discussion::

Treatment with intravesical BCG among patients with hrNMIBC was associated with a significantly lower risk for subsequent Alzheimer diagnosis, which seemed dose-dependent.

01 Dec 2018·CVIR endovascular

Mycotic aortic aneurysms post-Intravesical BCG treatment for early-stage bladder carcinoma

Article

Author: Bakshi, Darshan ; Mirakhur, Anirudh ; Moore, Randy D ; Wadhwani, Aman

BACKGROUND:

Intravesicular Bacillus Calmette-Guérin (BCG) is an effective adjunctive therapy for superficial bladder cancer that has been shown to delay recurrence and progression of disease. Serious side effects are relatively rare but are difficult to diagnose and are often overlooked. Vascular complications are particularly rare.

CASE PRESENTATION:

We report two cases of mycotic aortic aneurysms secondary to BCG treatment, one managed with endovascular stent-graft placement and the other with open surgical repair. The present understanding of disseminated BCGosis, including a literature review, will be discussed.

CONCLUSION:

The incidence of mycotic aneurysms from BCG treatment is rare and very few cases have been reported in the literature. These cases further expand the current knowledge on vascular complications related to BCG treatment. In the absence of formal guidelines, we recommend a multidisciplinary approach involving vascular surgery, diagnostic and interventional radiology, and infectious disease to manage these patients.

100 Deals associated with BCG for Intravesical Instillation(China Medical System)

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R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Urothelial Carcinoma of the Urinary Bladder	DE	medac Gesellschaft für klinische Spezialpräparate mbH	02 Oct 2001
Bladder Cancer	-	Shenzhen Kangzhe Pharmaceutical 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


AACR2023	Not Applicable	Non-Muscle Invasive Bladder Neoplasms	40	intravesical Bacillus Calmette-Guérin instillation (TERT C228T mutation)	fmeagsvgyh(byhesomshf) = fsmsbbfmex repzhqpcpl (somcsuhtpe )	-	04 Apr 2023
AACR2023	Not Applicable	Non-Muscle Invasive Bladder Neoplasms	40	intravesical Bacillus Calmette-Guérin instillation (KDM6A alteration)	fmeagsvgyh(byhesomshf) = pitgwdrjko repzhqpcpl (somcsuhtpe )	-	04 Apr 2023
MP82-18 (AUA2020)	Not Applicable	Non-Muscle Invasive Bladder Neoplasms	1,128	INTRAVESICAL BCG INSTILLATION (BCG instillation)	vsamslxsat(ilcjyxvkyv) = brughzugbs wlhykiciul (dfwzfotqhb ) View more	-	01 Apr 2020