Delving into the Latest Updates on Drozitumab with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Anti-DR5 mAb(Genentech), Anti-Death Receptor 5 monoclonal antibody( Genentech), Anti-TRAIL Receptor-2 monoclonal antibody(Genentech)

+ [5]

Target

DR5

Action

agonists

Mechanism

DR5 agonists(Tumor necrosis factor receptor superfamily member 10B agonists)

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal Diseases

Active Indication

Breast Cancer

Inactive Indication

Advanced Lung Non-Small Cell CarcinomaCD20 positive Follicular LymphomaChondrosarcoma+ [1]

Originator Organization

Genentech, Inc.

Active Organization

University of AdelaideSloan-Kettering Institute for Cancer Research

Inactive Organization

Genentech, Inc.

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 75690L

Source: *****

Sequence Code 92381H

Source: *****

A Phase II, Single-Arm, Open-Label Study of the Safety, Pharmacokinetics, and Efficacy of Multiple Doses of PRO95780 Administered Intravenously in Combination With Rituximab in Patients With Follicular, CD20-Positive B-Cell Non-Hodgkin's Lymphoma That Has Progressed Following Previous Rituximab Therapy

This Phase II, single-arm, open-label, multicenter trial is designed to evaluate the safety, efficacy, and pharmacokinetics of PRO95780 when combined with rituximab in patients with follicular, CD20-positive B-cell NHL that has progressed following previous rituximab therapy.

Start Date01 Mar 2008

Sponsor / Collaborator

Genentech, Inc.

EUCTR2007-001666-32-BE

/ Not yet recruitingPhase 2

A PHASE II,SINGLE-ARM, OPEN-LABEL STUDY OF THE SAFETY,PHARMACOKINETICS, AND EFFICACY OF MULTIPLE DOSES OF APOMAB ADMINISTERED INTRAVENOUSLY IN COMBINATION WITH RITUXIMAB IN PATIENTS WITH FOLLICULAR, CD20-POSITIVE B-CELL NON-HODGKIN’S LYMPHOMA THAT HAS PROGRESSED FOLLOWING PREVIOUS RITUXIMAB THERAPY

Start Date26 Nov 2007

Sponsor / Collaborator

Genentech, Inc.

100 Clinical Results associated with Drozitumab

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100 Translational Medicine associated with Drozitumab

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100 Patents (Medical) associated with Drozitumab

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54

Literatures (Medical) associated with Drozitumab

01 Dec 2024·Journal of Controlled Release

Combination of multivalent DR5 receptor clustering agonists and histone deacetylase inhibitors for treatment of colon cancer

Article

Author: Galang, Jacob ; Sima, Monika ; Yang, Jiyuan ; Kopeček, Jindřich ; Li, Jiahui ; Al Faruque, Hasan ; Hu-Lieskovan, Sophia ; Arnold, Jaden

Death Receptor 5 (DR5) targeted therapies offer significant promise due to their pivotal role in mediating the extrinsic pathway of apoptosis. Despite DR5 overexpression in various malignancies and the potential of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), clinical applications of anti-DR5 monoclonal antibodies (mAbs) have been hampered by suboptimal outcomes potentially due to lack of receptor clustering. To address the limitation, we developed N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-based conjugates integrating multiple copies of DR5-targeting peptide (cyclic WDCLDNRIGRRQCVKL; cDR5) to enhance receptor clustering and apoptosis. Three conjugates with variable number of cDR5 were prepared and denoted as P_H-cDR5 (high valence), P_M-cDR5 (medium valence) and P_L-cDR5 (low valence). Our studies in TRAIL-sensitive and resistant cancer cell lines demonstrated that the HPMA copolymer-peptide conjugates (P-cDR5) significantly improved DR5 receptor clustering and induced apoptosis effectively. In TRAIL-sensitive colon cancer cells (COLO205, HCT-116), P-cDR5 showed efficacy comparable to anti-DR5 mAb Drozitumab (DRO), but P-cDR5 outperformed DRO in TRAIL-resistant cells (HT-29), highlighting the importance of efficient receptor clustering. In COLO205 cells P_M-cDR5 exhibited an IC50 of 94 pM, while P_H-cDR5 had an even lower IC50 of 15 pM (based on cDR5 equivalent concentration), indicating enhanced potency of the multivalent HPMA copolymer-based system with a flexible polymer backbone in comparison with the IC₅₀ for TRAIL at 0.12 nM. Combining P-cDR5 with valproic acid, a histone deacetylase inhibitor, resulted in further enhancement of apoptosis inducing efficacy, along with destabilizing mitochondrial membranes and increased sensitivity of TRAIL-resistant cells. These findings suggest that attaching multiple cDR5 peptides to a flexible water-soluble polymer carrier not only overcomes the limitations of previous designs but also offers a promising avenue for treating resistant cancers, pointing toward the need for further preclinical exploration and validation of this innovative strategy.

01 Nov 2023·ERJ Open Research

Benralizumab in severe eosinophilic asthma in real life: confirmed effectiveness and contrasted effect on sputum eosinophiliaversusexhaled nitric oxide fraction – PROMISE

Article

Author: Pottier, Laurence ; Schleich, Florence ; Paulus, Virginie ; Guissard, Françoise ; Tombu, Sophie ; Ziant, Stéphanie ; Kempeneers, Céline ; Donneau, Anne-Françoise ; Louis, Renaud ; Sanchez, Carole ; Rogister, Florence ; Seidel, Laurence ; Poirrier, Anne-Lise ; Moermans, Catherine ; Henket, Monique ; Louis, Gilles

BackgroundRandomised controlled trials have shown that benralizumab, an anti-interleukin-5 receptor monoclonal antibody, reduces exacerbations and oral corticosteroid dose and improves asthma control and lung function in severe eosinophilic asthma. The aim of this study was to confirm results of randomised controlled trials in real life in a population of 73 patients with severe eosinophilic asthma treated with benralizumab for at least 12 months.MethodsPatients underwent careful monitoring of asthma exacerbations, exhaled nitric oxide fraction, lung function, asthma control and quality of life questionnaire responses and sputum induction, and gave a blood sample at baseline, after 6 months and then every year.ResultsWe found significant reductions in exacerbations (by 92%, p<0.0001) and oral corticosteroid dose (by 83%, p<0.001) after 6 months that were maintained over time, with 78% of patients able to stop oral corticosteroid therapy. Patients improved their Asthma Control Test (ACT) score (from 11.7±5.1 to 16.9±5.35, p<0.0001), Asthma Control Questionnaire (ACQ) score (from 2.88±1.26 to 1.77±1.32, p<0.0001) and Asthma Quality of Life Questionnaire score (+1.04, p<0.0001) at 6 months and this was maintained during follow-up. Only 35% and 43% of patients reached asthma control according to an ACT score ≥20 and ACQ score <1.5, respectively. We observed stable post-bronchodilation lung function over time and a significant reduction in sputum eosinophil count, with 85% of patients exhibiting sputum eosinophil counts <3% after 6 months (p<0.01) with no effect on exhaled nitric oxide fraction.ConclusionIn our real-life study, we confirm the results published in randomised controlled trials showing a sharp reduction in exacerbations and oral corticosteroid therapy, an improvement in asthma control and quality of life, and a dramatic reduction in sputum eosinophil count.

01 Jan 2023·International Archives of Allergy and Immunology

Effect of Benralizumab on Mucus Plugs in Severe Eosinophilic Asthma

Article

Author: Shima, Kenjiro ; Koya, Toshiyuki ; Murai, Yui ; Watanabe, Satoshi ; Aoki, Ami ; Kikuchi, Toshiaki ; Kimura, Yosuke ; Sakai, Natsumi ; Tanaka, Kentaro ; Naramoto, Shun ; Tsubokawa, Fumito ; Hasegawa, Takashi

Introduction: Mucus plugs are associated with airway obstruction in severe asthma and are involved in the formation of activated eosinophils. Benralizumab, an anti-interleukin-5 receptor antibody, markedly reduces not only peripheral blood eosinophils but also airway eosinophils; however, its effects on mucus plugs have not been clarified. In this study, we examined the efficacy of benralizumab on mucus plugs using computed tomography (CT) imaging. Methods: Twelve patients who were administered benralizumab and underwent CT before and approximately 4 months after the introduction of benralizumab were included in this study, and the number of mucus plugs before and after benralizumab administration was compared. The correlation between the clinical background and treatment effect was also examined. Results: The number of mucus plugs significantly decreased after the introduction of benralizumab. The number of mucus plugs was correlated with sputum eosinophil percentage and eosinophil cationic protein in the sputum supernatants and inversely correlated with forced expiratory volume in 1 s (FEV1). Benralizumab induction resulted in a marked decrease in blood and sputum eosinophil levels and a significant improvement in asthma symptoms, quality of life scores, FEV1, and exacerbation frequency. Furthermore, there was a significant correlation between the reduction in mucus plugs and changes in the symptom score or FEV1. Discussion/Conclusion: These data suggest that benralizumab may have the potential to improve symptoms and respiratory function in patients with severe eosinophilic asthma by reducing mucus plugs.

100 Deals associated with Drozitumab

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External Link

KEGG	Wiki	ATC	Drug Bank
D09888	Drozitumab	-	DB15022

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Chondrosarcoma	Phase 2	United States	Genentech, Inc.	31 May 2007
Chondrosarcoma	Phase 2	Australia	Genentech, Inc.	31 May 2007
Breast Cancer	Preclinical	United States	Sloan-Kettering Institute for Cancer Research	01 May 2009
Breast Cancer	Preclinical	Australia	University of Adelaide	01 May 2009
CD20 positive Follicular Lymphoma	Discovery	-	Genentech, Inc.	01 Mar 2008
Metastatic Colorectal Carcinoma	Discovery	-	Genentech, Inc.	01 Oct 2007
Advanced Lung Non-Small Cell Carcinoma	Discovery	-	Genentech, Inc.	01 Jun 2007

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASCO_GI2011	Phase 1	Metastatic Colorectal Carcinoma	20	Drozitumab + Cetuximab + Irinotecan	(qdnabnobxt) = oeqkneeoey wsuulothbj (qmjrrnoxmk ) View more	-	01 Feb 2011
				Drozitumab + FOLFIRI	(zknafdzocy) = pwnkbvbvqs nhhcwcrfqp (xyagdwqcbf )

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Translational Medicine

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Deal

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Clinical Trial

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Approval

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Biosimilar

Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

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Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

Regulation

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Drozitumab

Overview

Basic Info

Structure/Sequence

Related

External Link

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Biosimilar

Regulation