Delving into the Latest Updates on AZD-5312 with Synapse

Overview

Basic Info

Drug Type

ASO

Synonyms

ARRx, ISIS ARRX, ISIS-ARRx

+ [9]

Target

AR-v7

Action

inhibitors

Mechanism

AR-v7 inhibitors(androgen receptor splice variant 7 inhibitors)

Therapeutic Areas

NeoplasmsUrogenital Diseases

Active Indication

Prostatic Cancer

Inactive Indication

Advanced Malignant Solid NeoplasmMetastatic castration-resistant prostate cancer

Originator Organization

Ionis

Active Organization

Ionis

AstraZeneca Pharmaceuticals Co. Ltd.

Inactive Organization

AstraZeneca PLC

Ionis Pharmaceuticals, Inc.

Suzhou Ribo Life Science Co., Ltd.

+ [2]

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure/Sequence

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主要研究目的 1) 确定ISIS 560131在中国AR V7阳性的mCRPC 患者的最大耐受剂量（MTD）以及II期推荐剂量（RP2D）。 2) 初步评价ISIS 560131在中国AR V7阳性的mCRPC患者的疗效。次要研究目的 1) 评价ISIS 560131在AR V7阳性的mCRPC 患者中的安全性和耐受性； 2) 评估ISIS 560131在AR-V7阳性的mCRPC患者的药代动力学特征； 3) 评价ISIS 560131的免疫原性； 4) 初步分析ISIS 560131在AR-V7阳性的mCRPC患者中的PK/PD关系。其他研究目的 1) 如数据允许，将分析AR受体表达情况及药物对信号通路调控基因的抑制；以及AR-V7不同检测方法的一致性； 2) 如数据允许，基于群体药代动力学（PopPK）分析方法，表征ISIS 560131在中国AR-V7阳性的mCRPC患者中的PK特征； 3) 如数据允许，评价ISIS 560131人体内暴露量与疗效和不良事件之间的关系。

[Translation]

Main study objectives 1) To determine the maximum tolerated dose (MTD) and phase II recommended dose (RP2D) of ISIS 560131 in Chinese patients with AR V7-positive mCRPC. 2) To preliminarily evaluate the efficacy of ISIS 560131 in Chinese patients with AR V7-positive mCRPC. Secondary study objectives 1) To evaluate the safety and tolerability of ISIS 560131 in patients with AR V7-positive mCRPC; 2) To evaluate the pharmacokinetic characteristics of ISIS 560131 in patients with AR-V7-positive mCRPC; 3) To evaluate the immunogenicity of ISIS 560131; 4) To preliminarily analyze the PK/PD relationship of ISIS 560131 in patients with AR-V7-positive mCRPC. Other research objectives 1) If data permit, analyze AR receptor expression and drug inhibition of signaling pathway regulatory genes; and the consistency of different detection methods for AR-V7; 2) If data permit, characterize the PK characteristics of ISIS 560131 in Chinese AR-V7-positive mCRPC patients based on population pharmacokinetic (PopPK) analysis methods; 3) If data permit, evaluate the relationship between ISIS 560131 exposure in humans and efficacy and adverse events.

Start Date24 Mar 2021

Sponsor / Collaborator

Suzhou Ribo Life Science Co., Ltd.

[+2]

ChiCTR2100044174

/ RecruitingPhase 2IIT

A Phase IIa Clinical Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of ISIS 560131 in Patients with Metastatic Castration-Resistant Prostate Cancer with Positive Androgen Receptor Splicing Variant 7 (AR-V7)

Start Date10 Mar 2021

Sponsor / Collaborator-

NCT03300505

/ TerminatedPhase 1IIT

ARRO-CITO: (UMCC 2017.055) Phase Ib/II Single-Arm Multi-Center Study of IONIS-AR-2.5Rx, a Next Generation Androgen Receptor Antisense Oligonucleotide, in Combination With Enzalutamide in Metastatic Castration Resistant Prostate Cancer

The purpose of this study is to test the effectiveness (how well the drug works), safety, and tolerability of the investigational drug combination of ARRx (also known as AZD5312) plus enzalutamide in patients with metastatic castration resistant prostate cancer.

Start Date31 May 2019

Sponsor / Collaborator

Rogel Cancer Center: University of Michigan

100 Clinical Results associated with AZD-5312

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100 Translational Medicine associated with AZD-5312

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100 Patents (Medical) associated with AZD-5312

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3

Literatures (Medical) associated with AZD-5312

22 Jan 2019·Expert Opinion on PharmacotherapyQ3 · MEDICINE

Perspectives on the current and emerging chemical androgen receptor antagonists for the treatment of prostate cancer

Q3 · MEDICINE

Review

Author: Papatsoris, Athanasios G. ; Dellis, Athanasios E.

INTRODUCTIONProstate cancer is the most common cancer in men. Regardless of the initial treatment of localized disease, almost all patients develop castration resistant prostate cancer (CRPC). A better understanding of the molecular mechanisms behind castration resistance has led to the approval of novel oral androgen receptor (AR) antagonists, such as enzalutamide and apalutamide. Indeed, research has accelerated with numerous agents being studied for the management of CRPC. Areas covered: Herein, the authors present currently used and emerging AR antagonists for the treatment of CRPC. Emerging agents include darolutamide, EZN-4176, AZD-3514, and AZD-5312, apatorsen, galeterone, ODM-2014, TRC-253, BMS-641988, and proxalutamide. Expert opinion: Further understanding of the mechanisms leading to castration resistance in prostate cancer can reveal potential targets for the development of novel AR antagonists. Current novel agents are associated with modest clinical and survival benefit, while acquired resistance and safety issues are under continuous evaluation. The combination of AR antagonists used and ideal sequencing strategies are key tasks ahead, along with the investigation of molecular biomarkers for future personalized targeted therapies. In the future, the challenge will be to determine an AR antagonist with the best combination of outcome and tolerability.

The American Journal of Managed Care

Rituximab Reference vs Biosimilar Utilization for Oncology vs Nononcology Indications

Article

Author: Johnson, Samuel G ; Winkler, Michelle ; Attridge, Rebecca L ; Elbeshbeshy, Rim A ; Labdi, Bonnie A

OBJECTIVESLimited data exist on the adoption of rituximab biosimilars vs the reference product by indication. Available data from real-world studies comparing rituximab biosimilar and reference use have focused predominantly on oncology indications. This is the first study to assess the utilization of the 3 US rituximab biosimilars vs the reference product.STUDY DESIGNComparative analysis.METHODSDeidentified real-world data of rituximab, rituximab-abbs, rituximab-pvvr, and rituximab-arrx dispensations between December 31, 2018, and February 1, 2022, were extracted using Trisus Medication Compare (The Craneware Group). The primary outcome was rituximab reference vs biosimilar utilization for oncology vs nononcology indications. Results were stratified by on-label and off-label use and treatment settings.RESULTSA total of 28,025 encounters were captured for rituximab and its biosimilars across 193 facilities (rituximab: n = 23,395; biosimilars, n = 4631 [rituximab-abbs: n = 2550; rituximab-pvvr, n = 2081; rituximab-arrx: n = 0]). Rituximab reference had higher dispensations for oncology (78.4%) and nononcology (88.3%) indications than its biosimilars (21.6% and 11.7%, respectively; P < .01). The 3-year annual trends from 2019 to 2021 revealed decreased rituximab reference utilization (99.99% to 40.1%) and increased biosimilar use (0.01% to 59.9%). Most oncology dispensations were on label (94.5%), whereas most nononcology dispensations were off label (73.6%; P < .01). A higher proportion of biosimilar use was attributed to on-label indications (67.7%; off-label, 32.2%) compared with rituximab reference (58.0% vs42.0%, respectively; P < .01). Nonacademic settings showed higher biosimilar adoption than academic settings (22.2% vs 10.3%, respectively; P < .01).CONCLUSIONSReal-world evidence shows an increase in rituximab biosimilar adoption over time, with higher adoption for oncology vs nononcology indications and in nonacademic settings.

Frontiers in MicrobiologyQ2 · BIOLOGY

Inhibitory Effects of Carbazomycin B Produced by Streptomyces roseoverticillatus 63 Against Xanthomonas oryzae pv. oryzae

Q2 · BIOLOGY

ArticleOA

Author: Shi, Tingting ; Zhu, Jiali ; He, Zhipeng ; Jiang, Donghua ; Hu, Lingming ; Guo, Xin

The present manuscript highlights the potential role of Streptomyces roseoverticillatus 63 (Sr-63) against Xanthomonas oryzae pv. oryzae (Xoo), which is the cause of a disastrous bacterial leaf blight disease with rice worldwide. The disease suppression was achieved under greenhouse conditions. A foliar spray of the fermentation broth of Sr-63 significantly reduced the leaf blight symptoms with rice in Xoo inoculated rice plants. Furthermore, we observed that the carbazomycin B, isolated from the fermentation broth of Sr-63, was demonstrated to have antibacterial activity against Xoo with a minimum inhibitory concentration (MIC) of 8 μg mL–1. The results indicated that carbzomycin B hampered the membrane formation of Xoo, reduced the production of xanthomonadin and extracellular polymeric substance (EPS). The fourier transform infrared spectroscopic (FT-IR) indicated that carbazomycin B changed the components of the cell membrane, then caused a change of the cell surface hydrophobicity of Xoo. Scanning electron microscopy revealed that the Xoo cells treated with carbazomycin B exhibited apparent structural deformation. The results also indicated that carbazomycin B had a negative impact on the metabolism of Xoo, carbazomycin B reduced the activity of malate dehydrogenase (MDH) activity and suppressed the protein expression of Xoo. Overall, our data suggests that Streptomyces roseoverticillatus 63 is a promising biocontrol agent that could be used to combat the bacterial leaf blight diseases of rice.

100 Deals associated with AZD-5312

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Prostatic Cancer	Phase 2	-	AstraZeneca Pharmaceuticals Co. Ltd.	-
Prostatic Cancer	Phase 2	-	Ionis	-
Metastatic castration-resistant prostate cancer	Preclinical	China	Ribo (HongKong) Life Science Limited	24 Mar 2021
Metastatic castration-resistant prostate cancer	Preclinical	China	PYRAMID Laboratories, Inc.	24 Mar 2021
Metastatic castration-resistant prostate cancer	Preclinical	China	Suzhou Ribo Life Science Co., Ltd.	24 Mar 2021
Solid tumor	Preclinical	United States	AstraZeneca PLC	-
Solid tumor	Preclinical	United Kingdom	AstraZeneca PLC	-
Advanced Malignant Solid Neoplasm	Discovery	United Kingdom	AstraZeneca PLC	01 May 2014
Advanced Malignant Solid Neoplasm	Discovery	United States	AstraZeneca PLC	01 May 2014