A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Phase 2b Study to Assess the Safety and Efficacy of IGV-001, an Autologous Cell Immunotherapy With Antisense Oligonucleotide (IMV-001) Targeting IGF-1R, in Newly Diagnosed Patients With Glioblastoma

The purpose of this study is to assess progression-free survival (PFS) and overall survival (OS) in newly diagnosed Glioblastoma (GBM) participants treated with IGV-001 as compared with placebo.

开始日期2023-03-20

申办/合作机构

ImVax, Inc.初创企业

NCT02507583 / Completed临床1期IIT

Phase I Study in Humans Evaluating the Safety of Rectus Sheath Implantation of Diffusion Chambers Encapsulating Autologous Malignant Glioma Cells Treated With Insulin-like Growth Factor Receptor-1 Antisense Oligodeoxynucleotide (IGF-1R/AS ODN) in 32 Patients With Newly Diagnosed Malignant Glioma

This human Phase 1 trial is a continuation of a Phase 1 trial which enrolled patients with recurrent gliomas (#TJU-14379-101) and which was designed after a previously conducted Phase 1 human trial at our institution. With certain modifications, it is intended to reproduce the safety results of the recurrent glioma previous trials as well as explore any objective clinical responses in newly diagnosed patients. Protocol 14379-101 is closed to accrual and Abbreviated Clinical Report is prepared for FDA submission. The safety profile for this protocol was quite favorable.
This treatment involves taking the patient's own tumor cells at surgery, treating them with an investigational new drug (an antisense molecule) designed to shut down a targeted surface receptor protein, and re-implanting the cells, now encapsulated in small diffusion chambers the size of a nickel in the patient's abdomen within 24 hours after the surgery. Loss of the surface receptor causes the tumor cells to die in a process called apoptosis. As the tumor cells die, they release small particles called exosomes, each full of tumor antigens. The investigators believe that these exosomes as well as the presence of the antisense molecule work together to activate the immune system against the tumor as they slowly diffuse out of the chamber. Immune cells are immediately available for activation outside of the chamber because a wound was created to implant these tumor cells and a foreign body (the chamber) is present in the wound. In this trial, a dose escalation of the therapeutic agent will involve an increase in both biodiffusion chamber number as well as the time the biodiffusion chambers remain implanted. The wound and the chamber fortify the initial immune response which eventually leads to the activation of immune system T cells that attack and eliminate the tumor. By training the immune system to recognize the tumor, the patient is also protected through immune surveillance from later tumor growth should the tumor recur. Compared to treatment alternatives for tumor recurrence, including a boost of further radiation and more chemotherapy, this treatment represents potentially greater benefit with fewer risks.

开始日期2015-09-01

申办/合作机构

Thomas Jefferson University

NCT02064829 / CompletedN/A

An Open-label, Randomized, Multi-center, Single-Dose, 2-Sequence, 2-Period, Crossover, Comparative Bioequivalence Study of IG-001 (Cb-paclitaxel) 260 mg/m2 Versus Nab-paclitaxel 260 mg/m2 Administered Intravenously With an Open-Label Extension of IG-001 in Patients With Metastatic or Locally Recurrent Breast Cancer

The purpose of this study is to demonstrate bioequivalence of IG-001 versus nab-paclitaxel in female patients with metastatic or locally recurrent breast cancer. In addition, the study will compare the safety and tolerance of IG-001 and nab-paclitaxel during the bioequivalence 2-period crossover portion of the study. The study will also evaluate the long-term safety of IG-001 over repeated cycles, up to 4 additional cycles of administration.

开始日期2014-03-01

申办/合作机构

Sorrento Therapeutics, Inc.

100 项与 IGV-001 相关的临床结果

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100 项与 IGV-001 相关的转化医学

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100 项与 IGV-001 相关的专利（医药）

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项与 IGV-001 相关的文献（医药）

2023-11-29·Journal of neuro-oncology

Targeted immunotherapy for glioblastoma involving whole tumor-derived autologous cells in the upfront setting after craniotomy.

Review

作者: Carrie E Andrews ; Jenny Zilberberg ; Raul Perez-Olle ; Mark A Exley ; David W Andrews

PURPOSE:

To date, immunotherapeutic approaches in glioblastoma (GBM) have had limited clinical efficacy as compared to other solid tumors. Here we explore autologous cell treatments that have the potential to circumvent treatment resistance to immunotherapy for GBM.

METHODS:

We performed literature review and assessed clinical outcomes in phase 1 safety trials as well as phase 2 and 3 autologously-derived vaccines for the treatment of newly-diagnosed GBM. In one recent review of over 3,000 neuro-oncology phase 2 and phase 3 clinical trials, most trials were nonblinded (92%), single group (65%), nonrandomized (51%) and almost half were GBM trials. Only 10% involved a biologic and only 2.2% involved a double-blind randomized trial design.

RESULTS:

With this comparative literature review we conclude that our autologous cell product is uniquely antigen-inclusive and antigen-agnostic with a promising safety profile as well as unexpected clinical efficacy in our published phase 1b trial. We have since designed a rigorous double-blinded add-on placebo-controlled trial involving our implantable biologic drug device. We conclude that IGV-001 provides a novel immunotherapy platform for historically intransigent ndGBM in this ongoing phase 2b trial (NCT04485949).

2023-08-01·Journal for immunotherapy of cancer

A biologic-device combination product delivering tumor-derived antigens elicits immunogenic cell death-associated immune responses against glioblastoma.

Article

作者: Christopher Cultrara ; Christopher Uhl ; Kenneth Kirby ; Essam Abed Elrazaq ; Amelia Zellander ; David W Andrews ; Charles B Scott ; Lorenzo Galluzzi ; Mark A Exley ; Jenny Zilberberg

BACKGROUND:

IGV-001 is a personalized, autologous cancer cell-based immunotherapy conceived to deliver a tumor-derived antigenic payload in the context of immunostimulatory signals to patients with glioblastoma (GBM). IGV-001 consists of patient-derived GBM cells treated with an antisense oligodeoxynucleotide against insulin-like growth factor 1 receptor (IGF1R) and placed in proprietary biodiffusion chambers (BDCs). The BDCs are then exposed to 5-6 Gy radiation and implanted at abdominal sites for ~48 hours. IGV-001 has previously been shown to be generally safe with promising clinical activity in newly diagnosed GBM patients.

METHODS:

Mouse (m) or human (h) variants of IGV-001 were prepared using GL261 mouse GBM cells or human GBM cells, respectively. BDCs containing vehicle or mIGV-001 were implanted in the flanks of C57BL/6 albino female mice in preventative and therapeutic experiments, optionally in combination with a programmed cell death 1 (PD-1) blocker. Bioactivity of the general approach was also measured against hepatocellular carcinoma Hepa 1-6 cells. Mice were followed for the growth of subsequently implanted or pre-existing tumors and survival. Draining lymph nodes from mice receiving mIGV-001 were immunophenotyped. mIGV-001 and hIGV-001 were analyzed for extracellular ATP and high mobility group box 1 (HMGB1) as indicators of immunogenic cell death (ICD), along with flow cytometric analysis of viability, surface calreticulin, and reactive oxygen species. Stress and cell death-related pathways were analyzed by immunoblotting.

RESULTS:

IGV-001 causes oxidative and endoplasmic reticulum stress in GL261 cells, resulting in a cytotoxic response that enables the release of antigenic material and immunostimulatory, ICD-associated molecules including ATP and HMGB1 from BDCs. Immunophenotyping confirmed that IGV-001 increases the percentage of dendritic cells, as well as effector, and effector memory T cells in BDC-draining lymph nodes. Consistent with these observations, preventative IGV-001 limited tumor progression and extended overall survival in mice intracranially challenged with GL261 cells, a benefit that was associated with an increase in tumor-specific T cells with effector features. Similar findings were obtained in the Hepa 1-6 model. Moreover, therapeutically administered IGV-001 combined with PD-1 delayed progression in GBM-bearing mice.

CONCLUSIONS:

These results support treatment with IGV-001 to induce clinically relevant ICD-driven anticancer immune responses in patients with GBM.

2021-01-26·Clinical cancer research : an official journal of the American Association for Cancer Research1区 · 医学

Phase 1b Clinical Trial of IGV-001 for Patients with Newly Diagnosed Glioblastoma.

1区 · 医学

Article

作者: David W Andrews ; Kevin Judy ; Charles B Scott ; Samantha Garcia ; Larry A Harshyne ; Lawrence C Kenyon ; Kiran Talekar ; Adam Flanders ; Kofi-Buaku Atsina ; Lyndon Kim ; Nina Martinez ; Wenyin Shi ; Maria Werner-Wasik ; Haisong Liu ; Michael Prosniak ; Mark T Curtis ; Rhonda B Kean ; Donald Yandong Ye ; Emily Bongiorno ; Sami Sauma ; Mark A Exley ; Kara Pigott ; Douglas Craig Hooper

PURPOSE:

Despite standard of care (SOC) established by Stupp (2005), glioblastoma remains a uniformly poor prognosis. We evaluated IGV-001, which combines autologous glioblastoma tumor cells and an antisense oligonucleotide against insulin-like growth factor type 1 receptor (IMV-001), in newly diagnosed glioblastoma.

EXPERIMENTAL DESIGN:

This open label protocol was approved by the IRB at Jefferson. Tumor cells collected during resection were treated ex vivo with IMV-001, encapsulated in biodiffusion chambers with additional IMV-001, irradiated, then implanted in abdominal acceptor sites. Patients were randomized to four exposure levels and SOC was initiated 4-6 weeks later. Based on clinical improvements, randomization was halted after patient 23 and subsequent patients received only the highest exposure. Safety and tumor progression were primary and secondary objectives, respectively. Time-to-event outcomes were compared to the SOC arms of published studies.

RESULTS:

Thirty-three patients were enrolled and median follow-up was 3.1 years. Six patients had adverse events (grade {less than or equal to}3) possibly related to IGV-001. Median progression-free survival (PFS) was 9.8 months in the intent-to-treat population (vs. SOC, 6.5 months; P=.0003). In IGV-001-treated patients who met Stupp-eligible criteria, PFS was 11.6 months overall (n=22; P=.001) and 17.1 months at the highest exposure (n=10; P=.0025). The greatest overall survival was observed in Stupp-eligible patients receiving the highest exposure (median, 38.2 months; P=.044). Stupp-eligible patients with methylated O6-methylguanine-DNA methyltransferase promoter (n=10) demonstrated median PFS of 38.4 months (P=.0008). Evidence of immune activation was noted.

CONCLUSIONS:

IGV-001 was well-tolerated, PFS compared favorably to SOC, and evidence suggested an immune-mediated mechanism. (Clinicaltrials.gov NCT02507583).

项与 IGV-001 相关的新闻（医药）

2023-11-20

·BioSpace

Imvax Presents New Data at 2023 SNO Annual Meeting Supporting its Lead Program, IGV-001, in Newly Diagnosed Glioblastoma

PHILADELPHIA--(BUSINESS WIRE)-- Imvax, Inc., a clinical-stage biotechnology company developing personalized, whole tumor-derived immunotherapies, today announced details of its two poster presentations at the 2023 Society for NeuroOncology (SNO) 28th Annual Meeting, which was held in Vancouver, British Columbia, Canada, from November 15-19, 2023. At the meeting, Imvax presented new data from its Phase 1b study of IGV-001 in patients with newly diagnosed glioblastoma (ndGBM). Ian Y. Lee, M.D., Neurosurgeon, Henry Ford Health System, also presented information relating to Imvax’s ongoing randomized, multicenter, double-blind, placebo-controlled Phase 2b clinical trial of IGV-001 in patients with ndGBM. “These presentations highlight the importance of the Phase 1b results to the IGV-001 program and reflect the rigor of the design of the ongoing Phase 2b trial,” said David W. Andrews, M.D., Chief Medical Officer of Imvax. “I’m pleased to report that the Phase 2b study is enrolling well, and we expect to complete enrollment in the first half of 2024.” The first poster presentation, entitled “Additional results from a Phase 1b study of IGV-001 in patients with newly diagnosed glioblastoma,” highlights a statistically significant correlation in Imvax’s Phase 1b study of IGV-001 between progression free survival (PFS) and overall survival (OS) in the intent-to-treat (ITT) study population, suggesting the use of median PFS as an end point in future ndGBM clinical trials. Additional data presented highlighted a significant decrease at various study points of the average neutrophil-to-lymphocyte (NLR) ratio. The NLR may be a potential biomarker for positive clinical outcomes, which will be further explored as part of Imvax’s ongoing Phase 2b study in ndGBM patients. The second poster presentation, entitled “A randomized, multicenter, double-blind, Phase 2b study of IGV-001, an autologous cell immunotherapy with antisense oligo IMV-001 targeting IGF-1R, vs placebo, in newly diagnosed glioblastoma patients,” described the ongoing Phase 2b trial (NCT04485949) including study objectives, design, endpoints, locations, and key inclusion and exclusion criteria. About IGV-001 IGV-001 is an autologous biologic-device combination product derived from Imvax’s proprietary Goldspire™ immuno-oncology platform for solid tumors, which involves a unique approach to inducing a broad and durable immune response against tumors. Phase 1 studies showed that IGV-001 was safe and well tolerated, and a Phase 1b ndGBM study also yielded several efficacy signals, including significant improvements in PFS, OS, radiographic evidence of tumor response, and multiple biomarker changes that supported the presence of an immune response (Andrews DW, et al., Clin Cancer Res. 2021;27(7):1912-1922). In ten Stupp-eligible ndGBM patients in the highest dose cohort treated with IGV-001, median PFS was 17.1 months, compared with 6.5 months in historical standard-of-care (SOC) treatment, and median OS was 38.2 months, compared with 16.2 months in historical SOC. About Imvax, Inc. Imvax is a clinical-stage biotechnology company with a unique platform technology, Goldspire™, focused on delivering personalized, whole tumor-derived immunotherapies across a range of solid tumors. Imvax’s most advanced program, IGV-001, is currently being evaluated in a Phase 2b clinical trial in newly diagnosed glioblastoma patients. Imvax’s portfolio also includes several other programs designed to stimulate a patient’s immune system against the entire antigen signature of their tumor. Imvax is headquartered in Philadelphia, PA. For additional information, please visit .

免疫疗法临床结果临床1期ASCO会议临床2期

2023-11-10

·BioSpace

Imvax to Present New Data on Lead Program, IGV-001, at 2023 SNO Annual Meeting

PHILADELPHIA--(BUSINESS WIRE)-- Imvax, Inc., a clinical-stage biotechnology company developing personalized, whole tumor-derived immunotherapies, today announced two poster presentations at the 2023 Society for NeuroOncology (SNO) 28th Annual Meeting in Vancouver, British Columbia, Canada, from November 15-19, 2023. At the meeting, Imvax will present new data from its Phase 1b study of IGV-001 in patients with newly diagnosed glioblastoma (ndGBM), as well as information relating to the company’s ongoing randomized, multicenter, double-blind, placebo-controlled Phase 2b clinical trial of IGV-001 in patients with ndGBM. On Friday, November 17, 2023, at 12:45 p.m. PT, Brad Elder, M.D., Director, Neurosurgical Oncology, and Associate Professor, Department of Neurological Surgery at The Ohio State University Wexner Medical Center, will present an Independent Support Session focused on the development of IGV-001 for the treatment of ndGBM. The details of the two poster presentations are below: Title: “Additional results from a Phase 1b study of IGV-001 in patients with newly diagnosed glioblastoma” Number: CTIM-17 Timing: November 17, 2023, 7:30 p.m. – 9:30 p.m. PT Presenter: Raul Perez-Olle, M.D., Ph.D. Title: “A randomized, multicenter, double-blind, Phase 2b study of IGV-001, an autologous cell immunotherapy with antisense oligo IMV-001 targeting IGF-1R, vs placebo, in newly diagnosed glioblastoma patients” Number: RTID-08 Timing: November 17, 2023, 7:30 p.m. – 9:30 p.m. PT Presenter: Ian Y. Lee, M.D. About Imvax, Inc. Imvax is a clinical-stage biotechnology company with a unique platform technology, Goldspire™, focused on delivering personalized, whole tumor-derived immunotherapies across a range of solid tumors. Imvax’s most advanced program, IGV-001, is currently being evaluated in a Phase 2b clinical trial in newly diagnosed glioblastoma patients. Imvax’s portfolio also includes several other programs designed to stimulate a patient’s immune system against the entire antigen signature of their tumor. Imvax is headquartered in Philadelphia, PA. For additional information, please visit .

临床2期免疫疗法ASCO会议临床结果

2023-08-29

·生物制品圈

盘点 | 全球小核酸药物临床Ⅱ/Ⅲ期试验概况

近年来FDA已批准了多款小核酸药物，主要用于治疗罕见病。截至2023年，全球小核酸药物进入临床管线的共有近80个，覆盖神经、心血管、感染和肿瘤等领域，共计有 15 款小核酸药物获批上市。但有2款早期ASO药物与1款适配体药物由于销售额过低等原因而退市，目前仍在市场的有7款ASO、5款siRNA药物。上市小核酸药物已在盘点｜小核酸药物的详细分类及上市情况中详细总结，感兴趣的朋友可以点击链接查阅，本文接着盘点小核酸药物在Ⅲ期/Ⅱ期临床阶段的进展情况。图注：全球已上市小核酸药物（含已退市） 01 全球小核酸药物Ⅲ期临床概览图注：全球小核酸药物Ⅲ期临床概览1.1 TivanisiranSylentis推出的Tivanisiran (SYL1001) 是一种 siRNA，用于干眼症的治疗。干眼症（DED）的特征是泪膜改变，伴有眼部炎症和神经感觉异常，这种情况的主要临床症状是泪液不稳定和眼损伤。Tivanisiran 用于沉默瞬时受体电位香草素1（TRPV1） mRNA。Tivanisiran 旨在减少眼部不适和疼痛，并被证明可以改善人类和动物模型中的眼充血和泪液质量。目前Tivanisiran处在Ⅲ期试验阶段，评估治疗治疗干眼症以及干燥综合征引起的干眼症的安全性，研究预计在2023年下半年到2024年上半年完成（NCT05310422；NCT04819269）。1.2 BepirovirsenGSK推出的Bepirovirsen作为用于治疗乙型肝炎的ASO治疗药物，Ⅱ期临床结果显示可降低乙型肝炎表面抗原（HBsAg）和乙型肝炎病毒（HBV）DNA的水平。乙型肝炎病毒利用这些RNA在受感染肝细胞中自我复制，产生病毒抗原（蛋白），而生成的病毒抗原能帮助病毒逃脱免疫系统清除，从而促使乙型肝炎疾病慢性化。ASO通过招募肝脏自身的酶将病毒RNA降解成无活性形式并将其清除。RNA水平降低使病毒和肝细胞生成的HBsAg均减少。Bepirovirsen具有通过Toll样受体8（TLR8）刺激免疫应答的特性，这可能有助于免疫系统持久清除血液循环系统中的病毒。对于Bepirovirsen有效性和安全性的Ⅲ期临床试验预计在2026年初结束（NCT05630807；NCT05630820）。1.3 Leqvio®（Inclisiran） Novartis Pharma GmbH诺华制药公司推出的Leqvio®(Inclisiran)，作为饮食控制的一种辅助手段，用于治疗成人原发性高胆固醇血症（杂合子家族性和非家族性）或混合型血脂异常。Leqvio是一款siRNA疗法。使用该药可以持续降低患者LDL-C引起的心血管疾患的发病率。Leqvio可与编码PCSK9蛋白的mRNA结合，通过RNA的干扰作用来防止肝脏生成PCSK9蛋白。PCSK9蛋白的作用是抑制LDL受体的回收和再利用。而降低体内PCSK9的水平可以让更多LDL受体回到肝细胞表面，与更多LDL结合，进而将它们从血液中清除。目前此药正在进行一项Ⅲ期临床实验以评估对已确诊心血管疾病（CVD）参与者的主要不良心血管（MACE）事件的益处。预计在2027年完成（NCT05004675）。1.4 Oxlumo®（Lumasiran）由Alnylam研发的Lumasiran 于2020年11月23日被FDA批准上市作为首个治疗原发性高草酸尿1型（PH1）的药物。PH1是一种罕见的遗传性疾病。Oxlumo获得孤儿药称号和突破性治疗指定。Lumasiran是一种靶向HAO1的siRNA，与含有N-乙酰半乳糖胺的配体共价连接，通过RNAi靶向肝细胞中的羟基酸氧化酶1 (HAO1)的mRNA，从而降低乙醇酸氧化酶(GO)酶的水平。GO酶水平的降低可以降低乙醛酸的可利用量，乙醛酸是产生草酸的底物。由于谷氨酸脱羧酶位于导致PH1的丙氨酸：乙醛酸氨基转移酶(AGT)缺陷酶的上游，Lumasiran的作用机制与潜在的AGXT基因突变无关。此药目前正在进行多项Ⅲ期临床试验（NCT04152200；NCT04152200），旨在评估 Lumasiran 在原发性高草酸尿症 1 型婴幼儿、儿童、成人以及晚期原发性PH1患者中的疗效、安全性、药代动力学和药效学。1.5 QR-110QR-110 是一种基于 RNA 的寡核苷酸，旨在解决 CEP290 基因中 p.Cys998X 突变引起的Leber先天性黑朦10（LCA10）的根本原因。LCA是儿童遗传病导致的失明的最常见原因，由一组疾病组成，其中LCA 10是更严重的形式之一。p.Cys998X突变是前mRNA中一个核苷酸的取代，导致mRNA和非功能性CEP290 mRNA的异常剪接。QR-110 旨在恢复正常（野生型）CEP290 mRNA，通过结合前 mRNA 中的突变位置导致前 mRNA 正常剪接，从而产生正常的 CEP290 蛋白。ProQR Therapeutics正在进行一项双盲、随机、对照、多剂量Ⅱ/Ⅲ期临床研究，目的是评估通过玻璃体内注射给予的QR-110在治疗 LCA受试者的疗效、安全性、耐受性和全身暴露。1.6 UltevursenProQR Therapeutics正在进行关于Ultevursen（以前称为QR-421a）的Ⅱ/Ⅲ期临床试验，本研究的目的是评估通过玻璃体内注射（IVT）给予Ultevursen的疗效安全性和耐受性，用于由于USH13A基因外显子2突变引起的视网膜色素变性（RP）受试者。此项研究预计在2024年完成。Ultevursen是一种基于单链 RNA的寡核苷酸，可以阻止因USH2A基因(编码 usherin 蛋白)的第13外显子突变而导致的色素性视网膜炎患者的视力下降。它通过眼睛玻璃体内注射给药，并已在美国和欧盟获得孤儿药指定，并获得了 FDA 的快速通道和罕见儿科疾病指定。研究预计在2024年底完成（NCT03913143；NCT04855045）。 02 全球小核酸药物Ⅱ期临床概览图注：全球小核酸药物Ⅱ期临床概览2.1 SYL1801SYL1801Ⅱ期临床试验由Sylentis公司发起。SYL1801是一种靶向NRARP（NOTCH Regulated Ankyrin Repeat Protein）的siRNA，使用Sylentis专有的SirFinderTM进行工程设计，用于预防和/或控制湿性年龄相关性黄斑变性（AMD）的进展。SYL1801作为滴眼液给药，以转录下调NRARP的表达，NRARP在控制视网膜中新血管生成中起重要作用，这与基于抗VEGF药物的常规抗血管生成疗法所针对的靶标不同。目前该药正在进行Ⅱ期临床招聘，该临床试验的目的是比较三种不同剂量的SYL1801滴眼液的安全性和对视力的影响，预计在2022年11月22日完成（NCT05637255）。2.2 ALN-HSD由Regeneron和Alnylam发起的关于ALN-HSD的Ⅱ期临床研究，ALN-HSD作为皮下注射 RNAi 治疗药物，靶向HSD17B13基因，用于治疗 NASH。此项研究以非酒精性脂肪性肝炎（NASH）患者为对象，旨在评估ALN-HSD在患有NASH伴有遗传危险因素的纤维化（NASHGEN-2）的成年患者中的疗效和安全性（NCT05519475）。NASH是非酒精性脂肪性肝病（NAFLD）的一种形式，当脂肪在肝细胞中积聚，损害它们，并使肝脏因纤维化（疤痕组织）而发炎和僵硬时，就会发生NASH。NASH可以进展为肝硬化（长期疤痕）和肝衰竭，预计2026年12月09日完成。2.3 OLX10010由OliX公司发起的一项随机、双盲、受试者内、安慰剂对照的Ⅱa期临床实验，评估OLX10010作为辅助疗法减少疤痕修复手术后肥厚性疤痕复发的疗效。OLX10010是一种穿透细胞的不对称siRNA（cp asiRNA），可干扰结缔组织生长因子（CTGF）的表达。这项研究的目的是确定OLX10010在减少肥厚性疤痕复发方面的疗效，该研究将评估疤痕整复手术后肥厚性疤痕的减少和复发情况。预计在2023年9月份完成（NCT04877756）。2.4 ALN-KHKALN-KHK是一种靶向酮己糖激酶（KHK）的研究性RNAi治疗药物，用于治疗2型糖尿病（T2DM）。ALN-KHK采用Alnylam的增强稳定化学增强型（ESC+）GalNAc偶联物技术，该技术能够以更高的选择性和广泛的治疗指数进行皮下给药。2型糖尿病是一种全球性疾病，影响着世界6%以上的人口，全世界的发病率和流行率正在上升，估计有超过450.55亿人受到影响。Alnylam于2023年3月发起随机、双盲、安慰剂对照、由两部分组成的Ⅰ/Ⅱ 期研究，研究单剂量 ALN-KHK 对肥胖成年健康志愿者超重和多剂量 ALN-KHK 在肥胖 2 型糖尿病患者中的安全性、耐受性、有效性、药代动力学和药效学。此项研究预计在2024年上半年完成（NCT05761301）。2.5 ALN-AGT01同样由Alnylam发起，以评估RNAi疗法药物ALN-AGT01在轻度至中度高血压（KARDIA-1）患者中的有效性和安全性的一项随机、双盲、安慰剂对照、剂量范围多中心研究Ⅱ 期研究正在开展，此项研究预计在2025年完成（NCT04936035）。2.6 SQY512023年4月份由SQY Therapeutics发起一项单中心、开放标签Ⅰ/Ⅱa 期研究，旨在评估 SQY51 在杜氏肌营养不良症患者中的安全性、药代动力学和药效学。杜氏肌营养不良症（DMD）是一种遗传性疾病，导致身体所有肌肉进行性退化。它是由位于X染色体上的DMD基因（突变）异常引起的，该基因编码肌营养不良蛋白，肌营养不良蛋白是一种对肌肉纤维正常运作至关重要的蛋白质。SQY51是一种反义寡核苷酸，旨在杂交到DMD基因的pre-mRNA转录本上的特定位点，以便在mRNA成熟（外显子跳跃）期间去除突变基因的某些元素，以恢复功能性截短肌营养不良蛋白的产生。SQY51使用“三环DNA”家族的非天然核苷酸，它们的优点是非常稳定，并且比天然对应物更有效地与RNA靶标杂交。12名患者(6岁以上)将被纳入试验。研究的第1阶段，将持续13周，他们都将接受6次递增剂量的 SQY51静脉注射。对于第2a 阶段，第1阶段的参与者将被分为3个队列，每个队列用不同剂量的 SQY51治疗32周，此项研究预计在2025年完成（NCT05753462）。图注：SQY51建模2.7 K3228836GlaxoSmithKline研发的ASO化合物GSK3228836，目前正在开展一项单盲、随机、对照的Ⅱ期研究，旨在量化序贯治疗的疗效，并确定序贯治疗相对于GSK3228836治疗在接受NA治疗的CHB患者中的附加值。此项研究从2022年3月份开始，预计2026年结束（NCT05276297）。2.8 STK-001Stoke Therapeutics推出的STK-001用于治疗儿童和青少年Dravet综合征。STK-001为一种反义寡核苷酸药物，有可能成为第一种针对Dravet综合征根本病因的改善性疗法。Dravet综合征是一种严重的进行性遗传性癫痫，特征表现为出生后一年内开始频繁、持续和难治性的癫痫发作。由于该疾病可导致相关发育迟缓和认知障碍，因此被归类为发育性和癫痫性脑病。STK-001通过利用SCN1A基因的非突变（野生型）拷贝来恢复生理性NaV1.1基因表达，进而上调NaV1.1蛋白的表达，从而减少癫痫发作和显著非发作性并发症的发生。Stoke目前的临床前数据已经证明STK-001的作用机制和概念。FDA已授予STK-001孤儿药称号，作为治疗Dravet综合征的新的潜在疗法。目前Stoke Therapeutics正在评估Dravet综合征患者单次和多次递增剂量STK-001的安全性和耐受性，预计2027年和2025年完成（NCT04740476；NCT04442295）。2.9 IGV-001Imvax目前正在进行一项随机、多中心、双盲、安慰剂对照的 Ⅱb 期研究，旨在评估 IGV-001（一种靶向 IGF-001R 的反义寡核苷酸（IMV-1）的自体细胞免疫疗法）在新诊断的胶质母细胞瘤（GBM）患者中的安全性和有效性。IGV-001是一款针对多形性胶质母细胞瘤的疫苗，由三种物质组成：患者的肿瘤细胞、IGF-1R反义寡核苷酸（IMV-001）、渗透室（ bio-diffusion chamber，其允许大分子渗出）。IGV-001首先从收集GBM患者手术切除的肿瘤细胞开始，然后经过IGF-1R反义寡核苷酸（IMV-001）处理，将肿瘤细胞推向受控细胞死亡。最后将这些处理过的细胞再次混合过量的IMV-001（作为佐剂）置于渗透室中，最后在手术后的24小时内植入患者的腹部。植入时间达到48小时后，将其取出，完成疫苗接种全过程。这一创新疫苗已经被美国FDA授予孤儿药资格。此项试验于2023年3月开始，预计2027年完成研究（NCT04485949）。2.10 BP1001 Bio-Path Holdings目前正在进行一项 IIa 期开放标签临床试验，旨在评估 BP1001（脂质体 Grb2 反义寡核苷酸）与维奈托克加地西他滨联合用于不适合强化诱导治疗的难治性/复发性急性髓性白血病（AML）患者的安全性、药代动力学、药效学和疗效。生长因子受体结合蛋白-2（Grb2）对癌基因信号传导和肿瘤进展至关重要。BP1001是一种脂质体掺入的Grb2反义寡核苷酸，可抑制Grb2表达。I/Ib 期单中心研究表明，BP1001 的安全性高达 90 mg/m2BP1001与低剂量阿糖胞苷（LDAC）联合治疗AML患者的剂量和疗效。本次研究的主要目的是评估：（1） BP1001 加维奈托克加地西他滨的组合是否比维奈托克加地西他滨在不能或选择不接受更高强度化疗的未经治疗的 AML 受试者中提供更大的疗效（完全缓解 [CR]、完全缓解伴不完全血液学恢复 [CRi]、完全缓解伴部分血液学恢复 [CRh]）;（2）基于BP1001的治疗是否比强化化疗（通过历史比较）对难治性/复发性AML的受试者提供更大的疗效（CR，CRi，CRh）。研究预计于2024年底结束（NCT04196257；NCT02781883）。2.11 QR-1123ProQR Therapeutics发起的一项前瞻性首次人体研究，评估 QR-1123 在因视紫红质（RHO）基因 P23H 突变而导致的常染色体显性视网膜色素变性（adRP）受试者中的安全性和耐受性。QR-1123是一种反义寡核苷酸，旨在特异性靶向突变型P23H mRNA，以选择性降低P23H蛋白的表达，同时保留野生型（WT）RHO蛋白的表达。据推测，突变P23H mRNA的减少将减少显性阴性蛋白的有害作用，并应导致WT视紫红质蛋白在光感受器中的功能增加。WT RHO功能的恢复有望改善因P23H突变引起的adRP患者的视力（NCT04123626）。2.12 PRAX-222Praxis Precision Medicines推出的PRAX-222是一种反义寡核苷酸，旨在选择性地降低SCN2A功能获得性癫痫患者SCN2A基因编码蛋白的表达水平。PRAX-222在体外研究中可降低SCN2A的基因表达和蛋白质的水平。在SCN2A小鼠模型中，PRAX-222可显著且剂量依赖性地减少小鼠癫痫发作、改善小鼠的行为和运动活动，并增加存活率，有望成为首个能够缓解该疾病的疗法。目前，PRAX-222已获得FDA的孤儿药资格和罕见儿科疾病资格，以及欧洲药品管理局（EMA）的用于治疗SCN2A-DEE的孤儿药资格。目前此药正在进行Ⅱ期临床试验，旨在研究多剂量PRAX-222在早发性SCN2A发育性和癫痫性脑病儿童参与者中的安全性和有效性（NCT05737784）。2.13 BNT112BNT112由信使核糖核酸（mRNA [或RNA]）组成，靶向在新生和转移性前列腺癌中表达的5种抗原，这些抗原分别与脂质体复合以形成血清稳定的RNA脂复合物（RNA-LPX）。BioNTech SE正在进行Ⅰ/Ⅱ期临床试验以评估 BNT112 癌症疫苗单药治疗或与西米普利单抗联合治疗转移性去势抵抗性前列腺癌（mCRPC：第 1 部分和第 2 部分 Arm 1A 和 1B）和高风险局部前列腺癌（LPC）患者的安全性、耐受性、免疫原性和初步疗效。此项研究预计在2023年下半年结束（NCT04382898）。2.14 mRNA-3705 & mRNA-3927mRNA-3705是一款治疗甲基丙二酸血症（MMA）的在研mRNA疗法，通过静脉输注给药，用于治疗因为甲基丙二酸单酰辅酶A变位酶（MUT）缺失引起的MMA患者。mRNA-3927旨在指导机体恢复导致丙酸血症（PA）的缺失或功能失调的蛋白质。旨在评估mRNA-3705的长期安全性和评估mRNA-3927对先前参加过研究mRNA-3927-P101（NCT04159103）的丙酸血症（PA）参与者施用mRNA-3927的长期安全性的Ⅱ期临床试验由ModernaTX公司发起，两项试验均预计在2030年以后收官（NCT05295433；NCT04899310）。2.15 Sapablursen由专注小核酸技术研发和创新技术的Ionis公司推出的Sapablursen，原名ISIS 702843，IONIS-TMPRSS6-LRx，是一种在研配体偶联反义（LICA）药物，旨在靶向TMPRSS6基因以调节铁调素的产生。铁调素是铁稳态的关键调节因子。通过调节铁调素的表达，Sapablursen有可能对以缺铁为特征的疾病产生积极影响，例如真性红细胞增多症（PV）。目前此药处于 Ⅱa 期临床研究阶段，研究旨在评估 Sapablursen用于静脉切开术依赖性真性红细胞增多症（PD-PV）患者的疗效、安全性、耐受性、药代动力学和药效学。研究预计在2025年初完成（NCT05143957）。小结除了以上15种处于Ⅱ期临床试验和6种Ⅲ期临床阶段的小核酸药物之外，还有近40种处于Ⅰ期临床研究阶段，涵盖siRNA、mRNA、ASO等。小核酸药物技术在企业分布上形成了两类具有代表性的企业，一类是专注小核酸技术研发和创新技术的公司，例如Ionis、Alnylam等，另一类是生物医药巨头公司通过合作开发布局小核酸药物领域，例如罗氏、阿斯利康、诺华等。小核酸药物具有靶向特异性强、药物作用长效、研发周期短、靶点丰富以及高效性，与传统药物相比，具有多重技术优势，多样化的研发模式也使得小核酸药物研发资源的使用更加高效。目前小核酸药物行业整体具有较高景气度、良好竞争格局、较大潜在市场规模的特性，逐步稳健快速发展。参考资料：1.Moreno-Montañés J, Bleau AM, Jimenez AI. Tivanisiran, a novel siRNA for the treatment of dry eye disease. Expert Opin Investig Drugs. 2018;27(4):421-426. doi:10.1080/13543784.2018.14576472.Girach A, Audo I, Birch DG, et al. RNA-based therapies in inherited retinal diseases. Therapeutic Advances in Ophthalmology. 2022;14. doi:10.1177/251584142211346023.Ana Isabel Jimenez, Veronica Ruz, Laura Rico, Tamara Martinez, Susana Monteiro, Ascension Cuesta, Amor Guerra, Alba Cuenca, Victoria Gonzalez; SYL1801: Preclinical Efficacy and Safety of a siRNA-based eye drops treatment for Age Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5389.

siRNA临床2期临床3期信使RNA寡核苷酸

100 项与 IGV-001 相关的药物交易

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研发状态

适应症	最高研发状态	国家/地区	公司
胶质母细胞瘤	临床2期	美国更多	ImVax, Inc.初创企业更多
实体瘤	临床前	美国更多	ImVax, Inc.初创企业更多

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


IG-001 phase 4 data in Korea (AACR2014)	临床4期	转移性乳腺癌	186	IG-001	(衊淵醖鬱遞淵襯鑰顧餘) = 襯窪齋膚觸廠醖鹽製構鏇糧壓顧夢廠選醖蓋築 (膚窪遞夢艱鬱齋積構繭 ) 更多	积极	2014-10-01
AACR2023	临床1期	胶质母细胞瘤 insulin-like growth factor 1-receptor	-	IGV-001	(築築襯膚鏇鑰窪遞製鏇) = 夢範鹹獵蓋鬱鏇衊網膚顧壓夢獵餘鬱艱鹹築鹹 (網築鏇鏇鹽艱膚鑰壓壓 )	-	2023-04-04
NCT02507583 (Pubmed \| Clin Cancer Res)	临床1期	胶质母细胞瘤	33	IGV-001	(繭膚壓醖獵鏇網鹽鹽廠) = Six patients had adverse events (grade ≤3) possibly related to IGV-001 觸衊鏇鹹醖鹽糧獵壓膚 (憲構簾鏇醖憲鑰夢鑰積 )	-	2021-01-26
				IGV-001 (Standard of care (SOC))
NCT04485949 (SNO2023) 人工标引	临床2期	胶质母细胞瘤一线	-	IGV-001	(襯鏇夢鏇齋遞構簾艱繭) = 艱鹽鹽憲壓糧選糧願繭鏇淵壓顧窪廠壓獵窪網 (蓋餘網艱夢積鹽網顧鹹 )	积极	2023-11-10
				Placebo	(襯鏇夢鏇齋遞構簾艱繭) = 餘憲襯選遞鹽壓選鑰衊鏇淵壓顧窪廠壓獵窪網 (蓋餘網艱夢積鹽網顧鹹 )
NCT02507583 (GlobeNewswire) 人工标引	临床1期	胶质母细胞瘤一线	33	Standard of Care+IGV-001	(築壓艱蓋壓艱簾鏇蓋繭) = 夢衊糧鹽築繭鏇鏇選鹹蓋餘鹹淵遞夢網壓壓鏇 (醖艱廠網顧鑰壓鬱衊願 ) 更多	积极	2019-03-31
				Standard of Care	(築壓艱蓋壓艱簾鏇蓋繭) = 淵鹽廠繭鏇壓餘繭鑰簾蓋餘鹹淵遞夢網壓壓鏇 (醖艱廠網顧鑰壓鬱衊願 ) 更多
AACR2013	N/A	肿瘤	-	IG-001	(獵淵積壓壓憲獵願網鬱) = 製衊鹹簾願繭壓網壓鏇獵鏇窪鹽艱網鹽鏇壓選 (鏇蓋製觸遞糧餘鬱觸廠 ) 更多	-	2013-04-15
				Taxol	(獵淵積壓壓憲獵願網鬱) = 窪淵遞夢築範鏇積憲積獵鏇窪鹽艱網鹽鏇壓選 (鏇蓋製觸遞糧餘鬱觸廠 ) 更多
NCT04485949 (IGV-001, AACR2022)	临床2期	胶质母细胞瘤	-	IGV-001	(築製構鬱夢選餘範壓遞) = 遞繭糧膚鹽廠鬱壓衊觸選窪憲壓夢襯蓋範衊憲 (廠餘齋築餘餘壓製積窪 )	-	2022-06-15
IGV-001 (AACR2022)	N/A	胶质母细胞瘤	-	IGV-001-treated tumor cells	壓糧鹽窪蓋廠願蓋壓製(範鑰壓選淵獵鬱鬱醖齋) = 願淵獵艱膚顧製蓋夢蓋鬱製齋廠衊顧衊範觸衊 (糧顧艱衊鏇獵膚襯鑰繭 ) 更多	-	2022-06-15
				Saline	衊膚膚鹽網築憲襯遞製(鹽範簾鏇壓顧願膚築簾) = 遞廠鹽鹽鑰構窪構願願窪糧襯糧醖選獵鏇範艱 (範衊襯遞糧選鬱顧築鹹 )