Delving into the Latest Updates on AGN-211745 with Synapse

Overview

Basic Info

Drug Type

siRNA

Synonyms

AGN 211745, AGN-745, SIRNA 027

+ [1]

Target

VEGFR1

Mechanism

VEGFR1 antagonists(Vascular endothelial growth factor receptor 1 antagonists), RNA interference

Therapeutic Areas

Congenital DisordersEye Diseases

Active Indication-

Inactive Indication

Originator Organization

Merck Sharp & Dohme Corp.

Active Organization-

Inactive Organization

Sirna Therapeutics, Inc.Allergan Ltd. (Ireland)

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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The purpose of this study will be to assess the safety and tolerability and dose-limiting toxicity of a single intravitreal injection of Sirna-027 (AGN211745) and to assess the anatomical changes in the retina, changes in CNV, and changes in visual acuity. Escalation to the next dose cohort will be completed following minimum of 2 weeks follow-up. Patients will be monitored intensively for three months, and then followed-up for safety up to 24 months post-injection.

Start Date01 Nov 2004

Sponsor / Collaborator

Allergan Ltd. (Ireland)

[+1]

100 Clinical Results associated with AGN-211745

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100 Translational Medicine associated with AGN-211745

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100 Patents (Medical) associated with AGN-211745

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9

Literatures (Medical) associated with AGN-211745

01 Apr 2021·Experimental eye researchQ3 · MEDICINE

RNA therapeutics in ophthalmology - translation to clinical trials

Q3 · MEDICINE

Review

Author: Aristides D. Tagalakis ; Cynthia Yu-Wai-Man ; Konstantinos N. Kafetzis ; Aanchal Gupta

The use of RNA interference technology has proven to inhibit the expression of many target genes involved in the underlying pathogenesis of several diseases affecting various systems. First established in in vitro and later in animal studies, small interfering RNA (siRNA) and antisense oligonucleotide (ASO) therapeutics are now entering clinical trials with the potential of clinical translation to patients. Gene-silencing therapies have demonstrated promising responses in ocular disorders, predominantly due to the structure of the eye being a closed and compartmentalised organ. However, although the efficacy of such treatments has been observed in both preclinical studies and clinical trials, there are issues pertaining to the use of these drugs which require more extensive research with regards to the delivery and stability of siRNAs and ASOs. This would improve their use for long-term treatment regimens and alleviate the difficulties experienced by patients with ocular diseases. This review provides a detailed insight into the recent developments and clinical trials that have been conducted for several gene-silencing therapies, including ISTH0036, SYL040012, SYL1001, PF-04523655, Sirna-027, QR-110, QR-1123, QR-421a and IONIS-FB-L_RX in glaucoma, dry eye disease, age-related macular degeneration, diabetic macular oedema and various inherited retinal diseases. Our aim is to explore the potential of these drugs whilst evaluating their associated advantages and disadvantages, and to discuss the future translation of RNA therapeutics in ophthalmology.

01 Feb 2021·Fundamental & clinical pharmacologyQ3 · MEDICINE

Progress on ocular siRNA gene‐silencing therapy and drug delivery systems

Q3 · MEDICINE

Review

Author: Li, Shuhan ; Tang, Yue ; Chen, Jing ; Zhang, Xinru ; Jiang, Jinjin

Abstract:

Age‐related macular degeneration (AMD) and glaucoma are global ocular diseases with high blindness rate. RNA interference (RNAi) is being increasingly used in the treatment of these disorders with siRNA drugs, bevasiranib, AGN211745 and PF‐04523655 for AMD, and SYL040012 and QPI‐1007 for glaucoma. Administration routes and vectors of gene drugs affect their therapeutic effect. Compared with the non‐viral vectors, viral vectors have limited payload capacity and potential immunogenicity. This review summarizes the progress of the ocular siRNA gene‐silencing therapy by focusing on siRNA drugs for AMD and glaucoma already used in clinical research, the main routes of drug delivery and the non‐viral vectors for siRNA drugs.

01 Jul 2010·American journal of ophthalmologyQ2 · MEDICINE

RNAi-Based Treatment for Neovascular Age-Related Macular Degeneration by Sirna-027

Q2 · MEDICINE

Article

Author: Quan Dong Nguyen ; Syed Mahmood Shah ; R.C. Andrew Symons ; Gail Reisen ; Homayoun Tabandeh ; Roberto Guerciolini ; Brian Short ; Edward J. Quinlan ; Diana V. Do ; Peter K. Kaiser ; Jennifer A. Lockridge

PURPOSE:

To assess the safety, tolerability, pharmacokinetics, and dose-limiting toxicity of single intravitreal injection of Sirna-027, a small interfering RNA targeting vascular endothelial growth factor receptor-1, in patients with choroidal neovascularization (CNV) resulting from neovascular age-related macular degeneration (AMD). Secondary objectives included assessment of anatomic changes in retinal thickness, size of CNV, and changes in visual acuity.

DESIGN:

Prospective, open-label, single-dose, dose-escalation phase 1 study.

METHODS:

Twenty-six eyes of 26 patients with a median age of 82 years and CNV resulting from AMD who had previous treatments with other therapies were treated at 2 academic retinal practices. Patients received a single dose of Sirna-027 (100, 200, 400, 800, 1200, or 1600 microg/eye). Blood was sampled for pharmacokinetic analysis at 1, 4, and 24 hours after injection and on day 7. Patients underwent ophthalmic examinations including visual acuity, fluorescein angiography, and optical coherence tomography at screening and days 7, 14, 28, and 84. The main outcome measures were adverse reactions and dose-limiting toxicities.

RESULTS:

Intravitreal injection of a single dose of Sirna-027 from 100 to 1600 microg was well tolerated in patients with AMD, with no dose-limiting toxicity found. Adverse events were mild to moderate in severity. Adjusted mean foveal thickness decreased within 2 weeks after study treatment. The decrease was most pronounced in the 100- and 200-microg doses.

CONCLUSIONS:

A single intravitreal dose of Sirna-027 up to 1600 microg/eye was well tolerated in patients with CNV resulting from neovascular AMD that had been refractory to other therapies. Stabilization or improvement in visual acuity and foveal thickness was observed. No dose-response or dose-limiting effects were noted.

100 Deals associated with AGN-211745

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB05896

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Age Related Macular Degeneration	Phase 2	US	Sirna Therapeutics, Inc.	01 Nov 2004
Age Related Macular Degeneration	Phase 2	US	Allergan Ltd. (Ireland)	01 Nov 2004
Choroidal Neovascularization	Phase 2	US	Sirna Therapeutics, Inc.	01 Nov 2004
Choroidal Neovascularization	Phase 2	US	Allergan Ltd. (Ireland)	01 Nov 2004
Dystrophy, Macular	Phase 2	US	Allergan Ltd. (Ireland)	01 Nov 2004

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00395057 (CTgov)	Phase 2	Choroidal Neovascularization \| Age Related Macular Degeneration	138	AGN 211745 (AGN 211745 Solution 1000 ug)	xfkfjwexja(edytllmzzw) = qfjuxrksal zycfvqcgyj (ictwmmgjmz, sjrhitgvun - lyinztaken) View more	-	13 Dec 2011
				AGN 211745 (AGN 211745 Solution 300 ug)	xfkfjwexja(edytllmzzw) = pdjrnnkfml zycfvqcgyj (ictwmmgjmz, wsfzdtpdhq - ngracmzian) View more