Delving into the Latest Updates on PF-4523655 with Synapse

Overview

Basic Info

Drug Type

siRNA

Synonyms

+ [5]

Target

Redd1

Mechanism

Redd1 inhibitors(DNA damage-inducible transcript 4 protein inhibitors), RNA interference

Therapeutic Areas

Cardiovascular DiseasesCongenital DisordersEndocrinology and Metabolic Disease+ [1]

Active Indication

Diabetic macular oedemaDystrophy, Macular

Inactive Indication

Originator Organization

Silence Therapeutics Plc

Active Organization

Silence Therapeutics Plc

Inactive Organization

Pfizer Inc.

Quark Pharmaceuticals, Inc.

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure/Sequence

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Sequence Code 29674253Sense strand

Sequence Code 29646826Antisense strand

An Open-Label Dose Escalation Study of PF-04523655 (Stratum I) Combined With a Prospective, Randomized, Double-Masked, Multi-Center, Controlled Study (Stratum II) Evaluating the Efficacy and Safety of PF-04523655 Alone and in Combination With Ranibizumab Versus Ranibizumab Alone in Diabetic Macular Edema (MATISSE STUDY)

This is a two-part study. The first part (Stratum I) is an open-label, dose escalation, safety, tolerability and pharmacokinetic study, where active study drug (PF-04523655) will be given to all patients who participate. Stratum I will determine the maximum tolerated dose and any dose-limiting toxicities. The second part (Stratum II) is a prospectively randomized, multi-center, double-masked, dose ranging study evaluating the efficacy and safety of PF-04523655 alone and in combination with ranibizumab versus ranibizumab alone in patients with DME.

Start Date01 Feb 2012

Sponsor / Collaborator

Quark Pharmaceuticals, Inc.

NCT00713518

/ CompletedPhase 2

Phase II Open Label Multicenter, Prospective, Randomized, Age Related Macular Degeneration, Comparator Controlled Study Evaluating PF-04523655 Versus Ranibizumab In The Treatment Of Subjects With Choroidal Neovascularization (MONET Study).

The aim of the study is to evaluate whether PF-04523655 is effective in the treatment of neovascular/wet AMD and at which dose.

Start Date01 Nov 2009

Sponsor / Collaborator

Quark Pharmaceuticals, Inc.

[+1]

EUCTR2008-003210-10-AT

/ Not yet recruitingNot Applicable

PHASE II OPEN LABEL, MULTICENTER, PROSPECTIVE,RELATED MACULAR DEGENERATION, COMPARATOR STUDY EVALUATING PF-04523655 VERSUS RANIBIZUMAB TREATMENT OF SUBJECTS WITH CHOROIDAL NEOVASCULARIZATION (MONET STUDY)

Start Date24 Sep 2009

Sponsor / Collaborator

Pfizer Inc.

100 Clinical Results associated with PF-4523655

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100 Translational Medicine associated with PF-4523655

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100 Patents (Medical) associated with PF-4523655

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9

Literatures (Medical) associated with PF-4523655

01 Apr 2021·Experimental Eye ResearchQ3 · MEDICINE

RNA therapeutics in ophthalmology - translation to clinical trials

Q3 · MEDICINE

Review

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

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

AbstractAge‐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.

23 Dec 2019·Journal of OphthalmologyQ4 · MEDICINE

Clinical Role of Epigenetics and Network Analysis in Eye Diseases: A Translational Science Review

Q4 · MEDICINE

ReviewOA

Author: Benincasa, Giuditta ; Napoli, Claudio ; Costa, Dario ; Lanza, Michele

Network medicine is a molecular-bioinformatic approach analyzing gene-gene interactions that can perturb the human interactome. This review focuses on epigenetic changes involved in several ocular diseases, such as DNA methylation, histone and nonhistone post-translational modifications, and noncoding RNA regulators. Although changes in aberrant DNA methylation play a major role in the pathogenesis of most ocular diseases, histone modifications are seldom investigated. Hypermethylation in TGM-2 and hypomethylation in MMP-2/CD24 promoter genes may play a crucial role in pterygium development; hypermethylation in regulatory regions of GSTP1 and OGG1 genes appear to be diagnostic biomarkers of cataract; hypomethylation of TGF-β1 promoter may trigger glaucoma onset; hypermethylation of the LOXL1 gene might be associated with pseudoexfoliation syndrome. A large panel of upregulated micro-RNAs (miRNAs), including hsa-hsa-miR-494, hsa-let-7e, hsa-miR-513-1, hsa-miR-513-2, hsa-miR-518c, hsa-miR-129-1, hsa-miR-129-2, hsa-miR-198, hsa-miR-492, hsa-miR-498, hsa-miR-320, hsa-miR-503, and hsa-miR-373,∗ may have a putative role in the development of retinoblastoma. Hypermethylation of H3K4 and hypomethylation of H3K27 at the TGFBIp locus are putative pathogenic mechanisms involved in corneal dystrophies. Determining how, where, and when specific epigenetic changes trigger ocular diseases may provide useful clinical biomarkers for their prevention, diagnosis, and management, as well as innovative drug targets. PF-04523655, a 19-nucleotide methylated double-stranded siRNA targeting the RTP80 gene, showed a dose-related improvement in best-corrected visual acuity (BCVA) in patients affected by diabetic macular edema. The observed results support a clinical network-based research program aimed to clarify the role of epigenetic regulators in the development of ocular diseases and personalized therapy.

100 Deals associated with PF-4523655

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetic macular oedema	Phase 2	-	Silence Therapeutics Plc	-
Dystrophy, Macular	Phase 2	-	Silence Therapeutics Plc	-
Choroidal Neovascularization	Preclinical	TR	Pfizer Inc.	01 Nov 2009
Choroidal Neovascularization	Preclinical	HK	Quark Pharmaceuticals, Inc.	01 Nov 2009
Choroidal Neovascularization	Preclinical	IN	Pfizer Inc.	01 Nov 2009
Choroidal Neovascularization	Preclinical	PH	Quark Pharmaceuticals, Inc.	01 Nov 2009
Choroidal Neovascularization	Preclinical	AT	Quark Pharmaceuticals, Inc.	01 Nov 2009
Choroidal Neovascularization	Preclinical	DK	Pfizer Inc.	01 Nov 2009
Choroidal Neovascularization	Preclinical	HK	Pfizer Inc.	01 Nov 2009
Choroidal Neovascularization	Preclinical	US	Pfizer Inc.	01 Nov 2009

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00725686 (ARVO2009)	Phase 1	Wet age-related macular degeneration	13	PF-04523655	(ndhtvbvzex) = amojtjoutq pwnirjpqgy (ojlnspasqv, +12.25) View more	-	01 Apr 2009