Delving into the Latest Updates on Ripasudil Hydrochloride Hydrate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Ripasudil, Ripasudil hydrochloride hydrate (JAN), Ripasudil hydrocholoride hydrate

+ [5]

Target

ROCK

Mechanism

ROCK inhibitors(Rho-associated kinases inhibitors)

Therapeutic Areas

Eye DiseasesCongenital DisordersOther Diseases

Active Indication

GlaucomaFuchs' Endothelial DystrophyCorneal Edema+ [1]

Inactive Indication-

Originator Organization

Kowa Co., Ltd.

Active Organization

Kowa Pharmaceuticals America, Inc.Kowa Research Institute, Inc.

Kowa Co., Ltd.

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

JP (26 Sep 2014),

Glaucoma

Regulation-

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Structure

Molecular FormulaC15H21ClFN3O3S

InChIKeyDRZAXKMMRYEBQP-IDMXKUIJSA-N

CAS Registry887375-67-9

View All Structures (2)

Author: Lin, Charles C ; Chamberlain, Winston ; Lietman, Thomas M ; Koo, Ellen H ; Li, Jennifer Y ; Jeng, Bennie H ; Srinivasan, Amrita ; Syed, Zeba A ; Arnold, Benjamin F ; Varnado, Nicole ; Rose-Nussbaumer, Jennifer ; Abdelrahman, Sarah ; Benetz, Beth Ann ; Gensheimer, William ; Lass, Jonathan ; Clover, Jameson

IntroductionIt remains uncertain whether Descemet membrane endothelial keratoplasty (DMEK) or Descemet stripping only (DSO) yields better outcomes in patients with symptomatic Fuchs endothelial corneal dystrophy (FECD). This paper presents the protocol for the Descemet Endothelial Thickness Comparison Trial II (DETECT II), a multicentre, outcome-masked, randomised, placebo-controlled, clinical trial comparing DMEK to DSO with ripasudil (DSO-R) for this patient population.Methods and analysisA total of 60 patients with endothelial dysfunction due to symptomatic FECD will be enrolled from seven participating sites in the USA. The patients will be randomly assigned in a 1:1 ratio to one of the following treatment groups: group 1—DMEK plus topical placebo and group 2—DSO plus topical ripasudil 0.4%. The enrolment period is 24 months. The primary outcome is best spectacle-corrected visual acuity at 12 months. Secondary outcomes include peripheral and central endothelial cell density, visual acuity, vision-related quality of life and Pentacam Scheimpflug tomography. Study outcomes will be analysed using mixed effects linear regression. Adverse events, including rebubble procedures, endothelial failure and graft rejection, will be documented and analysed using appropriate statistical methods. DETECT II aims to provide evidence on the comparative effectiveness of DMEK and DSO-R. The results of this trial will contribute to optimising the treatment of FECD, while also exploring the cost-effectiveness of these interventions. Dissemination of findings through peer-reviewed publications and national/international meetings will facilitate knowledge translation and guide clinical practice in the field of corneal transplantation.Ethics and disseminationA data and safety monitoring committee has been empanelled by the National Eye Institute. All study protocols will be subject to review and approval by WCG IRB as the single IRB of record. This study will comply with the National Institute of Health (NIH) Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. Data from the trial will be made available on reasonable request.Trial registration numberNCT05275972.

16 Sep 2024·Eye (London, England)

Ocular effects of Rho kinase (ROCK) inhibition: a systematic review.

Review

Author: Goss, Deborah ; Lin, Jonathan B ; Baldwin, George ; Harris, James M ; Margeta, Milica A

Topical therapies targeting Rho-associated protein kinase (ROCK) signalling, including netarsudil (Rhopressa®) and ripasudil (Glanatec®), have become widely adopted as part of standard clinical practice to lower intraocular pressure (IOP) in patients with ocular hypertension or glaucoma. Given the pleiotropic roles of ROCK signalling, ROCK inhibition has the potential to cause unintended ocular side effects beyond IOP lowering in other substructures of the eye, both beneficial and deleterious. Additional experience and observation of patients treated with this class of medications have uncovered both new side effects not reported in the initial clinical trials, as well as potential benefits that have inspired off-label uses and that have been the topic of numerous clinical studies, case series, case reports, and translational studies. Here, we performed a comprehensive systematic review and identified 170 studies describing ocular effects of ROCK inhibition. In addition to describing well-established ocular effects associated with inhibition of ROCK signalling, such as conjunctival hyperaemia, corneal verticillata, and reticular corneal epithelial oedema, we also highlight other effects, such as corneal haemorrhages, changes in corneal contour, anterior subcapsular opacities, contact dermatitis, punctal stenosis, and eyelid wound dehiscence, which have been described in case series and case reports. Finally, we evaluated studies describing potential novel applications of ROCK inhibition for treating disorders affecting the cornea, the retina, and the optic nerve, finding strong evidence in support of a beneficial effect of ROCK inhibitors on corneal oedema due to corneal endothelial cell dysfunction. The other potential applications require further research.

01 Sep 2024·Pesticide Biochemistry and Physiology

Pseudomonas thivervalensis K321, a promising and effective biocontrol agent for managing apple Valsa canker triggered by Valsa mali

Article

Author: Meng, Yangguang ; Huang, Lili ; Liu, Ronghao ; Xu, Liangsheng ; Yuan, Weiwei ; Li, Jin

Plant growth-promoting rhizobacteria (PGPR) have been reported to suppress various diseases as potential bioagents. It can inhibit disease occurrence through various means such as directly killing pathogens and inducing systemic plant resistance. In this study, a bacterium isolated from soil showed significant inhibition of Valsa mali. Morphological observations and phylogenetic analysis identified the strain as Pseudomonas thivervalensis, named K321. Plate confrontation assays demonstrated that K321 treatment severely damaged V. mali growth, with scanning electron microscopy (SEM) observations showing severe distortion of hyphae due to K321 treatment. In vitro twigs inoculation experiments indicated that K321 had good preventive and therapeutic effects against apple Valsa canker (AVC). Applying K321 on apples significantly enhanced the apple inducing systemic resistance (ISR), including induced expression of apple ISR-related genes and increased ISR-related enzyme activity. Additionally, applying K321 on apples can activate apple MAPK by enhancing the phosphorylation of MPK3 and MPK6. In addition, K321 can promote plant growth by solubilizing phosphate, producing siderophores, and producing 3-indole-acetic acid (IAA). Application of 0.2% K321 increased tomato plant height by 53.71%, while 0.1% K321 increased tomato fresh weight by 59.55%. Transcriptome analysis revealed that K321 can inhibit the growth of V. mali by disrupting the integrity of its cell membrane through inhibiting the metabolism of essential membrane components (fatty acids) and disrupting carbohydrate metabolism. In addition, transcriptome analysis also showed that K321 can enhance plant resistance to AVC by inducing ISR-related hormones and MAPK signaling, and application of K321 significantly induced the transcription of plant growth-related genes. In summary, an excellent biocontrol strain has been discovered that can prevent AVC by inducing apple ISR and directly killing V. mali. This study indicated the great potential of P. thivervalensis K321 for use as a biological agent for the control of AVC.

1

News (Medical) associated with Ripasudil Hydrochloride Hydrate

14 Dec 2022

·www.prnewswire.com

Capstone Announces FDA Approval and EU Authorization of Doxorubicin Hydrochloride Liposome Injection

ROSEMONT, Ill., Dec. 14, 2022 /PRNewswire/ -- Capstone Development Services Company LLC ("Capstone") announced today that it has received approval from the U.S. Food and Drug Administration (FDA), as well as authorization from the European Commission for doxorubicin hydrocholoride liposomal injection. Authorized as a treatment for multiple types of cancer, the product was developed by Capstone in partnership with a leading medical products company. Continue Reading Doxorubicin Hydrochloride Liposome Injection is indicated for treatment of ovarian cancer, acquired immune deficiency syndrome (AIDS)-related Kaposi's Sarcoma and multiple myeloma. It also is authorized in the EU for treatment of metastatic breast cancer. The product is an anthracycline topoisomerase inhibitor encapsulated in liposomes for intravenous use. These approvals are a testament to our team's expertise in complex formulations. - Dan Robins, Ph.D., president, Capston Tweet this The authorizations mark the 19th and 20thth regulatory approvals Capstone has gained for products developed since its founding in 2013. Capstone funded, developed and led the regulatory approval process of the product. After gaining approvals, it transferred ownership of the product to its medical products partner. Dan Robins, Ph.D., president, Capstone, said: "These approvals are a testament to our team's expertise in complex formulations. We are thrilled to have led the development and regulatory process to bring this important product to market on behalf of our global partner." For more details about doxorubicin hydrocholoride liposomal injection, including the boxed warning for cardiomyopathy and infusion-related reactions, see full prescribing information. Doxorubicin Hydrochloride Liposome Injection , USP Important Safety Information WARNING Doxorubicin hydrochloride liposomal infusion can cause myocardial damage, including acute left ventricular failure. The risk of cardiomyopathy was 11% when the cumulative anthracycline dose was between 450mg/m2 to 550mg/m2. Assess left ventricular cardiac function prior to initiation of doxorubicin hydrochloride liposomal infusion, during treatment, and after treatment. Serious, life-threatening, and fatal infusion-related reactions can occur. Acute infusion-related reaction occurred in 11% of patient with solid tumors. Withhold doxorubicin hydrochloride liposomal infusion for infusion-related reactions and resume at a reduced rate. Discontinue doxorubicin hydrochloride liposomal infusion for serious or life-threatening infusion-related reactions. About Capstone Capstone was founded in 2013 by Water Street Healthcare Partners, a strategic investor focused exclusively on health care. The company leads development, manages regulatory services and achieves timely approval of health care products through partnerships with global pharmaceutical and medical companies. To date, Capstone has developed and gained regulatory approvals on 20 products in the U.S., EU and Canada. The company supports its partners with bringing new and affordable health care products to market. For more information, visit capstonedevservices.com. SOURCE Capstone

Drug Approval

100 Deals associated with Ripasudil Hydrochloride Hydrate

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External Link

KEGG	Wiki	ATC	Drug Bank
D10463	Ripasudil Hydrochloride Hydrate	S01EX	DB13165

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Glaucoma	JP	Kowa Co., Ltd.	26 Sep 2014

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Fuchs' Endothelial Dystrophy	Phase 3	DE	Kowa Research Institute, Inc.	30 Mar 2023
Fuchs' Endothelial Dystrophy	Phase 3	US	Kowa Research Institute, Inc.	30 Mar 2023
Fuchs' Endothelial Dystrophy	Phase 3	DK	Kowa Research Institute, Inc.	30 Mar 2023
Fuchs' Endothelial Dystrophy	Phase 3	CA	Kowa Research Institute, Inc.	30 Mar 2023
Fuchs' Endothelial Dystrophy	Phase 3	ES	Kowa Research Institute, Inc.	30 Mar 2023
Fuchs' Endothelial Dystrophy	Phase 3	GB	Kowa Research Institute, Inc.	30 Mar 2023
Corneal Edema	Phase 3	US	Kowa Research Institute, Inc.	04 Aug 2022
Corneal Edema	Phase 3	PR	Kowa Research Institute, Inc.	04 Aug 2022
Ophthalmologic surgical procedures	Phase 3	US	Kowa Research Institute, Inc.	04 Aug 2022
Ophthalmologic surgical procedures	Phase 3	PR	Kowa Research Institute, Inc.	04 Aug 2022

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04250207 (CTgov)	Phase 2	Fuchs' Endothelial Dystrophy	65	K-321 Solution (K-321 QID)	fcarqokroc(grzrxigtlu) = zavjwjpzwp qwehtttsqh (clnvddgaey, vlergvzycq - somkygnlcp) View more	-	05 Nov 2024
				Placebo Solution+K-321 Solution (K-321 BID)	fcarqokroc(grzrxigtlu) = modmaqiota qwehtttsqh (clnvddgaey, jcxwdoumpe - prfmvbbxdq) View more
APAO2023	Not Applicable	Corneal Edema	-	Pseudophakic Corneal Edema patients prescribed with Ripasudil	ouyqrkoxpw(oenphtytdz) = All cases had diffused conjunctival congestion and itching in the eyes ddlndeqgsm (hlrhuoovvs ) View more	-	23 Feb 2023
				Ripasudil (Reticular Corneal Edema cases)
AAO2022	Not Applicable	Fuchs' Endothelial Dystrophy	23	Topical Ripasudil	kmwwzhxqzr(ztutoaempm) = dfyuohocvo nkvyekllbo (cebzdcwtqf )	-	29 Sep 2022
ARVO2022	Not Applicable	-	-	Ripasudil ophthalmic solution	(vvzdlajzzq) = lkkmgkpuec nkdcbhrsjx (wbugvckugm )	Negative	01 May 2022
				Balanced salt solution (BSS)	(vvzdlajzzq) = nupgzkqmmo nkdcbhrsjx (wbugvckugm )
AAO2021	Not Applicable	Fuchs' Endothelial Dystrophy	-	DMEK+ripasudil	aiwtvcmmzu(lpspayvuyp) = cyjxuyfwso smwvyjvohm (szhxggczhn ) View more	-	13 Nov 2021
				Ripasudil	aiwtvcmmzu(lpspayvuyp) = sbmsgdxczj smwvyjvohm (szhxggczhn ) View more
APAO2021	Not Applicable	-	-	Ripasudil (Ctrl group)	bekujflqnc(ezjvefhpvg) = djlmzdifhf mtrvjnixat (ifzynhdvna )	-	05 Sep 2021
				TGF-Î² group	bekujflqnc(ezjvefhpvg) = vmorrxqlhq mtrvjnixat (ifzynhdvna )
not available (ARVO2019)	Not Applicable	Glaucoma, Open-Angle	271	Ripasudil 0.4% eye drops	(tliehikbxb) = rsavohgoji cmfkddvugw (bxqzxicqei )	Positive	01 Jul 2019
ARVO2019	Not Applicable	-	-	Placebo	(wslmjuddhl) = dwquauaygh lwpabuvllo (rkvmraszoq ) View more	-	01 Jul 2019
				Ripasudil 0.04%	(wslmjuddhl) = nfwyypkrlx lwpabuvllo (rkvmraszoq ) View more
ARVO2018	Not Applicable	Hyperemia	20	Brimonidine	(joneehrsye) = ulbkuocplc yquojefywh (eysfvvuudk ) View more	-	01 Jul 2018
				Ripasudil	(joneehrsye) = rgndqbxgwc yquojefywh (eysfvvuudk ) View more
2018 ARVO Annual Meeting (ARVO2018)	Not Applicable	-	20	Placebo instillation	koszrnzdpp(plvxnstsnz) = tkyeqnbgvn vsqesjlvbz (fmnngnbxjq ) View more	Positive	01 Jul 2018
				0.04% Ripasudil instillation	koszrnzdpp(plvxnstsnz) = yzayevhujh vsqesjlvbz (fmnngnbxjq ) View more