Delving into the Latest Updates on Furosemide/Digoxin with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Digoxin/furosemide, ICVT

Target

NKCC2

Mechanism

NKCC2 inhibitors(Sodium-(potassium)-chloride cotransporter 2 inhibitors)

Therapeutic Areas

NeoplasmsInfectious DiseasesSkin and Musculoskeletal Diseases+ [1]

Active Indication

Actinic KeratosisCondylomata AcuminataVulvar Neoplasms

Inactive Indication

Herpes SimplexKeratoconjunctivitis, InfectiousVulvar intraepithelial neoplasia

Originator Organization

Cutanea AS

Active Organization

Cutanea AS

Inactive Organization

Cutanea Life Sciences, Inc.Henderson Morley Plc

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC41H64O14

InChIKeyLTMHDMANZUZIPE-PUGKRICDSA-N

CAS Registry20830-75-5

View All Structures (2)

INTRODUCTIONActinic keratoses (AKs) are limited areas of irregular epidermal growth on a background of excessive solar exposure. The entire sun-damaged skin is considered a field of cancerization with multiple visible and subclinical lesions. AK management requires field-directed therapies to block lesion relapse and prevent squamous cell carcinoma (SCC).AREAS COVEREDIn this review, we focused on phase II clinical trials for AKs, involving well-known agents and newer molecules such as proapoptotic drugs (VDA-1102, SR-T100, oleogel-S10, ICVT, eflornithine), immunomodulants (isotretinoin, tretinoin) and chemopreventive agents (nicotinamide, perillyl alcohol, liposomal T4N5). We used the website 'ClinicalTrials.Gov' as main reference. We selected and discussed completed and ongoing trials and analysed chemical structure and mechanism of action of the investigated molecules.EXPERT OPINIONAK therapy should be tailored on the patient's profile considering first of all the age and site of the AKs, which are relevant parameters for local immune response. The new molecules could be combined to obtain a synergic effect blocking the different steps of skin tumorigenesis. Phase II trials highlight a new therapeutic opportunity to block selectively cell proliferation regulators and work both on the field of cancerization and on the AKs currently present.

01 May 2019·British Journal of DermatologyQ1 · MEDICINE

A randomized controlled proof‐of‐concept trial of digoxin and furosemide in adults with cutaneous warts

Q1 · MEDICINE

Article

Author: Kouwenhoven, S. ; Rijsbergen, M. ; Burggraaf, J. ; Feiss, G. ; Hogendoorn, G. ; de Koning, M. ; Lemoine, C. ; Rissmann, R. ; Klaassen, E.S. ; Niemeyer‐van der Kolk, T. ; Beck, S. ; Bouwes Bavinck, J.N.

BACKGROUNDTopical ionic contraviral therapy (ICVT) with digoxin and furosemide inhibits the potassium influx on which DNA viruses rely for replication. Therefore, ICVT was hypothesized to be a potential novel treatment for cutaneous warts.OBJECTIVESTo assess the clinical efficacy, safety and tolerability of ICVT in adults with cutaneous warts. The secondary objective was to gain insight into the underlying working mechanism of ICVT.METHODSTreatment with ICVT was assessed for efficacy, safety and tolerability in a single- centre, randomized, double-blind, placebo-controlled phase IIA trial. Eighty adult patients with at least two cutaneous warts (plantar or common) were randomized to one of four treatments: digoxin + furosemide (0·125%), digoxin (0·125%), furosemide (0·125%) or placebo. The gel was administered once daily for 42 consecutive days. Predefined statistical analysis was performed with a mixed-model ancova. The trial was registered at ClinicalTrials.gov with number NCT02333643.RESULTSWart size and human papillomavirus (HPV) load reduction was achieved in all active treatment groups. A statistically significant reduction in wart diameter of all treated warts was shown in the digoxin + furosemide treatment group vs. placebo (-3·0 mm, 95% confidence interval -4·9 to -1·1, P = 0·002). There was a statistically significant reduction in the HPV load of all treated warts in the digoxin + furosemide group vs. placebo (-94%, 95% confidence interval -100 to -19, P = 0·03). With wart size reduction, histologically and immunohistochemically defined viral characteristics disappeared from partial and total responding warts.CONCLUSIONSThis study demonstrates the proof of concept for the efficacy of topical ICVT in adults with cutaneous warts.

01 Dec 2017·Journal of the European Academy of Dermatology and Venereology

Topical ionic contra‐viral therapy comprised of digoxin and furosemide as a potential novel treatment approach for common warts

Article

Author: de Koning, M.N.C. ; Genders, R.E. ; Burggraaf, J. ; Klaassen, E.S. ; Rijneveld, R. ; Bouwes Bavinck, J. N. ; Dillingh, M.R. ; van der Kolk, T. ; Feiss, G. ; Kouwenhoven, S.T.P. ; Rissmann, R.

AbstractBackgroundDNA viruses such as HPV rely on K+ influx for replication. Both digoxin and furosemide inhibit the K+ influx by interacting with cell membrane ion co‐transporters (Na+/K+‐ATPase and Na+‐K+‐2Cl− co‐transporter‐1, respectively). We therefore hypothesized that these two compounds in a topical formulation may be valuable in the treatment of HPV‐induced warts. This new approach is called Ionic Contra‐Viral Therapy (ICVT).ObjectiveTo evaluate systemic exposure, safety and tolerability of ICVT with a combination of furosemide and digoxin after repeated topical application in subjects with common warts. Furthermore, we aimed to evaluate pharmacodynamics effects of ICVT.MethodsTwelve healthy subjects with at least four common warts on their hands were included in the study and treated with a fixed dose of 980 mg topical gel containing 0.125% (w/w) digoxin and 0.125% (w/w) furosemide for 7 consecutive days on their lower back to assess safety and systemic exposure. Two warts were treated with 10 mg each and two served as negative controls to obtain preliminary evidence of treatment effect.ResultsICVT was well tolerated topically, and there was no evidence of systemic exposure of digoxin or furosemide. There were no clinical relevant safety findings and no serious adverse events (SAEs). A rapid and statistically significant reduction in diameter, height and volume of the warts was already observed at day 14.ConclusionICVT was found to be safe for administration to humans and 7 days of active treatment showed a statistical significant wart reduction compared to untreated control lesions, clearly indicating pharmacological activity.

100 Deals associated with Furosemide/Digoxin

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Actinic Keratosis	Phase 2	-	Cutanea AS	-
Condylomata Acuminata	Phase 2	-	Cutanea AS	-
Vulvar Neoplasms	Phase 2	-	Cutanea AS	-
Actinic Keratosis	Preclinical	NL	Cutanea Life Sciences, Inc.	-
Condylomata Acuminata	Preclinical	NL	Cutanea Life Sciences, Inc.	-
Herpes Simplex	Preclinical	GB	Henderson Morley Plc	-
Human Papillomavirus Infection	Preclinical	GB	Henderson Morley Plc	-
Keratoconjunctivitis, Infectious	Preclinical	AT	-	-
Keratoconjunctivitis, Infectious	Preclinical	SK	-	-
Vulvar intraepithelial neoplasia	Preclinical	NL	Cutanea Life Sciences, Inc.	-