Delving into the Latest Updates on Sulodexide with Synapse

Retinal vascular diseases, such as diabetic retinopathy or retinal vein occlusion, are common causes of severe vision loss. Central to the pathophysiology of these conditions are endothelial dysfunction, inflammation, capillary leakage, ischemia, and pathological neoangiogenesis. Capillary damage leads to leakage and the development of macular edema, which is associated with vision loss and requires complex treatment. Sulodexide, a glycosaminoglycan composed of heparan sulfate and dermatan sulfate with high oral bioavailability, exhibits several favorable pharmacologic properties, including antithrombotic, anti-inflammatory, and endothelium-protective effects. Additionally, treatment with sulodexide has been associated with the reduction of oxidative stress and decreased expression of angiogenic growth factors, such as vascular endothelial growth factor. This review aims to provide an overview of the pharmacological properties, mechanisms of action, and therapeutic effects of sulodexide. Furthermore, its potential for clinical application in venous and diabetic diseases, such as venous thromboembolism, chronic venous insufficiency, peripheral artery disease, or diabetic nephropathy, is summarized. We also present experimental and clinical studies evaluating the potential of sulodexide in ocular conditions and discuss its therapeutic implications for the treatment of retinal vascular diseases.

01 Mar 2025·Journal of Vascular Surgery-Venous and Lymphatic Disorders

UTILITY OF VENOACTIVE COMPOUNDS IN POST-THROMBOTIC SYNDROME: A SYSTEMATIC REVIEW

Review

Author: Raffetto, Joseph D ; Gloviczki, Peter ; Puggioni, Alessandra ; Stoughton, Julianne ; Gloviczki, Monika L

BACKGROUND:

Post-thrombotic syndrome (PTS) has been highly prevalent; over 50% of the patients develop PTS after lower extremity acute deep vein thrombosis. Venoactive compounds (VACs) have been recommended for decades for patients with chronic venous insufficiency, including PTS. The objective of our study was to perform a systematic review to determine the quality of evidence on the utility of VACs for both prevention and treatment of PTS.

METHODS:

A systematic review was conducted to search the literature between January 1, 1980, and July 14, 2023, for venoactive drugs or medications, deep vein thrombosis, and PTS using PubMed, MEDLINE, life science journals, and the Cochrane Library. Only randomized controlled trials (RCTs) published in English were included in this review. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the revised Cochrane risk-of-bias tool for RCTs were used.

RESULTS:

Ninety-four references were identified; 11 RCTs fulfilled the inclusion criteria. VACs administered were diosmin, hidrosmin/rutosides, micronized purified flavonoid fraction (MPFF), and sulodexide. The studies included a highly variable proportion of patients with PTS (8.6%-100%). Some older studies omitted details of the methodology. Two studies suggested benefit of diosmin and MPFF as adjunctive treatment to rivaroxaban in the prevention of PTS and showed low or unclear risk of bias. Evaluation of RCTs for the treatment of post-thrombotic chronic venous insufficiency found low or unclear risk of bias in 81.6% to 85.7%. All studies suggested that VACs were beneficial for PTS treatment; they improved venous symptoms, decreased edema, and helped heal venous ulcers.

CONCLUSIONS:

This systematic review found that VACs had at least moderate quality of evidence in improving venous symptoms, decreasing edema, and accelerating venous ulcer healing. Two pilot RCTs of higher quality suggested the usefulness of diosmin and MPFF as adjunctive treatment to rivaroxaban therapy to reduce the incidence of PTS and improve deep vein recanalization. Because most RCTs were published over two decades ago, and several lacked the required precision in reporting, new high-quality, low-bias RCTs are needed to assess the role of specific VACs for both prevention and treatment of PTS.

01 Feb 2025·CLINICAL HEMORHEOLOGY AND MICROCIRCULATION

The modulation of endothelial glycocalyx by sulodexide on the porcine model of enzymatic endothelial glycocalyx damage – a pilot study

Article

Author: Motesicky, Jan ; Cerny, Vladimir ; Hyspler, Radomir ; Navratil, Pavel ; Zadak, Zdenek ; Lehmann, Christian ; Malbrain, Manu LNG ; Ssali, Edward ; Zrzavecky, Marek ; Kawashima, Hanako ; Ticha, Alena ; Hana, Ludek ; Astapenko, David ; Radochova, Vera ; Gorskaja, Diana

Background:

Sulodexide is a glycosaminoglycan-based drug prescribed to patients with angiopathy. We performed a pilot study to investigate whether sulodexide positively modulates the endothelial glycocalyx (EG) layer and the microcirculation in a porcine model of EG enzymatic damage. The EG is a sugar-based endothelial lining that is involved in the physiology of the capillary wall and the pathogenesis of many diseases.

Methods:

EG damage was induced in eight piglets by hyaluronidase III and heparanase I given intravenously. Four animals received sulodexide 600 IU intravenously before the enzymes and four animals after the enzymes were administered. Four animals constituted a control group. Sublingual microcirculation by side-stream dark field imaging and plasmatic concentration of syndecan-1 by ELISA were measured at baseline, 20 min after intervention, and at the 40th, and 60th minute onwards. The statistics were performed with a one-way ANOVA test with Turkey's correction for multiple comparisons testing. Timepoint comparison was performed by Student t-test or Mann-Whitney test.

Results:

At baseline, there were no statistically significant differences between the animal groups. After the intervention, the levels of syndecan-1 were significantly lower in the control group. While there were no differences between the two intervention groups. The sublingual microcirculation analysis showed that the DeBacker score was significantly higher in the control group. At 60 min, there was also a statistically significant difference in DeBacker score between the groups (8.1 ± 1.6 mm −1 in the group with enzymes given first and 11 ± 0.92 mm −1 in the group with sulodexide given first, p = 0.03). The analysis of the proportion of perused vessels did not show any statistically significant differences.

Conclusion:

The results of the study demonstrated a working model of EG damage but no specific action of sulodexide on EG modulation. In the sublingual microcirculation analysis, the sulodexide reduced the fall in absolute tissue perfusion in 60 min.

1

News (Medical) associated with Sulodexide

26 Sep 2023

·www.biopharmadive.com

Intercept, after biotech rollercoaster ride, agrees to buyout by Alfasigma

Liver drug developer Intercept Pharmaceuticals has agreed to be acquired by Italian company Alfasigma for about $800 million, the companies announced Tuesday, ending one of biotechnologys most noteworthy stories of investor exuberance and clinical disappointment in the last decade.Alfasigma will pay Intercept investors $19 per share in cash, an 82% premium from Intercepts closing price on Monday. Alfasigma will fund the transaction with cash on hand and corporate credit facilities, and expects to close the deal by the end of 2023.With the acquisition, Alfasigma will gain Ocaliva, a drug that treats the rare autoimmune disorder primary biliary cholangitis, or PBC, which had sales of $152 million in the first six months of the year. The company recorded losses of $38 million over the same period.Alfasigma executives said the transaction will help it develop its U.S. presence. Intercept represents a compelling fit with Alfasigmas core business areas of gastroenterology and hepatology, and we believe that the transaction represents a transformational opportunity for both companies, said Alfasigma CEO Francesco Balestrieri in a statement.A closely held company controlled by the family of its founder, Alfasigma markets drugs like Zelnorm and rifaximin for irritable bowel syndrome and sulodexide for post-thrombotic syndrome. It also provides contract manufacturing services, as well as nutritional supplements. Its factory in Shreveport, Louisiana,manufactures nutritional supplements for the U.S. market.While Ocalivafirst gained approval for PBC, the drugs potential in the liver disease NASH drove investor enthusiasm in Intercept. NASH, or non-alcoholic steatohepatitis, is a disease connected with obesity, and its believed to be growing widely in prevalence.In 2014, a National Institutes of Health Phase 2 study of Ocaliva in people with NASH was stopped early because it had met its primary goal improvement in disease activity score at an interim analysis. Shares in the company nearly quadrupled in value and took the companys valuation to more than $7 billion, sparking an investor rush to find other companies working on NASH drugs.The path to regulators was not straightforward, however. Intercept reported positive Phase 3 data in 2019, but the FDA asked for longer-term data,rejectingIntercepts first NASH application.The FDA turned back a second application earlier this year, as Ocalivas only modest benefit was balanced against signs of liver damage experienced by some trial participants given the drug. Following that rejection, Intercept canceled all work in NASH, claiming it wasnt economically feasible to collect the data asked for by the FDA, and laid off staff.Meanwhile, competition in Intercepts established market of PBC may be emerging, as CymaBays seladelpar and Genfits elafibranor near key milestones.Raymond James analyst Steven Seedhouse described the transaction as a great return for Intercept investors.Given our bullish view of seladelpar and its ability to take market share in PBC beginning as early as late 2024, it isnt clear to us if [Ocaliva] will even generate that much net profit in the next ~10 years, Seedhouse wrote in a note to clients. '

Clinical ResultAcquisitionPhase 2Drug ApprovalPhase 3

100 Deals associated with Sulodexide

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KEGG	Wiki	ATC	Drug Bank
D08547	Sulodexide	B01AB11	DB06271

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Atherosclerosis	China	Alfa Wassermann SpA	15 Aug 2003
Diabetes Complications	China	Alfa Wassermann SpA	15 Aug 2003
Thrombosis	China	Alfa Wassermann SpA	15 Aug 2003

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Endothelial dysfunction	Phase 3	Mexico	Alfasigma SpA	01 Jun 2023
Post Acute COVID 19 Syndrome	Phase 3	Mexico	Alfasigma SpA	01 Jun 2023
Chronic venous insufficiency	Phase 3	Czechia	Alfasigma SpA	25 Nov 2021
Vein disorder	Phase 3	Czechia	Alfasigma SpA	25 Nov 2021
Arterial Occlusive Diseases	Phase 3	Tunisia	Alfa Wassermann, Inc.	31 Jan 2019
Peripheral arterial occlusive disease	Phase 3	Tunisia	Alfa Wassermann, Inc.	31 Jan 2019
Venous Insufficiency	Phase 3	Poland	Alfa Wassermann SpA	03 Sep 2016
Chronic Kidney Diseases	Phase 3	Philippines	Alfasigma SpA	01 Nov 2009
Type 2 diabetes mellitus with established diabetic nephropathy	Phase 3	Australia	Keryx Biopharmaceuticals, Inc.	01 Apr 2007
Diabetes Mellitus, Type 2	Phase 3	United States	Keryx Biopharmaceuticals, Inc.	01 Aug 2005

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


Code Large Vessel Occlusion Process (ISC2024)	Not Applicable	occlusions RACE score ≥ 5 \| aphasia \| visual field cut ... View more	-	Code Large Vessel Occlusion Process (MER with code LVO activation)	jjwfxxzfrr(fhmdufdmip) = zvxrbelgkj bqjcwlmlnr (zakjrrtlca ) View more	Negative	01 Feb 2024
AUA2021	Not Applicable	Complication	-	Bipolar vessel sealing system	vsxbgwoyxp(oqjecduftc) = wiimrwxhvv anynpascdq (qmisbuctue ) View more	-	01 Sep 2021
				BIPOLAR VESSEL SEALING SYSTEM (Silk ligation)	vsxbgwoyxp(oqjecduftc) = ivmugadmsw anynpascdq (qmisbuctue ) View more
ISTH2020	Not Applicable	-	-	Sulodexide	ttcqdhprve(ygzlortfes) = qegaphqfdn qnjjlyoehn (qzrpjulhcw )	-	12 Jul 2020
				Porcine Heparin	ttcqdhprve(ygzlortfes) = xrygeabetu qnjjlyoehn (qzrpjulhcw )
ISTH2020	Not Applicable	-	-	Parenteral Sulodexide	znhazstvxk(izuduswzse) = vohufyiyry izlqiodhiw (mkxzqvqrvi )	-	12 Jul 2020
				Saline	znhazstvxk(izuduswzse) = ewcfnjxump izlqiodhiw (mkxzqvqrvi )
NCT00130208 (CTgov)	Phase 3	Diabetes Mellitus, Type 2 \| Diabetic Nephropathies	1,056	Sulodexide (Sulodexide)	cwlcaibeuw = nhcbmdtlce trepcxugdd (hrffpostjp, gwhjyemayy - pqxdsfdkhf) View more	-	23 Mar 2018
				Placebo (Placebo)	cwlcaibeuw = jbfvusogyz trepcxugdd (hrffpostjp, jhmxuvunrv - prdixsbfpa) View more
Sun-MACRO (ASN2015)	Not Applicable	Albuminuria urinary albumin-creatinine ratio (UACR)	843	Sulodexide 200 mg/d	haesljgmfy(wrvcqkobky) = qeumazvyys itqinykkqk (wpxozprbbn, ±0.9)	Positive	03 Nov 2015
				Placebo	haesljgmfy(wrvcqkobky) = sllncjbhpn itqinykkqk (wpxozprbbn, ±0.9)
NCT01295775 (DRESS, Pubmed \| Graefes Arch Clin Exp Ophthalmol)	Phase 2	Nonproliferative diabetic retinopathy	130	Sulodexide	vqxxrlwypu(eiocsthdgm) = lsjwvmhfhf dtiizmqlgb (eaccuazejy )	Positive	01 Jun 2015
				Placebo	vqxxrlwypu(eiocsthdgm) = yhekdlepyz dtiizmqlgb (eaccuazejy )
[PP.35.20] (ESH2015)	Not Applicable	Hypotension	-	Sulodexide	uzadoquety(irxaatqknj) = sneebmvttn dmulizlotm (udkaxhufno, 0.6–2.9) View more	Positive	01 Jun 2015
FP585 (ERA2015)	Not Applicable	-	6	Sulodexide	asnsnbfqkw(onzldjqtqc) = ztogkxumvp pupturvwgk (bscqvecewk )	Positive	21 May 2015
ASN2014	Not Applicable	-	-	Sulodexide treatment	zmdgpkioda(wlzmtrrqcn) = vndluusjpx znxbacohoe (spjrfzceqb, -3.9 to -0.8) View more	Positive	11 Nov 2014