Delving into the Latest Updates on Alfimeprase(Amgen, Inc.) with Synapse

Overview

Basic Info

Drug Type

Enzyme

Synonyms

Alfimeprase, Alfimeprase (USAN/INN)

Target

Fibrinogen

Mechanism

Fibrinogen modulators

Therapeutic Areas

Cardiovascular DiseasesNervous System Diseases

Active Indication-

Inactive Indication

Acute Ischemic StrokeArterial Occlusive DiseasesCatheter related thrombosis+ [5]

Originator Organization

Amgen, Inc.

Active Organization-

Inactive Organization

ARCA biopharma, Inc.

Amgen, Inc.

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

Regulation-

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Gene Sequence

Sequence Code 18530

Source: *****

BACKGROUNDAn optimal strategy to improve reperfusion in patients with arterial occlusions is a recognized clinical need. We hypothesized that hirudin (thrombin inhibitor) and S18886 [S18, thromboxane A(2) receptor (TP) antagonist] would improve blood flow and reperfusion rates after thrombolysis with the direct-acting fibrinolytic enzyme alfimeprase.METHODSIn anesthetized beagles, carotid artery thrombosis was induced by electrolytic endothelial injury. After 30 minutes of occlusion, animals were administered vehicle, hirudin, and/or S18. Carotid artery blood flow was monitored for 90 minutes after the infusion of alfimeprase or recombinant tissue plasminogen activator (rt-PA).RESULTSThe onset to reperfusion was more rapid in animals treated with alfimeprase than in those treated with rt-PA. All the animals treated with hirudin + S18 + alfimeprase maintained vessel patency, and all vehicle-treated animals reoccluded. In animals treated with hirudin + S18 + alfimeprase, time to reocclusion and total reflow time after thrombolysis were longer compared with vehicle-treated animals. The quality and quantity of blood flow were most improved in animals treated with hirudin + S18 + alfimeprase. There were no significant differences in time to reocclusion, total reflow time, and quality and quantity of blood flow between vehicle + rt-PA-treated animals and hirudin + S18 + rt-PA-treated animals.CONCLUSIONSDual antithrombotic therapy with hirudin and S18 improves reperfusion after thrombolysis with alfimeprase but not rt-PA.

01 May 2012·HaematologicaQ1 · MEDICINE

Thrombolytic therapy for central venous catheter occlusion

Q1 · MEDICINE

Review

Author: Jacquelyn L. Baskin ; Monika L. Metzger ; Judith A. Wilimas ; Scott C. Howard ; Raul C. Ribeiro ; Ching-Hon Pui ; Ulrike Reiss

BACKGROUNDLong-term central venous catheters have improved the quality of care for patients with chronic illnesses, but are complicated by obstructions which can result in delay of treatment or catheter removal.DESIGN AND METHODSThis paper reviews thrombolytic treatment for catheter obstruction. Literature from Medline searches using the terms "central venous catheter", "central venous access device" OR "central venous line" associated with the terms "obstruction", "occlusion" OR "thrombolytic" was reviewed. Efficacy of thrombolytic therapy, central venous catheter clearance rates and time to clearance were assessed.RESULTSAlteplase, one of the current therapies, clears 52% of obstructed catheters within 30 min with 86% overall clearance (after 2 doses, when necessary). However, newer medications may have higher efficacy or shorter time to clearance. Reteplase cleared 67-74% within 30-40 min and 95% of catheters overall. Occlusions were resolved in 70 and 83% of patients with one and 2 doses of tenecteplase, respectively. Recombinant urokinase cleared 60% of catheters at 30 min and 73% overall. Alfimeprase demonstrated rapid catheter clearance with resolution in 40% of subjects within 5 min, 60% within 30 min, and 80% within 2 h. Additionally, urokinase prophylaxis decreased the incidence of catheter occlusions from 16-68% in the control group to 4-23% in the treatment group; in some studies, rates of catheter infections were also decreased in the urokinase group.CONCLUSIONSThrombolytic agents successfully clear central venous catheter occlusions in most cases. Newer agents may act more rapidly and effectively than currently utilized therapies, but randomized studies with direct comparisons of these agents are needed to determine optimal management for catheter obstruction.

01 Mar 2010·Journal of Thrombosis and HaemostasisQ2 · MEDICINE

Direct fibrinolytic agents: biochemical attributes, preclinical foundation and clinical potential

Q2 · MEDICINE

Review

Author: V. Novokhatny ; V. J. Marder

Direct fibrinolytics are proteolytic enzymes that degrade fibrin without requiring an intermediate step of plasminogen activation. This review summarizes the current information available for five such agents, namely, plasmin (the prototypical form), three derivatives of plasmin (mini-plasmin, micro-plasmin, and delta-plasmin), and alfimeprase, a recombinant variant of a snake venom alpha-fibrinogenase, fibrolase. Biochemical attributes of molecular size, fibrin binding and inhibitor neutralization are compared. Preclinical investigations that assess the potential for thrombolytic efficacy in vitro and in animal models of vascular occlusion and for hemostatic safety in animal models of bleeding are detailed. Clinical potential has been assessed in patients with peripheral arterial and graft occlusion, acute ischemic stroke, and access catheter and hemodialysis shunt occlusions. The direct fibrinolytic agents have impressive biochemical and preclinical foundations for ultimate clinical application. However, clinical trial results for micro-plasmin and alfimeprase have not measured up to their anticipated benefit. Plasmin has thus far shown encouraging hemostatic safety, but efficacy data await completion of clinical trials. Whether direct fibrinolytics will provide clinical superiority in major thrombotic disorders over currently utilized indirect fibrinolytics such as tissue plasminogen activator remains to be determined.

100 Deals associated with Alfimeprase(Amgen, Inc.)

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External Link

KEGG	Wiki	ATC	Drug Bank
D08848	-	-	DB04919

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Ischemic Stroke	Phase 3	US	ARCA biopharma, Inc.	01 Jun 2007
Acute Ischemic Stroke	Phase 3	CA	ARCA biopharma, Inc.	01 Jun 2007
Catheter related thrombosis	Phase 3	US	ARCA biopharma, Inc.	01 Jan 2006
Venous Thrombosis	Phase 3	US	ARCA biopharma, Inc.	01 Sep 2005
Arterial Occlusive Diseases	Phase 3	US	ARCA biopharma, Inc.	01 Apr 2005
Occlusion of artery	Phase 3	US	ARCA biopharma, Inc.	01 Apr 2005
Peripheral Vascular Diseases	Phase 3	US	ARCA biopharma, Inc.	01 Jun 2003
Peripheral Arterial Occlusive Disease 1	Phase 3	-	Amgen, Inc.	-
Thrombosis	Phase 3	-	Amgen, Inc.	-