Boehringer Ingelheim Gets First Approval Within EU For Actilyse(R) 2mg To Treat Catheter Dysfunction Caused By Thrombotic Occlusion

Main Category: Blood / Hematology
Also Included In: Regulatory Affairs / Drug Approvals;  Urology / Nephrology
Article Date: 02 Jun 2008 - 5:00 PDT

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Boehringer Ingelheim announced the first approval for Actilyse® (alteplase) 2mg within the European Union, which was communicated by the reference member state Germany after successful completion of a mutual recognition procedure. The new indication is for the thrombolytic treatment of occluded central venous access devices (CVAD), including those used for haemodialysis. This regulatory milestone will result in subsequent approvals of the new indication in the relevant countries of the European Union throughout 2008 onwards. Actilyse® is already registered in more than 85 countries across the world for the indications acute myocardial infarction, acute massive pulmonary embolism, and acute ischaemic stroke.

A dose of up to 2mg of Actilyse® (alteplase) administered up to two times into the occluded central venous access device, can restore function of catheters, including those used for haemodialysis, which become dysfunctional due to thrombotic occlusion.2 Actilyse® 2mg works by activating plasminogen, which dissolves fibrin (a substance that causes blood to clot), breaking down the thrombus and restoring function to the CVAD.

Catheter dysfunction may be caused by a variety of conditions, such as catheter malposition, mechanical failure, constriction by a suture, lipid deposits or drug precipitates within the catheter lumen and importantly by thrombus formation.

"Until now, there have been limited treatment options available in Europe to healthcare professionals to restore catheter function following thrombotic occlusion. In many cases, the only option has been to remove and replace the catheter. Therefore, the approval of this new indication for alteplase is welcome news for physicians and for the many patients who rely on central venous access devices for their medical care," said Dr. Andreas Barner, Member of the Board of Boehringer Ingelheim and responsible for Research, Development and Medicine worldwide.

Efficacy and safety profile of Actilyse® in restoring catheter function

The efficacy of Actilyse® (alteplase) 2mg in restoration of function to CVADs implanted in patients has been studied in two key clinical studies. Across these pivotal trials2,3 (COOL-1* and COOL-2 studies), 75 percent of patients with occlusions present for less than 14 days had restored function after one dose and 85 percent had function restored after up to two doses.1 In addition, the efficacy of Actilyse® (alteplase) in a dose of up to 2mg in restoration of function to CVADs in paediatric patients was studied in the CAPS (Cathflo Activase Paediatric Study).4 The overall rate of catheter function restoration was 83 percent, similar to that observed in the COOL-2 study. (*Subjects with duration of occlusion >7 days were excluded in COOL-1)

The safety profile of Actilyse® (alteplase) 2mg has been found to be very favourable in this critically ill patient cohort who require CVAD treatment.1-4 Adverse events seen in the pivotal clinical trials included sepsis (0.4 percent), major haemorrhage (0.4 percent), gastrointestinal bleeding (0.3 percent), and venous thrombosis (0.3 percent) .1

Please be advised

This release is from Boehringer Ingelheim Corporate Headquarters in Germany. Please be aware that there may be national differences between countries regarding specific medical information, including licensed uses. Please take account of this when referring to the information provided in this document. This press release is not intended for distribution within the U.S.A.

About Actilyse®

Actilyse® (active ingredient: alteplase), a recombinant tissue plasminogen activator (rt-PA), is a genetically engineered version of naturally occurring tissue plasminogen activator, which has the biological function of removing small clots that routinely form in the bloodstream. In addition to the alteplase 2mg vial approved for the thrombolytic treatment of occluded central venous access devices, alteplase was first approved in 1987 in major countries across the globe for the thrombolytic treatment of acute myocardial infarction, followed by subsequent approvals in the indications acute massive pulmonary embolism and acute ischaemic stroke (registered indications can vary across the globe).

The alteplase 2mg vial is recommended for the clearance of occluded catheters only. When alteplase is administered for restoration of dysfunctional catheters according to the instructions, circulating plasma levels of alteplase are not expected to reach pharmacologic concentrations. For treatment of myocardial infarction, pulmonary embolism or acute ischaemic stroke, treatment must be performed with the appropriate precautions and according to the recommended comparably higher dosages in these indications for which Actilyse® is also approved.

The most frequent adverse reaction associated with all thrombolytics in all approved indications is bleeding. Alteplase has not been studied in patients with occluded catheters known to be at risk for bleeding events that may be associated with the use of thrombolytics, therefore, caution should be exercised with patients who have active internal bleeding or who have an increased risk of haemorrhages.

Actilyse® (alteplase) is registered in over 85 countries across the world. It is marketed already by Boehringer Ingelheim outside the U.S.A., Canada and Japan for the indications acute myocardial infarction, acute massive pulmonary embolism, and acute ischaemic stroke. In the U.S.A., alteplase is marketed by Genentech, Inc. (Boehringer Ingelheim's marketing partner in the U.S.A. for alteplase) under the tradename Activase® and for catheter clearance under the tradename Cathflo®Activase®. Alteplase is also available in Canada where it is marketed by Roche Canada.

About CVADs

Central venous access devices are being used more frequently as many critical medical therapies require their use. When CVADs become occluded, administration of critical therapies must be delayed until the blockage can be cleared or the CVAD can be replaced. Such delays may cause serious complications for the patient, as caregivers are unable to inject or infuse solutions or withdraw blood.

Current treatments for CVAD occlusion include surgically removing and replacing the CVAD, which can be an uncomfortable, expensive and a potentially risky procedure for patients. With alteplase 2mg, healthcare professionals can administer a pharmaceutical therapy to break down the thrombus and restore function to the CVAD.

About Boehringer Ingelheim

The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 135 affiliates in 47 countries and 39,800 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.

In 2007, Boehringer Ingelheim posted net sales of 10.9 billion euro while spending one fifth of net sales in its largest business segment Prescription Medicines on research and development. http://www.boehringer-ingelheim.com

References:

1. Semba CP, Deitcher SR, Li X, et al. Treatment of occluded central venous catheters with alteplase: Results in 1,064 patients. J Vasc Interv Radiol 2002;13:1199-1205.

2. Ponec D, Irwin D, Haire WD, et al. Recombinant tissue plasminogen activator (alteplase) for restoration of flow in occluded central venous access devices: A double-blind placebo-controlled trial the Cardiovascular thrombolytic to Open Occluded Lines (COOL) efficacy trial. J Vasc Interv Radiol 2001;12:951-955.

3. Deitcher SR, Fesen MR, Kiproff PM, et al. Safety and efficacy of alteplase for restoring function in occluded central venous catheters: Results of the Cardiovascular thrombolytic to Open Occluded Lines trial. J Clin Oncol 2002;20:317-324.

4. Blaney M, Shen V, Kerner JA, et al. Alteplase for the treatment of central venous catheter occlusion in children: results of a prospective, open-label, single-arm study (the Cathflo Activase Pediatric Study). J Vasc Intervent Radiol 2006;17: 1745-1751.

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