FDA Approves Cathflo Activase 'Alteplase' to Restore Function to Central Venous Access Devices as Assessed by the Ability to Withdraw Blood.

Business Editors/Health & Medical Writers

-- Cathflo Activase Now the Only Marketed Available Thrombolytic Agent

Indicated To Restore Function to Central Venous Access Devices --

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Sept. 4, 2001

Genentech, Inc. (NYSE:DNA), announced today that its thrombolytic agent Cathflo(TM) Activase(R) (Alteplase), a tissue plasminogen activator (t-PA), has been approved by the U.S. Food and Drug Administration (FDA) for the restoration of function to central venous access devices (CVADs), as assessed by the ability to withdraw blood. Cathflo Activase, available in a 2 mg single-patient-use vial, is the only marketed thrombolytic available for this indication and offers medical professionals a viable treatment option for a CVAD complication that can hinder patient care.

"The approval of Cathflo Activase provides Genentech an opportunity to address an important medical need for patients who rely on central venous access devices for their medical care, and represents an excellent business opportunity to expand our successful Activase cardiovascular franchise into a new arena," said Arthur D. Levinson, Ph.D., Genentech's chairman and chief executive officer.

"The availability of Cathflo Activase may help patients avoid surgical removal and replacement of blocked CVADs," said COOL-2 pivotal trial lead investigator Steven R. Deitcher, MD, director of clinical thrombosis and vascular research in the Department of Cardiovascular Medicine, section of vascular medicine and staff physician in the Department of Hematology and Medical Oncology at The Cleveland Clinic in Ohio. "Most importantly, an open CVAD line allows for the uninterrupted administration of critical medical therapies essential to many life-saving treatment regimens."

Central venous access device, or CVAD, is a broad term that includes many types of catheters (thin, flexible hollow tubes) that are inserted into and positioned within a vein in the body to deliver therapies or withdraw blood. An estimated five million CVADs are placed each year in the U.S. to provide patients with life-saving medications and critical treatment. CVAD occlusions or blockages due to formation of a blood clot (thrombus) within or at the tip of the CVAD catheter are a common problem that can block the administration of these therapies to patients. It is estimated that up to 25 percent of CVADs become occluded and that 60 percent of those occlusions are caused by the formation of a blood clot. Cathflo Activase works by activating plasminogen, which dissolves fibrin (a substance that causes blood to clot), breaking down the thrombus and restoring function to the CVAD.

COOL Trials

FDA approval of Cathflo Activase is based on two Phase III clinical trials designed to assess its safety and efficacy in restoring function to CVADs that had become occluded due to a blood clot: the COOL (Cardiovascular thrombolytic to Open Occluded Lines) efficacy trial and the COOL-2 safety trial. Neither study included patients with hemodialysis catheters, known mechanical occlusions and those at high risk for bleeding or embolization.

The COOL efficacy trial, a Phase III, six-month, randomized, placebo-controlled, double-blind study, enrolled 150 adult and pediatric (ages 2-16) patients with CVAD occlusion up to 24 hours. In this study, Cathflo Activase or placebo was instilled directly into the lumen opening (tube of the catheter that carries fluid through a CVAD directly to the vein), for a dwell time of 120 minutes. Patients with CVADs that remained occluded after an initial dose of Cathflo Activase or placebo were administered a second dose of Cathflo Activase as either a first active dose (for placebo group) or follow-up dose (treatment group).

The study found that patients treated with up to two active doses had restored CVAD function. After the initial dose of Cathflo Activase, 67 percent (n=51) of the patients' CVADs were functional, compared to 16 percent (n=12) restored in the placebo group. A total of 88 percent (n=112) of Cathflo Activase patients treated with either a double-dose or single-dose had restored CVAD function. These data have been published in the August issue of the Journal of Vascular and Interventional Radiology (JVIR).

The COOL-2 trial, a Phase IIIb, single-arm, open-label study, enrolled 995 adult and pediatric (ages 2-16) patients with CVAD occlusion present for any duration to determine the safety of Cathflo Activase for restoring function to occluded CVADs. The study demonstrated that the treatment has an acceptable safety profile in CVAD clearance and reconfirmed the product's efficacy, restoring CVAD function to 85 percent (n=844) of patients after up to two doses.

In the two trials only serious adverse events thought to be possibly related to the study drug were reported. The most serious adverse events reported were sepsis, GI bleeding and venous thrombosis.

Cathflo Activase and Activase(R) (Alteplase)

Cathflo Activase will be marketed using a different dose and dosing regimen from Activase(R) (Alteplase). Following Abbott Laboratories' removal of urokinase from the CVAD clearance market in late 1998, Genentech began working with the FDA to bring Activase to the market for use in occluded CVADs.

CVADs Increasingly Important in Providing Needed Therapies

Central venous access devices are being used more frequently as many critical medical therapies require their use. Chemotherapy treatments for cancer patients, antibiotics for patients with severe bacterial infections, and supplements for patients at risk for malnutrition because they cannot receive nutrients via the digestive tract can all be administered through a CVAD. The use of Cathflo Activase has not been studied in hemodialysis catheters and safety and efficacy have not been established.

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 Cathflo Activase health care professionals can now administer a pharmaceutical therapy to breakdown the thrombus and restore function to the CVAD.

Genentech, Inc. is a leading biotechnology company that discovers, develops, manufactures and markets human pharmaceuticals for significant unmet medical needs. Fourteen of the approved products of biotechnology stem from or are based on Genentech science. Genentech markets eight products directly in the United States. The company has headquarters in South San Francisco, California, and is traded on the New York Stock Exchange under the symbol DNA.