Violative Advertising and Promotional Labeling Letter

Reteplase (Retavase) (Centocor, Inc)

May 30, 2003

Mr. Christopher D. Zalesky
Centocor, Inc.
200 Great Valley Parkway
Malvern, PA 19355

Dear Mr. Zalesky:

Through routine monitoring and surveillance, the Advertising and Promotional Labeling Branch (APLB) in the Food and Drug Administration's Center for Biologics Evaluation and Research (CBER) has identified promotional materials for your product, Retavase (Reteplase) that violate the Federal Food, Drug, and Cosmetic Act (Act) and its implementing regulations. APLB has reviewed numerous promotional pieces including a 2002 Slim Jim (RP02015) and a Dosing Card (RP02071) and has concluded that these materials contain false and/or misleading claims about Retavase or its competing products. Copies of all referenced materials are enclosed.

1. The 2002 Slim Jim (RP02015, Tab A) includes pages titled, “Retavase - Efficacy Confirmed in GUSTO V” and “Retavase -Safety Confirmed in GUSTO V.” On these pages are two bar graphs supporting that Retavase achieved a 5.9% mortality rate at 30 days and a 0.59% ICH rate in the GUSTO V trial. These claims are false and/or misleading because the GUSTO V trial data do not constitute substantial evidence or substantial clinical experience. In fact, the GUSTO V trial of retavase vs. retavase+abciximab did not provide substantial evidence of efficacy for either treatment group. You should immediately cease any further dissemination of all advertising and promotional materials that contain these claims and similar presentations.

2. Under the Retavase logo, the statement, “Superior Reperfusion in AMI,” is repeated as a tagline associated with the proprietary and established name throughout your promotional materials. This claim falsely implies that Retavase is superior to all reperfusion therapies in AMI, which has not been demonstrated by substantial evidence or substantial clinical experience. In fact, data from the RAPID-II trial support this claim for only one therapy - retavase vs. alteplase. Consequently, in the absence of any data that Centocor may have to support this claim, you should immediately cease any further dissemination of all advertising and promotional materials that contain these claims and similar presentations or revise them to accurately identify the therapy for which data exists. If Centocor has data to support this claim, you should submit it within 30 days of the date of this letter to CBER for review.

3. The title, “The Only Fibrinolytic Proven Superior to tPA in Restoring TIMI 3 Flow” is misleading because it does not specify to which of the multiple types of tissue plasminogen activators you claim superiority. Data from the RAPID-II trial support this claim for only one therapy - retavase vs. alteplase. You should immediately cease any further dissemination of all advertising and promotional materials that contain these claims and similar presentations or revise them to accurately identify the therapy for which data exists.

4. In the 2002 Slim Jim (RP02015, Tab A) insert entitled, “Unique Design,” the title “Unique Molecular Design for Rapid and Safe Reperfusion” is false and/or misleading. FDA is aware of no data consisting of substantial evidence or substantial clinical experience establishing that the molecular design of the products tested correlates with the speed and safety of reperfusion. If Centocor has data to support this claim, you should submit the data within 30 days of the date of this letter to CBER for review. In the absence of such data, you should immediately cease any further dissemination of all advertising and promotional materials that contain these claims and similar presentations. A title such as “Unique Molecular Design” would be acceptable.

5. The dosing card (RP02071, Tab B) contains complex tables regarding the comparative dosing of Retavase vs. Alteplase, and Retavase vs. Tenecteplase. These tables are misleading because they misrepresent and exaggerate the complexity of the approved Alteplase and Tenecteplase dosing by listing every dose for weights in 2-kilogram increments. However, for example, as noted in the approved package insert (PI) for Alteplase, “the dose is to be weight-adjusted only for patients who weigh 67 kg or less, but does not need to be weight-adjusted for patients who weigh > 67kg.” Therefore, please revise your advertising and promotional materials accordingly that contain these claims and similar presentations.

In addition, the above false and/or misleading claims continue to be used in the following promotional materials:

• One dose for All Poster (RP02028)
• Mega trials flashcard (RP02014)
• ACEP Convention Ads (RP02073)
• Convention Panels A, B, C, F, G and I (RP02029-02031, RP02034-02036)
• St. Joseph’s Flashcard (RP01046)
• Nurses Slide Kit (RP02040)
• Slide Set - New Strategies for AM/ACS Management (RP02018).

This letter is not intended to be an all-inclusive list of deficiencies associated with your promotion of the above product. It is your responsibility to ensure that all materials distributed within the United States are in conformance with each requirement of the Act and applicable regulations.

You should respond within ten business days of the date of this letter. Your response should include a statement of your intent to comply with each of the above, a list of all similarly violative materials, a description of the method for discontinuation and the discontinuation date.

Your response should be directed to Mr. Glenn N. Byrd, Chief, APLB, at the address listed below. Should you have any questions or concerns involving this matter, please contact Dr. Yongkai Weng, Consumer Safety Officer at 301-827-3028.

Sincerely,

----- signature -----

Mary A. Malarkey
Director
Division of Case Management
Office of Compliance and Biologics Quality
Center for Biologics Evaluation and Research

Enclosures

Last Updated: 6/3/2003

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