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U.S. Department of Health and Human Services

Vaccines, Blood & Biologics

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BCG Live (Intravesical), TheraCys

January 13, 2004

VIA FASCIMILE AND CERTIFIED MAIL
RETURN RECEIPT REQUESTED

Luc Kuykens, MD, MPH, DTM
Vice President, Regulatory Affairs
North America
Aventis Pasteur Inc
Discover Drive
Swiftwater, PA 18370

Re: BLA STN #103289

TheraCys [BCG Live (Intravesical)]

Dear Dr. Kuykens:

The Advertising and Promotional Labeling Branch (APLB) in the Food and Drug Administration's Center for Biologics Evaluation and Research (CBER) has identified a Faxable Flashcard (MKT8063) for TheraCys [BCG Live (Intravesical)]. The flashcard is false or misleading under section 502(a) of the Federal Food, Drug, and Cosmetic Act (the Act) (21 U.S.C. § 352(a)) because it contains a representation or suggestion that TheraCys is better or more effective than has been demonstrated by substantial evidence or substantial clinical experience.

Background

TheraCys is a freeze-dried preparation made from the Connaught strain of Bacillus Calmette and Guerin, which is an attenuated strain of Mycobacterium bovis. According to the approved labeling (PI), TheraCys is indicated for the treatment and prophylaxis of carcinoma in situ (CIS) of the urinary bladder, and for the prophylaxis of primary or recurrent stage Ta and/or T1 papillary tumors following transurethral resection (TUR). TheraCys is not recommended for stage TaG1 papillary tumors, unless they are judged to be at high risk of tumor recurrence. The drug is not indicated as an immunizing agent for the prevention of tuberculosis.

Unsubstantiated Effectiveness Claim

In the middle of the first page of the flashcard a header, in large type, states: "TheraCys is proven effective[.]" Below this, in smaller type, the flashcard states, "In a randomized trial with TheraCys vs doxorubicin
(n=131)1[.]" Directly following that statement, the flashcard states:

  • "A complete response* was obtained in 45 of 64 BCG-treated patients (70%) vs 23 of 67 patients (34%) treated with doxorubicin (P<0.001)." This is followed by a large box with "70%" presented in large, bold type equivalent to the large type of the preceding header, "TheraCys is proven effective[.]"

     

  • "Of the 70% of patients who received TheraCys and had a complete response, an estimated [emphasis added] 63.9% will be free of disease for 5 years after treatment1[.]" This is followed by a large box with "63.9%" presented in large, bold type equivalent to the large type of the preceding header, "TheraCys is proven effective[.]"

The flashcard thus represents or suggests that 70 percent of all patients who receive TheraCys will have a complete response after treatment. To FDA's knowledge, this has not been demonstrated by substantial evidence or substantial clinical experience. The cited study evaluated TheraCys in the treatment and prophylaxis of carcinoma in situ (CIS) of the urinary bladder. The study also evaluated the drug in prophylaxis of primary or recurrent stage Ta and/or T1 papillary tumors following transurethral resection (TUR), but found lower effectiveness rates for that indication.

The asterisk statement that the complete responses were confirmed by biopsy and analysis after therapy "for bladder cancer (carcinoma in situ [CIS])" is not adequate to address the overall misleading message communicated by the flashcard. This statement does not convey with sufficient clarity that the claimed effectiveness rate of 70 percent applies only in bladder cancer. Moreover, the reference to bladder cancer appears embedded with other text in small print at the bottom of the first page of the flashcard.

The flashcard also represents or suggests that approximately 63.9 percent of patients who had a complete response to TheraCys will be free of disease for five years after treatment. FDA is not aware of substantial evidence or substantial clinical experience substantiating this claim. The cited study did not have five-year freedom from disease as an endpoint. Indeed, the study period was two years, and the five-year figure is based on an estimate achieved by extrapolating from the two-year data.

Conclusion and Requested Actions

The flashcard misbrands TheraCys within the meaning of section 502(a) of the Act (21 U.S.C. § 352(a)) because it represents that TheraCys is more effective for a broader range of indications than has been demonstrated by substantial evidence or substantial clinical experience and is, therefore, false or misleading.

APLB requests that Aventis Pasteur immediately cease the dissemination of promotional materials for TheraCys that contain claims the same as, or similar to, those described above. Please submit a written response to this letter within 10 business days of the date of this letter, describing your intent to comply with this request, listing all promotional materials for TheraCys that contain claims the same as or similar to those described above, and explaining your plan for discontinuing use of such materials.

If you have data constituting substantial evidence or substantial clinical experience to support your claims, please submit those data to CBER for review.

Please direct your response to Mr. Glenn N. Byrd, Chief, APLB, at the following address:

Center for Biologics Evaluation and Research
Office of Compliance and Biologics Quality
Division of Case Management
Advertising and Promotional Labeling Branch, HFM-602
1401 Rockville Pike
Rockville, MD 20852-1448.

In all future correspondence regarding this matter, please refer to the BLA number. We remind you that only written communications are considered official. Should you have any questions or concerns involving this matter, please contact Dr. Yongkai Weng, Consumer Safety Officer at 301-827-3028.

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 comply with each applicable requirement of the Act and FDA regulations. If you choose to revise your promotional materials, APLB is willing to assist you in assuring that your revised materials comply with applicable provisions of the Act by reviewing your revisions before you use them in promotion.

Sincerely,

----- signature -----

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

Enclosure
TheraCys Faxable Flashcard (MKT8063)