Released by FDA: 11/9/01.  Posted by FDA:  11/28/01

June Bray
Director, Regulatory Affairs 
Berlex Laboratories, Inc. 
340 Changebridge Road 
PO Box 1000
Montville, NJ 07045-1000

RE:  NDA 20-570
       Quadramet (Samarium Sm-153 lexidronam) Injection 
       MACMIS # 10,389

Dear Ms. Bray:

This letter objects to Berlex Laboratories, Inc.'s (Berlex) dissemination of violative promotional materials for Quadramet.   Specifically, as part of its routine monitoring program, the Division of Drug Marketing, Advertising, and Communications (DDMAC), has identified a brochure (01-531-1070) and videotape (01-531-1080) submitted under cover of Form FDA 2253 that are false or misleading under the Federal Food, Drug, and Cosmetic Act and its implementing regulations.   Our specific objections follow:

Unsubstantiated Claims

Promotional materials are misleading if they claim that a drug is better, more effective, or useful in a broader range of conditions or patients than has been demonstrated by substantial evidence.  Your brochure entitled, "Metastatic prostate cancer: treatment with Quadramet," describes a patient with metastatic prostate cancer to the bone. Specifically, your brochure describes that this patient presented with extreme pain, rated 10 on a scale of 10, despite opioid therapy, and became pain free (0 on a scale of 10) after 5 days of treatment with Quadramet.  Your brochure also claims that the patient has remained pain free for 16 months since Quadramet therapy.  However, the approved product labeling (PI) for Quadramet presents the results of clinical trials that have much different results.  Specifically, treatment with Quadramet frequently resulted in increased short-term pain followed by moderate pain relief in some patients. For example, 4 weeks after administration of Quadramet, 41 % of patients had some relief from pain, and 14% had marked relief of pain.

You also claim in the brochure that all of the patient's pain medication was stopped 3 days after treatment with Quadramet and that "this patient has not required additional prescription pain medication since receiving Quadramet in December 1999."  This claim is not consistent with the PI that states in trial A, morphine equivalent analgesic use increased from baseline with both Quadramet and placebo.  In study B, the placebo treated patients increased their use o£ opioid analgesics, while the Quadramet treated patients decreased (but did not discontinue) their use of opioid analgesics.

Therefore, your brochure that implies that 5 days after treatment with Quadramet, patients will have 100% pain relief for an extended time as defined as a score of 0 on a scale of 10, without prescription pain medications is misleading.  Only a small percent of treated patients would be expected to have the very successful outcome you describe.  Your presentation of the information on the back page of the brochure that "patients notice improvement for up to 4 weeks" and that "pain relief usually lasts an average of 16 weeks" fails to correct the overwhelming impression from the presentation of the case study that Quadrarnet is more effective than has been shown by substantial evidence.

You make similar, unsubstantiated claims in your videotape entitled, "Every Patient's Right -- Understanding and managing bone pain."  In the videotape, you claim in patient testimonials that one can expect to be pain free without opioid analgesics after achninistration of Quadramet.  As explained above, these patient experiences are not representative of the results seen in the vast majority of patients studied in clinical trials. Therefore, your videotape is misleading because it claims that Quadramet is more effective than has been shown by substantial evidence.

Requested Actions

In order to address these objections, we request that you immediately cease the dissemination of the violative brochure and videotape and all similar promotional materials that contain the same or similar messages.

You should respond in writing to us regarding this issue by November 26, 2001.  Your response should include Berlex's intent to comply with the above request, the date that it ceased disseminating these and any other violative promotional materials with the same or similar messages, and a list of the discontinued materials.

If you have any questions, please contact me by facsimile at (301) 594-6771, or by written communication at the Division of Drug Marketing, Advertising, and Communications, HFD-42; Room 178-20; 5600 Fishers Lane; Rockville, MD 20857. DDMAC reminds Berlex that only written communications are considered official.

In all future correspondence regarding this matter, please refer to MACMIS # 10,389 and NDA 20-570.

Sincerely,

Warren Rumble 
Regulatory Review Officer 
Division of Drug Marketing, 
Advertising, and Communications