Released by FDA: 7/9/01.  Posted by FDA:  7/26/01

Christine Duffy Smith 
Promotional Regulatory Affairs, Director 
AstraZeneca Pharmaceuticals LP 
1800 Concord Pike 
P.O. Box 15437 
Wilmington, DE 19850-5437

RE:   IND # [confidential, deleted by FDA] ZD1839 
                    [confidential, deleted by FDA] ZD0473 
                    [confidential, deleted by FDA] ZDl694 (tomudex)
                    [confidential, deleted by FDA] ZD9238 (faslodex) 
         NDA# 20541 Arimidex (anastrozole) tablets 
         MACMIS 1D# 10135

Dear Ms. Duffy Smith:

This letter notifies AstraZeneca Pharmaceuticals LP (AstraZeneca) that the Division of Drug Marketing, Advertising, and Communications (DDMAC) has identified promotional activities that are in violation of the Federal Food, Drug, and Cosmetic Act (Act) and its implementing regulations.   Specifically, AstraZeneca is promoting Arimidex for an unapproved use and promoting its investigational new drugs, ZD1839, ZD0473, ZD1694 (tomudex), and ZD9238 (faslodex), as safe or effective.   Our specific objections follow:

Promotion of Unapproved Uses

Arimidex is indicated for the first-Line treatment of postmenopausal women with hormone receptor positive or hormone receptor unknown locally advanced or metastatic breast cancer and for the treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy. AstraZeneca distributed an abstract entitled The Combined Use of Goserelin and Anastrozole as Second Line Endocrine Therapy in Premenopausal Women with Advanced Breast Cancer - a Study of its Clinical and Endocrine Effects at their commercial exhibit at the 37^th American Society of Clinical Oncology (ASCO) Annual Meeting held in San Francisco, California in May 2001.   The abstract states "This study shows that Z [Zoladex (goserelin)] + A [Arimidexj induces therapeutic remission in a reasonable proportion of premenopausal women with advanced breast cancer who have progressed on Z+T [tamoxifen].  The clinical therapeutic effects are associated with demonstrable endocrine changes including a dramatic reduction of E2 levels seen in post-menopausal women receiving A alone.”

The disseminated materials are violative and show that AstraZeneca intends for Arimidex to be used for an unapproved new use. Further, the small statement in the lower right corner of the disseminated abstract (“For Medical Information Only -- Not approved in the US”) does not correct the violative promotion of an unapproved use for Arimidex in the commercial exhibit hall.

Promotion of Investigational Drugs

The AstraZeneca booth in the commercial exhibit hall of the May 2001, ASCO Annual Meeting includes convention panels describing the safety or effectiveness of ZD1839 and ZD1694 (tomudex), that are investigational drugs.   Moreover, AstraZeneca disseminated promotional materials in two plastic containers, as well as copies of abstracts, that were available throughout the commercial exhibit area.   One plastic container is labeled “ZD1839 (‘Iressa’) M3dical Information Pack” and contained eighteen color copies of poster presentations and two slide kit handouts that made conclusions about the safety or efficacy of this investigational drug.   The other container is labeled “A new generation platinum agent Medical Information Pack” and also contained numerous abstracts and color copies of poster presentations that made conclusions about the safety or efficacy of the investigational drug ZD0473.   In addition, other loose abstracts, disseminated at the commercial booth, made conclusions about the safety or efficacy of the investigational drug ZD9238 (faslodex).

These convention panels and promotional materials include conclusionary statements such as:

ZD1839

“ZDI 839 in combination with standard cytotoxics was well tolerated and showed enhanced tumor activity compared with treatment with either ZD1839 or cytotoxics alone."

“ZD1839 in combination with standard cytotoxics was associated with a significant increase in survival in vivo, particularly in combination with paclitaxel.”

“Orally administered Z01839 is active against central nervous system tumors with limited or no systemic toxicity.”

“ZD1839 oral administration was well tolerated in patients with solid malignant tumors.”

ZD1694 (tomudex)

“Specific TS inhibitor active in a range of malignancies”

“Single agent activity in phase 2 studies in colorectal, nscl, pancreatic, breast, and ovarian cancers”

“Activity seen in phase 2 chemoradiation studies of raltitrexed [tomudex] alone and in combination with oxaliplatin as preoperative therapy for rectal cancer”

“Activity seen in the first and second-line therapy of advanced colorectal cancer in combination with oxaliplatin”

“Manageable toxicity profile” 

ZD0473

“There was evidence of antitumor activity in ovarian cancer patients” 

"ZD0473 has a predictable and manageable toxicity profile”

ZD9238 (faslodex)

“In conclusion, FAS [faslodex] was at least as effective as ADX [Arimidex], with a non-significant numerical increase OR observed.”

Section 21 CFR 312.7 states, among other things, that an investigational new drug may not be promoted as being safe or effective for uses under investigation.   Therefore, the above claims are in violation of the Act,

Requested Action

AstraZeneca should immediately cease the distribution of these and other similar promotional materials for the above drugs that contain the same or similar claims or presentations.   AstraZeneca should submit a written response to DDMAC on or before July 23, 2001, describing its intent and plans to comply with the above.   In its letter to DDMAC, AstraZeneca should include the date on which this and other similarly violative materials were discontinued.

AstraZeneca should direct its response to me by facsimile at (301) 594-6771 or by written communication at the Division of Drug Marketing, Advertising, arid Communications, HFD-42, Rm. 17B-20, 5600 Fishers Lane, Rockville, MD 20857. In all future correspondence regarding this matter, please refer to MACMIS ID # 10135 in addition to the NDA number.   DDMAC reminds AstraZeneca that only written communications are considered official.

Sincerely,

 

Joseph A. Grille, Pharm.D. 
Regulatory Review Officer 
Division of Drug Marketing, 
   Advertising, and Communications