Released by FDA: 6/28/00.  Posted by FDA:  7/17/00

Howard T. Holden, Ph.D. 
Vice President 
Regulatory Affairs and Compliance 
Ligand Pharmaceuticals, Inc. 
10275 Science Center Drive 
San Diego, CA 92121-1117

RE:    NDA 21-055 
          Targretin® (bexarotene) capsules 
          MACMIS lD# 9044

Dear Dr. Holden:

As part of its routine monitoring and surveillance program, the Division of Drug Marketing, Advertising, and Communications (DDMAC) has identified certain promotional materials for Targretin by Ligand Pharmaceuticals (Ligand) that are in violation of the Federal Food, Drug, and Cosmetic Act (the Act).  Specifically, we refer to Ligand’s convention panels for Targretin that were used at the 36th Annual American Society of Clinical Oncology (ASCO) Meeting in New Orleans on May 20-23, 2000. These panels (TAR123A-LIG) were submitted under cover of Form FDA 2253 on June 9, 2000.

Misleading Efficacy Claims

These convention panels display before/after photos of cutaneous manifestations of cutaneous T-cell lymphoma (CTCL), as well as headers that claim “all-stage efficacy” and “proven tumor regression at all stages of CTCL.”  All of the photos depict patients who had favorable responses to Targretin.  However, given the 1.6% complete response and 30% partial response of the 62 patients in the clinical studies, the photos and claims are misleading since many patients did not achieve such favorable results. Targretin therapy produces various individual responses on cutaneous lesions; while one lesion may improve, others may worsen.  The overwhelming impression that all lesions will improve is misleading because it implies greater effectiveness than demonstrated by substantial evidence.  In addition, your presentation of text about tumor response rates does not overcome the misleading impression created by the photos and claims.

Lack of Fair Balance

Promotional materials are lacking in fair balance if they fail to present information relating to side effects and contraindications with a prominence and readability reasonably comparable with the presentation of information relating to effectiveness of the drug, taking into account all implementing factors such as typography, layout, contrast, headlines, paragraphing, white space, and any other techniques apt to achieve emphasis.  The convention panels lack fair balance because efficacy information is prominently presented with colors, photos, and enlarged fonts while risk information is presented as paragraphed text at the bottom of the panel.

Failure to Comply with 314.81(b)(3)(i)

Since the convention panels were not submitted on Form FDA 2253 at the time of initial dissemination, Ligand has violated the post-marketing reporting requirements of the Act.

Conclusions and Requested Actions

We acknowledge your letter that accompanied the aforementioned Form FDA 2253 submission, which stated that Ligand has discontinued use of the convention panels and does not intend to use them again.  Ligand should immediately cease dissemination of all other promotional materials that contain these or similar claims.  Ligand should submit in writing, on or before July 12, 2000, a description of the steps that will be taken to comply with the above request.  Ligand should also include a list of all similarly violative materials being discontinued, as well as the date of discontinuation.

Ligand should direct its response to me by facsimile at (301) 594-6771, or by written communication at the Food and Drug Administration; Division of Drug Marketing, Advertising, and Communications, HFD-42; Room 17B-20; 5600 Fishers Lane; Rockville, MD 20857.  We remind you that only written communications are considered official.

In all future correspondence regarding this matter, please refer to MACMIS lD# 9044 and NDA 2 1-055.

Sincerely,

Jean-Ah Choi, Pharm.D. 
Regulatory Review Officer 
Division of Drug Marketing, 
   Advertising, and Communications