Released by FDA: 9/14/00.  Posted by FDA:  9/25/00

Gregory G. Enas, Ph.D. 
Director, U.S. Regulatory Affairs 
Eli Lilly and Company 
Lilly Corporate Center 
Indianapolis, IN 46285

RE:   NDA#20-815 
         Evista (raloxifene HCl) Tablets 
         MACMIS ID# 9307

Dear Dr. Enas:

This letter refers to Eli Lilly and Company’s (Lilly) August 21, 2000, submission to the Division of Drug Marketing, Advertising, and Comunications (DDMAC) under cover of Form FDA 2253 of a direct-to-consumer broadcast advertisement (item number RA 18086 10154789) for Evista tablets.  DDMAC has reviewed this disseminated advertisement and has determined that it is in violation of the Federal Food, Drug, and Cosmetic Act and its implementing regulations.  Specifically, we object for the following reasons:

Overstatement of Benefit

The advertisement is misleading because it mischaracterizes the nature of osteoporosis, resulting in an overstatement of Evista’s benefits.

Fur example, claims such as “A disease of thin, weak bones that can fracture and take away your independence” and “Don’t let osteoporosis stop you” misleadingly imply that having osteoporosis is, in itself,  debilitating.  However, while osteoporosis increases the risk of fracture, not every osteoporotic patient will suffer a fracture.  In addition, those who do will not necessarily suffer any loss of independence because many osteoporotic fractures are asymptomatic.  Furthermore, while Evista may reduce the risk of fracture, it does not eliminate it altogether. therefore. these claim  is misleadinglv imply outcomes and guarantees of efficacy for Evista that have not been demonstrated by substantial evidence.

Similarly, the claim “Up to 1/2 of women over 50 will break a bone due to osteoporosis” is misleading because it lacks context that distinguishes between symptomatic fractures of the hip or wrist and asymptomatic vertebral fractures. Vertebral fractures are the most common type of osteoporotic fractures in postmenopausal women.  Yet, most vertebral fractures are not symptomatic and do not interfere with a patient’s independence.  The approved product labeling (Pl) for Evista only cites evidence of Evista’s effect on vertebral fractures.  It does not include any evidence that Evista decreases the incidence of hip or wrist fractures.  Therefore, this presentation misleadingly suggests that Evista provides greater efficacy than demonstrated by substantial evidence.

Broadening of the Patient Population

The advertisement is misleading because it implies that Evista is useful for a broader population than that for which it is indicated.  For example, the claim “if you’re past menopause you should know about Evista” creates a misleading impression that all postmenopausal women will develop osteoporosis.  However, menopause alone does not cause osteoporosis and only those with risk factors are candidates for Evista therapy.  Thus, the claim misleadingly overstates the population appropriate for Evista therapy by implying that all women will develop osteoporosis at menopause.

Although you provide risk factors for the development of osteoporosis as supers in frames six and seven of the storyboard, your presentation lacks sufficient prominence to be readable.  Thus, the supers do not adequately correct the misleading characterization of the nature of osteoporosis and do not adequately communicate the appropriate patient population for which Evista is indicated.

Lack of Prominence for Complete indication and Contextual Information

The presentation of the indication is misleading because the necessary context does not adequately accompany the indication.  The approved indication for Evista includes the statement “For either osteoporosis treatment or prevention. supplemental calcium and/or vitamin D should he added to the diet if daily intake is inadequate.”  The advertisement presents this information by a super in small type with poor contrast in frames eighteen and nineteen.  The super does not adequately qualify the Indication information presented earlier in frames nine and ten.  Furthermore, it lacks sufficient prominence to be readable and its presentation is further minimized by the two accompanying supers of adequate provision information appearing in these frames

Inadequate Risk Disclosure

The Pl contains a precaution that the concomitant use of Evista with systemic estrogens is not recommended.  Because a significant number of postmenopausal women use estrogen replacement therapy,  failure to disclose this precaution in this broadcast advertisement misleadingly implies that Evista is safer than has been demonstrated.

In addition, the presentation of adverse event information is misleading because the phrase “most women did riot experience these” minimizes the incidence of the side effects associated with Evista therapy.  For example, hot flashes occurred in 24.6% of the women who received Evista during the prevention trials.  The presentation of this phrase without accompanying contextual information is misleading because it minimizes the importance of this adverse event that occurs in a significant percentage of patients

Requested Actions

DDMAC requests that Lilly immediately discontinue the broadcast of this violative advertisement and all other promotional materials that contain the same or similar violative claims or representations.  DDMAC requests that Lilly submit a written response to this letter no later than September 28, 2000, including your plan to comply with DDMAC’s request.  Your written response should include a list of all materials that you have discontinued and the date that they were discontinued.

If you have any questions or comments, please contact me by facsimile at (301) 594-6771 or at the Food and Drug Administration, Division of Drug Marketing, Advertising, and Communications, HFD-42. Rm. 17B-20, 5600 Fishers Lane, Rockville, MD 20857.

DDMAC reminds you that only written communications are considered official. In all future correspondence regarding this particular matter, please refer to MACMIS ID #9307 in addition to the NDA number.

Sincerely,

Margaret M. Kober, R.Ph. 
Regulatory Review Officer 
Division of Drug Marketing. 
    Advertising, and Communications