Released by FDA: 11/15//01.  Posted by FDA:  11/28/01

Linda Fenney, M.D. 
Senior Vice President 
Research, Product Development and Regulatory Affairs 
Connetics Corporation
3400 West Bayshore Road 
Palo Alto, CA 94303

RE:   Luxig^TM (betamethasone valerate) Foam, 0.12% 
         NDA 20-934
         MACMIS 113#10501

Dear Dr. Fenney:

This letter objects to Connetics Corporation's (Connetics) dissemination of violative promotional materials for Luxid (betamethasone valerate) Foam.   As part of its monitoring program, the Division of Drug Marketing, Advertising and Communications (DDMAC) has become aware of professional promotional materials for Luxiq that are false or misleading, in violation of the Federal Food, Drug, and Cosmetic Act (Act) and its implementing regulations.  Specifically, DDMAC objects to Connetics dissemination of the following promotional labeling pieces, described as Luxiq "Case Studies" (PRM-LUX1-082R, PRM-LUX1-089R, PRM-LUXl-090R, PRM-LUX-091R, PRM-LUX1-092R, and PRM-LUX-1-101) for the reasons described below.

Promotion of Unapproved New Use

Promotional materials are misleading if they suggest that a drug is useful in a broader range of patients or conditions than has been demonstrated by substantial evidence. Luxiq's approved product labeling (PI) states that "Luxiq is a medium potency topical corticosteroid indicated for relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses of the scalp."   In your promotional materials (PRM-LUX1-082R and PRM-LUXI-092R), you present that treatment with Luxiq is appropriate for patients such as a "58-year-old Caucasian male with 50-year history of erythematous, scaly, and pruritic eruption involving the scalp, elbows, and sacrum" and "45-year-old Caucasian female with an 8-year history of pruritic scaling and eruptions involving the elbows, knees, and scalp."   These claims are misleading because Luxiq is only indicated for dermatoses of the scalp.   Similarly, you present four of the case studies (PRM-LUX1-082R, PRM-LUXI-089R, PRM-LUX1090R, and PRM-LUXl-092R) with the header "Case Study: Psoriasis."  This implies that Luxiq is useful in patients with psoriasis on any part of the body when such has not been demonstrated by substantial evidence.

Overstatement of Efficacy

Luxiq's PI includes results from a clinical trial in 159 patients with moderate to severe scalp psoriasis demonstrating that Luxiq decreased scaling, erythema, and plaque thickness by 47%, 41 % and 66%, respectively.  In addition, according to the Investigator's Global assessment, 67% of patients treated with Luxiq were rated as completely clear or almost clear at endpoint.  In your promotional materials (PRM-LUX1-082R, PRM-LUX1-089R, PRM-LUX1-090R, PRM-LUX-091R, PRM-LUX1-092R, and PRM-LUX1-101), you present the following claims from each of the case studies:

The totality of these claims implies that all patients (as represented by 6 out of 6 patients described in each of the case studies) using Luxiq will have 90-100% clearance. Therefore, these claims are misleading because they are inconsistent with your PI and are an overstatement of the efficacy of Luxiq.

In addition, the trial described in the PI required that patients be treated twice daily for four weeks.  According to the PI, "At four weeks of treatment, study results of 159 patients demonstrated that the efficacy of Luxiq Foam in treating scalp psoriasis is superior to that of Placebo foam, and is comparable to that of a currently marketed BMV lotion."  However, your materials (PRM-LUX1-090R and PRM-LUX1-089R) include statements such as:

These statements are misleading because they are inconsistent with the PI and overstate the efficacy of Luxiq with respect to how long it takes to see results.

Superiority Claims

In describing the psoriasis case study of the 58-year-old male, your promotional material (PRMLUX1-082R) contains the statements under the header (prior treatments) that "Various topical corticosteroids that ranged from moderate to ultra-high potency have been used in the past" and "He has achieved variable and temporary relief from these prior therapies."   Furthermore, the case study states that the patient was treated with Luxiq twice daily for 2 weeks with the following outcome:  "As of 1 year after therapy, patient has not returned for additional treatment."   This presentation is misleading because it implies that Luxiq is superior to moderate and ultra-high potency corticosteroids when such has not been demonstrated by substantial evidence.   In addition, this presentation is misleading because it implies that Luxiq is a cure for psoriasis when such has not been demonstrated.

Requested Action

Connetics should immediately discontinue these and all other promotional materials and activities for Luxiq that contain the same or similar claims or presentations.  We request that Connetics respond, in writing, with its intent to comply with the above.  DDMAC should receive your written response no later than November 30, 2001.  This response should list similarly violative materials with a description of the method for discontinuation and the discontinuation date.

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, HFD42, Rm. 1713-20, 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 II) #10501 in addition to the NDA number.

Sincerely,

Barbara S. Chong, Pharm.D., BCPS 
Regulatory Review Officer 
Division of Drug Marketing, 
    Advertising and Communications