Released by FDA: 5/9/00.  Posted by FDA:  5/22/00

C. Elaine Jones, Ph.D. 
Product Director, Regulatory Affairs 
Glaxo Wellcome Inc. 
5 Moore Drive 
P.O. Box 13398 
Research Triangle Park, NC 27709

Re:   NDA# 20-548 
        Flovent (fluticasone propionate) Inhalation Aerosol 
            44 mcg, 110 mcg, 220 mcg 
        MACMIS ID#: 8868

Dear Dr. Jones:

This letter concerns professional and direct-to-consumer promotional materials and advertisements for Flovent (fluticasone propionate) 44 mcg and 110 mcg Inhalation Aerosol disseminated by Glaxo Wellcome Inc (GW) (e.g., pharmacist letter FLO67RO, April 2000).  The Division of Drug Marketing, Advertising, and Communications (DDMAC) has reviewed these pieces and concluded that GW is disseminating promotional materials that contain a misleading clinical superiority claim. This claim violates the Federal Food, Drug, and Cosmetic Act and implementing regulations and should be discontinued immediately.

These presentations suggest that asthma patients who are being treated with inhaled corticosteroids (ICSs), including any out-of-stock beclomethasone dipropionate (BDP) inhalation aerosol product (i.e., Vanceril 42 mcg or 84 mcg Inhalation Aerosol), should consider being switched to Flovent because, among other reasons, it is “the number one prescribed (branded)¹  inhaled anti-inflammatory asthma medication in the world” and because “Flovent has been proven superior to Beclovent (beclomethasone dipropionate) Inhalation Aerosol in improving lung function by FEV₁²”

The Beclovent comparison is a misleading global clinical superiority claim and suggests that Flovent is the best ICS choice for asthma controller therapy.  However, it is misleading to suggest that Flovent is superior to all BDP products based on data comparing only Beclovent brand BDP Inhalation Aerosol at 42 mcg per puff because other BDP products vary by formulation and dosage strength.  Moreover, it misleading to suggest that Flovent is superior to Beclovent regardless of how each product is dosed.  The study trials did not demonstrate that Flovent was more efficacious than Beclovent on a microgram-versus-microgram basis for measuring FEV₁.  There was no consistent replication of the superiority of the individual doses of Flovent against the individual doses of Beclovent, nor did the trials demonstrate that Flovent had superior “lung function” based on secondary efficacy endpoints (PEFRs and PVC).  Therefore, the suggestion of Flovent’s global superior efficacy is unsubstantiated and misleading.

Furthermore, this global “proven superior” claim suggests a better therapeutic ratio for Flovent compared to Beclovent by making inferences about relative safety.  However, the trials did not measure systemic safety (e.g., HPA-axis suppression) between Flovent and Beclovent.  Without valid comparative systemic safety assessments, it is misleading to suggest a superior safety profile between these products based only on adverse events.  Therefore, the suggestion of global superiority based on Flovent’s better benefit-to-risk ratio is unsubstantiated and misleading.

On April 29 and June 9, 1998, DDMAC raised each of these issues to GW in written comments on a preliminarily proposed Flovent presentation that were based in part on these study data.

GW should immediately cease its dissemination and use of all promotional materials for Flovent with this misleading global superiority claim.  We should receive your written response no later than May 23, 2000, and it should list all similarly violative materials, with a description of your method of discontinuation.  Your response should be directed to the undersigned by facsimile at (301) 594-6771, or at the Food and Drug Administration, Division of Drug Marketing, Advertising and Communications, HFD-42, Rm 17-B-20, 5600 Fishers Lane, Rockville, Maryland 20857.  We remind GW that only written communications are considered official.

In future correspondence regarding this particular matter, please refer to MACMIS ID# 8868 in addition to the NDA number.

Sincerely, 

Joan Hankin, JD 
Regulatory Review Officer 
Division of Drug Marketing, 
   Advertising and Communications

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¹   Those promotional materials that Omit the qualifier “brand” in the “most prescribed” claim are misleading. 

²   Raphael GD, Lanier RQ, Baker J, et al.   A comparison of multiple doses of fluticasone propionate and beclomethasone dipropionate in subjects with persistent asthma.”  J Allergy Clin Immunol. 1999;103:796-803.