Released by FDA: 6/9/00.  Posted by FDA:  6/29/00

Debra Hackett 
Assistant Director 
U.S. Regulatory Affairs 
SmithKline Beecham Phannaceuticals 
One Franklin Plaza, P.O. Box 7929 
Philadelphia, PA 19101-7929

RE:    NDA 20-363 
         Famvir (famciclovir) 
         MACMIS ID#9032

Dear Ms. Hackett:

This letter concerns SmithKline Beecham Pharmaceuticals’ (SB) promotional materials for Famvir.  The Division of Drug Marketing, Advertising, and Communications (DDMAC) has reviewed these promotional materials as part of its routine monitoring and surveillance program.  From its review, DDMAC has concluded that SB has distributed materials that are false or misleading, in violation of the Federal Food, Drug, and Cosmetic Act (Act) and its implementing regulations.

In promotional pieces,¹ you have presented misleading safety and efficacy claims, and unsupported superiority claims regarding Famvir, in violation of the Act.

Misleading Safety Claims 

In your brochure, FV0720, you misleadingly claim, “Adverse events for HIV-infected patients were comparable to those seen in immunocompetent patients” and “Well tolerated by HIV-infected patients, with adverse events similar to otherwise healthy adults.”  These statements are misleading because you have not demonstrated by substantial evidence that adverse events for HIV-infected patients were comparable to either “immunocompetent patients” or “otherwise healthy adults.”  According to the approved product labeling (P1), a randomized, double-blind study compared Famvir with oral acyclovir in HIV-infected patients with recurrent mucocutaneous herpes simplex infection.  The comparator arms studied in this trial did not include “immunocompetent patients” or “otherwise healthy adults.”

Furthermore, in your brochure under the heading “Generally well tolerated,” you present the statement, “Famvir has been prescribed over 4 million times worldwide.” This presentation misleadingly implies that safety has been established in a larger number of patients than has been demonstrated by substantial evidence.  The total number of prescriptions derived from IMS data does not support claims of safety or efficacy for Famvir.

Misleading Efficacy Claims 

In promotional pieces, FV3306 and FV0720, you prominently present efficacy claims such as “Reduce genital herpes outbreaks by 80% with FAMVIR,” “Reduce genital herpes outbreaks with FAMVIR,” “Reduce genital herpes outbreaks by 80% with continuous FAMVIR therapy,” and “Proven to reduce recurrences by 80%.”   In addition, you present bar graphs of the median number of outbreaks in one year for Famvir and placebo as 1 vs. 5 outbreaks, respectively.   These claims and presentation misrepresent clinical trial results, implying that Famvir is more effective than demonstrated by substantial evidence.  For example, the claim that Famvir reduces recurrences by “80%” overstates recurrence-free rates of 29% for Famvir vs. 6% for placebo and recurrence rates of 53% for Famvir vs. 78% for placebo at one year.

Unsupported Superiority Claims

 In your brochure, FV0720, under the heading, “For Suppressive Treatment of OH,” you misleadingly claim, “Multidosing is more effective than once-daily dosing in preventing recurrences during long-term suppressive therapy.”  This statement misleadingly implies that the recommended twice daily dosing for Famvir is more effective than the recommended once-daily dosing of another approved antiviral product for suppressive treatment of genital herpes when such has not been demonstrated by substantial evidence (i.e., adequate and well-controlled head-to-head comparative trials).

In promotional pieces, FV3306 and FV0720, you claim, “Famvir lasts longer in infected cells than acyclovir,” and numerically present bar graphs of the half-life activity within HSV-2 infected cells (in vitro), 20 hrs. vs. 1 hr. for Famvir and acyclovir, respectively.  In addition, you present similar half-life comparisons for HSV-l and VZV infected cells in brochure, FV0720. In FV 3306, you also present the statements, “Famciclovir is converted to the active agent penciclovir triphosphate. Valacyclovir hydrochloride is converted to acyclovir.”  This presentation is misleading because it implies clinical significance and suggests that Famvir is superior to valacyclovir hydrochloride or acyclovir because of its longer half-life when such has not been demonstrated by substantial evidence.  We note the small font disclaimers, “During an active infection, the dosing of Famvir may be due to its long intracellular half-life” and “The clinical sig,uficance is unknown;” however, they are neither sufficient nor prominent to overcome the overall misleading suggestion of clinical significance and superiority.

REQUESTED ACTIONS

SB should immediately cease publication or dissemination of promotional materials that contain these or similar claims.  In addition, SB should respond in writing no later June 23, 2000, describing its plan to comply.  SB should also include a list of all similarly violative materials being discontinued, as well as the date of discontinuation.

Your response should be directed to the undersigned by fax at (301) 594-6771, or at the Food and Drug Administration, Division of Drug Marketing, Advertising and Communications, HFD-42, 17B-20, 5600 Fishers Lane, Rockville, MD 20857. DDMAC reminds SB that only written communications are considered official.

In all future correspondence regarding this particular matter, please refer to MACMIS ID #9032 in addition to NDA 20-363.

Sincerely,

Ele Ibarra-Pratt, R.N., M.P.H. 
Regulatory Review Officer 
Division of Drug Marketing, 
   Advertising and Communications

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¹ FV3306 (sales aid) and FV0720 (brochure)