DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health ServiceFood and Drug AdministrationSilver Spring, MD 20993

TRANSMITTED BY FACSIMILE

Margaret J. JackDirector, DRAHoffmann-La Roche Inc., Bldg 1/2340 Kingsland StreetNutley, NJ 07110

RE: NDA #21-455, 21-858 BONIVA (ibandronate sodium) TabletsBLA #103964 PEGASYS (peginterferon alfa-2a) for InjectionNDA #20-896 XELODA (capecitabine) TabletsMACMIS ID #17318

Dear Ms. Jack:As part of its monitoring and surveillance program, the Division of Drug Marketing,Advertising, and Communications (DDMAC) of the U.S. Food and Drug Administration (FDA)has reviewed Hoffmann-La Roche Inc.’s (Hoffmann-La Roche) sponsored links on internetsearch engines (e.g., Google.com) for the following products: BONIVA (ibandronate sodium)Tablets (Boniva), PEGASYS (peginterferon alfa-2a) for Injection (Pegasys), and XELODA(capecitabine) Tablets (Xeloda). The sponsored links are misleading because they makerepresentations and/or suggestions about the efficacy of Boniva, Pegasys, and Xeloda, butfail to communicate

any

risk information associated with the use of these drugs. In addition,the sponsored links for Pegasys and Xeloda inadequately communicate the drugs’ indicationsand also fail to use the required established name. Thus, the sponsored links misbrand thedrugs in violation of the Federal Food, Drug, and Cosmetic Act (the Act) and FDAimplementing regulations.

See

21 U.S.C. 352(a) & (n), 321(n); 21 CFR 201.10(g)(1),202.1(b)(1), (e)(3)(i), (ii) & (e)(6)(i).

Background

Boniva

According to its FDA-approved product labeling (PI), Boniva is indicated for the treatment andprevention of osteoporosis in postmenopausal women. Boniva increases bone mineraldensity (BMD) and reduces the incidence of vertebral fractures.Boniva is associated with a number of risks, as reflected in the Contraindications, Warnings,Precautions, and Adverse Reactions sections of its PI.

Pegasys

According to its FDA-approved PI, Pegasys is indicated, among other things, alone or incombination with Copegus (ribavirin) for the treatment of adults with chronic hepatitis C(CHC) virus infection who have compensated liver disease and have not been previouslytreated with interferon alpha.

Margaret J. Jack Page

Hoffmann-La Roche Inc.NDA #21-455, 21-858, 20-896, BLA 103964MACMIS #17318

Pegasys is associated with a number of risks, as reflected in the Boxed Warning,Contraindications, Warnings, Precautions, and Adverse Reactions sections of its PI.

Xeloda

According to its FDA-approved PI, Xeloda is indicated, among other things, as a single agentfor adjuvant treatment in patients with Dukes’ C colon cancer who have undergone completeresection of the primary tumor when treatment with fluoropyrimidine therapy alone ispreferred. Xeloda was non-inferior to 5-flourouracil and leucovorin (5-FU/LV) for disease-freesurvival and while neither Xeloda nor combination therapy increases overall survival,combination therapy has been shown to improve disease-free survival compared to 5-FU/LV.Xeloda is also indicated as first-line treatment of patients with metastatic colorectal carcinomawhen treatment with fluoropyrimidine therapy alone is preferred. Combination chemotherapydemonstrated a survival benefit compared to 5-FU/LV alone, however, a survival benefit over 5-FU/LV has not been demonstrated with Xeloda monotherapyXeloda is associated with a number of risks, as reflected in the Boxed Warning,Contraindications, Warnings, Precautions, and Adverse Reactions sections of its PI.

Omission of Risk Information

Promotional materials, other than reminder pieces, which include the name of the drugproduct but do not include indications or other representations or suggestions relative to thedrug product (see 21 CFR 200.200, 201.100(f), 202.1(e)(2)(i)), are required to disclose riskand other information about the drug. Such materials are misleading if they fail to revealfacts that are material in light of the representations made by the materials or with respect toconsequences that may result from the use of the drug as recommended or suggested by thematerials. The sponsored links present the following claims:

•

Free Trial Offer www.Boniva.comBONIVA® (ibandronate sodium). Learn About PostmenopausalOsteoporosis.

•

PEGASYS® Official Sitewww.PEGASYS.comLearn About PEGASYS & Hepatitis C Register For The E-MailNewsletter.

•

XELODA® Informationwww.xeloda.comLearn About An Oral Chemotherapy Treatment For Colon Cancer.These sponsored links make representations and/or suggestions about the efficacy of Boniva, Pegasys, and Xeloda, respectively, but fail to communicate

any

risk information.This omission of risk information is particularly concerning as two of the products, Pegasysand Xeloda, have Boxed Warnings. For promotional materials to be truthful and non-misleading, they must contain risk information in each part as necessary to qualify any claimsmade about the drug.

Margaret J. Jack Page

Hoffmann-La Roche Inc.NDA #21-455, 21-858, 20-896, BLA 103964MACMIS #17318

By omitting the most serious and frequently occurring risks associated with the drugspromoted in the links above, the sponsored links misleadingly suggest that Boniva, Pegasysand Xeloda are safer than has been demonstrated. We note that these sponsored linkscontain a link to the products’ websites. However, this is insufficient to mitigate themisleading omission of risk information from these promotional materials.

Inadequate Communication of Indication

The sponsored links for Pegasys and Xeloda provide very brief statements about what thedrugs are for; however, these statements are incomplete and misleading, suggesting that thedrugs are useful in a broader range of conditions or patients than has been demonstrated bysubstantial evidence or substantial clinical experience.Specifically, the sponsored link for Pegasys misleadingly broadens the indication for Pegasysby implying that all patients with hepatitis C are candidates for Pegasys therapy (“LearnAbout PEGASYS & Hepatitis C…”), when this is not the case. Rather, Pegasys is onlyindicated (alone or in combination) for the treatment of chronic hepatitis C virus infection inadults who have compensated liver disease and who have not been treated with interferonalpha previously.Similarly, the sponsored link for Xeloda misleadingly broadens the indication for Xeloda byimplying that the drug is approved to treat any type of colon cancer (“Learn About An OralChemotherapy Treatment For Colon Cancer”), when this is not the case. Rather, Xeloda’sindication is limited to adjuvant treatment in patients with

Duke’s C colon cancer

and asfirst-line treatment for

metastatic colorectal carcinoma

. Furthermore, the sponsored linkfails to communicate any of the limitations to either of these indications or the drug’s limitedproven survival benefits.

Failure to Use Required Established Name

The sponsored links for Pegasys and Xeloda fail to present the full established name of thedrugs being promoted, despite the requirement to do so.

See

21 CFR 201.10(g)(1) &202.1(b)(1).

Conclusions and Requested Action

For the reasons discussed above, the sponsored links misbrand Boniva, Pegasys andXeloda, in violation of the Act and FDA regulations.

See

21 U.S.C. 352(a) & (n), 321(n); 21CFR 201.10(g)(1), 202.1(b)(1), (e)(3)(i), (ii) & (e)(6)(i).DDMAC requests that Hoffmann-La Roche immediately cease the dissemination of violativepromotional materials for Boniva, Pegasys and Xeloda, such as those described above.Please submit a written response to this letter on or before April 9, 2009, stating whether youintend to comply with this request, listing all promotional materials (with the 2253 submissiondate) in use for these drugs as of the date of this letter, identifying which of these materialscontain violations such as those described above, and explaining your plan for discontinuinguse of such materials. Finally, we encourage you to review your promotional materials for the