Michelle H. Rohrer, Ph.D.
Vice President, Regulatory Affairs
Genentech, Inc.
1 DNA Way
South San Francisco, CA 94080-4990

RE: NDA #021455
      BONIVA (ibandronate sodium) Tablets
      MACMIS #19409

Dear Dr. Rohrer:

The Division of Drug Marketing, Advertising, and Communications (DDMAC) of the U.S. Food and Drug Administration (FDA) has reviewed Genentech, Inc.’s (Genentech) Sally #6 Print Page & 1/3 (9893500) (print ad) for BONIVA (ibandronate sodium) Tablets (Boniva) which

ran in the December 12, 2010, issue of Parade magazine. The print ad is misleading because it overstates the efficacy of Boniva. Thus, the print ad misbrands Boniva in violation of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. 352(n) and FDA implementing regulations. 21 CFR 202.1(e)(6)(i) & (e)(7)(iii).

Background

According to its FDA-approved product labeling (PI), Boniva is indicated for the treatment and prevention of osteoporosis in postmenopausal women.

According to the Clinical Studies – Treatment of Postmenopausal Osteoporosis – Once- Monthly Dosing section of the PI, the efficacy and safety of once-monthly Boniva were demonstrated in a randomized, double-blind, multinational, non-inferiority trial in 1602 women aged 54 to 81 years, who were on average 18 years post-menopause, and had 1-2-1-4 lumbar spine bone mineral density (BMD) T-score below -2.5 standard deviations at baseline. The main outcome measure was the comparison of the percentage change from baseline in lumbar spine BMD after 1 year of treatment with once-monthly ibandronate (100 mg, 150 mg) to daily ibandronate (2.5 mg). Boniva 150 mg once-monthly was shown to be non-inferior to Boniva 2.5 mg daily in lumbar spine BMD.

Overstatement of Efficacy

Promotional materials are misleading if they represent or suggest that a drug is more effective than has been demonstrated by substantial evidence or substantial clinical experience.

The print ad includes the following claim:

• “. . . Now, once-monthly BONIVA is helping me do more. Studies show, after a year on BON IVA, 9 out of 10 women stopped and reversed their bone loss.^†
†Bone density measured at the lumbar spine, total hip, or trochanter; 3 out of 4 at the femoral neck.”

This claim misleadingly overstates the efficacy of Boniva because it suggests that treatment with Boniva will result in 9 out of 10 women stopping and reversing their bone loss when this is not supported by substantial evidence or substantial clinical experience. This claim is based on a per-protocol post-hoc analysis of a secondary efficacy endpoint of the percentage of responders (defined as BMD being equal to or above baseline at one year) at the lumbar spine, total hip, trochanter, and femoral neck. However, the clinical study that served as the basis for approval of once-monthly Boniva for the treatment of postmenopausal osteoporosis was designed to assess the percent change from baseline in lumbar spine BMD at 1 year. Thus, this claim is based on a post-hoc responder analysis that the clinical study was not adequately designed to evaluate. Therefore, claims suggesting that 90% of women will stop and reverse their bone loss with Boniva therapy misleadingly overstate the efficacy of the drug and are not supported by substantial evidence.

Conclusion and Requested Action

For the reasons discussed above, the print ad misbrands Boniva in violation of the Act 21 U.S.C. 352(n) and FDA implementing regulations. 21 CFR 202.1(e)(6)(i) & (e)(7)(iii).

DDMAC acknowledges that Genentech has initiated procedures to cease the dissemination of violative promotional materials for Boniva, such as those described above. Please submit a written response to this letter on or before January 21, 2011, confirming your receipt of this letter, providing a complete listing of all promotional materials (with 2253 submission date) for Boniva that contain violations such as those described above, and reaffirming your plans to immediately cease dissemination of the violative promotional materials. Please direct your response to me at the Food and Drug Administration, Center for Drug Evaluation and Research, Division of Drug Marketing, Advertising, and Communications, 5901-B Ammendale Road, Beltsville, MD 20705-1266, facsimile at 301-847-8444. In all future correspondence regarding this matter, please refer to MACMIS #19409 in addition to the NDA number. We remind you that only written communications are considered official.

The violations discussed in this letter do not necessarily constitute an exhaustive list. It is your responsibility to ensure that your promotional materials for Boniva comply with each applicable requirement of the Act and FDA implementing regulations.

Sincerely,

Michelle Safarik, MSPAS, PA-C
Regulatory Review Officer
Division of Drug Marketing,
Advertising, and Communications