Novartis Pharmaceuticals Corporation — KISQALI® (ribociclib) tablets, for oral use (2025-09-09)

DEPARTMENT OF HEALTH & HUMAN SERVICES Public Health Service

Food and Drug Administration Silver Spring, MD 20993 Bob Bedolla Director, Regulatory Affairs, Advertising and Promotion Review

One Health Plaza East Hanover, NJ 07936-1080

RE: NDA 209092 ® KISQALI (ribociclib) tablets, for oral use MA 1975

Dear Bob Bedolla:

The U.S. Food and Drug Administration (FDA) has reviewed the promotional communication(s), DTC broadcast advertisement (TV ad) “KISQALI_mBC_OKE_Jordan 60 ® Second Major Statement Update_US_2.25” for KISQALI (ribociclib) tablets, for oral use (Kisqali) submitted by Novartis Pharmaceuticals Corporation (Novartis) under cover of Form FDA 2253. FDA has determined that the TV ad is false or misleading. Thus, the TV ad misbrands Kisqali and makes the distribution of the drug in violation of the Federal Food, Drug, and Cosmetic Act (FD&C Act).

The TV ad includes the following claims:

• Voice over (VO) frames 7-9: “. . .Then I learned about KISQALI. . .a pill that stops cancer from growing. . .and can help me live longer.”

• Voice over (VO) frame 13: “KISQALI with an aromatase inhibitor is for adults with HR- positive, HER2-negative metastatic breast cancer.”

• Superimposed text (SUPER) frame 13: “Postmenopausal women taking KISQALI plus an NSAI lived for 63.9 months vs 51.4 months on an NSAI alone. Premenopausal women taking KISQALI with an NSAI and goserelin lived for 58.7 months vs 47.7 months on an NSAI and goserelin alone.”

The claim, “Premenopausal women taking KISQALI with an NSAI and goserelin lived for 58.7 months vs 47.7 months on an NSAI and goserelin alone” presented in the SUPER on frame 13 reflects overall survival (OS) data from an extended exploratory analysis. This claim creates a misleading impression about the efficacy of the drug. According to the CLINICAL STUDIES section of the Kisqali PI, a statistically significant OS benefit was demonstrated in premenopausal women with Kisqali with an NSAI and goserelin compared to an NSAI and

Lu YS, Im SA, Colleoni M, et al; 2022. Updated Overall Survival of Ribociclib plus Endocrine Therapy versus Endocrine Therapy Alone in Pre- and Perimenopausal Patients with HR+/HER2- Advanced Breast Cancer in MONALEESA-7: A Phase III Randomized Clinical Trial. Clin Cancer Res; 28(5):851-859.

goserelin alone, with a median OS that was not reached in the Kisqali arm versus 40.7 months in the comparator arm (HR=0.699 [95% CI: 0.501, 0.976]). These results were considered final per the study protocol. However, the OS results for premenopausal women presented on frame 13 are from a 54-month extended exploratory analysis, which was not pre-specified and is observational in nature. As such, there was no pre-specified statistical procedure controlling for type 1 error; therefore, it is not possible to exclude that the results are skewed given the lack of pre-specified alpha allocation. An unplanned, exploratory collection of overall survival data can lead to imbalanced censoring or early censoring between arms, causing the resulting estimates to be unreliable. Additionally, the exploratory analysis of OS for Kisqali is based on a collection of datapoints across the entire Kaplan- Meier (KM) curve, rather than a specific time point, and it is necessary to consider the entirety of the KM curve in order to accurately interpret this claim. The context regarding the limitations of the exploratory analysis and the full KM curve are necessary to accurately interpret the above cited claim.

Additionally, the SUPER on frame 13 that includes the material information for the claim “KISQALI . . . can help me live longer” presents 40 words in approximately 6 seconds, which translates to a reading speed of 400 words per minute (wpm). A review and meta-analysis found that the average silent reading rate for adults in English is 238 wpm for uninterrupted non-fiction reading, with most adults falling in a range of 175 to 300 wpm. Moreover, during the 6-second period that the SUPER appears, there are multiple competing audio presentations. The audio states, “KISQALI with an aromatase inhibitor is for adults with HR- positive, HER2-negative metastatic breast cancer” while music with lyrics plays in the background. Overall, by presenting competing modalities during the presentation of the SUPER, which itself is presented in a manner that would not allow most viewers to read, process, and comprehend the material information it presents, the TV ad misleadingly undermines the communication of material information about the drug’s efficacy.

Conclusion and Requested Action

For the reasons described above, the TV ad misbrands Kisqali and makes the distribution of the drug in violation of the Federal Food, Drug, and Cosmetic Act (FD&C Act).

This letter notifies you of our concerns and provides you with an opportunity to address them. FDA requests that Novartis take immediate action to address any violations (including, for example, ceasing and desisting promotional communications that are misleading as described above). Please submit a written response to this letter within 15 working days from the date of receipt, addressing the concerns described in this letter, listing all promotional communications (with the 2253 submission date) for Kisqali that contain representations like those described above, and explaining your plan for the discontinuation of such communications, or for ceasing distribution of Kisqali.

If you believe that your products are not in violation of the FD&C Act, please include in your submission to us your reasoning and any supporting information for our consideration within 15 working days from the date of receipt of this letter.

Brysbaert, Marc. (2019). How many words do we read per minute? A review and meta-analysis of reading rate. 10.31234/osf.io/xynwg.

The concerns discussed in this letter do not necessarily constitute an exhaustive list of potential violations. It is your responsibility to ensure compliance with each applicable requirement of the FD&C Act and FDA implementing regulations.

Please direct your response to the Food and Drug Administration, Center for Drug Evaluation and Research, Office of Prescription Drug Promotion, 5901-B Ammendale Road, Beltsville, Maryland 20705-1266 . A courtesy copy can be sent by facsimile to (301) 847-8444. Please refer to MA 1975 in addition to the NDA number in all future correspondence relating to this particular matter. All correspondence should include a subject line that clearly identifies the submission as a Response to Untitled Letter. You are encouraged, but not required, to submit your response in eCTD format. All correspondence submitted in response to this letter should be placed under eCTD Heading 1.15.1.6. Additionally, the response submission should be coded as an Amendment to eCTD Sequence 7496 under NDA 209092. Questions related to the submission of your response letter should be emailed to CDER-OPDP-RPM@fda.hhs.gov .

Sincerely,

{See appended electronic signature page}

George Tidmarsh, M.D., Ph.D. Director Center for Drug Evaluation and Research

Signature Page 1 of 1 -------------------------------------------------------------------------------------------- This is a representation of an electronic record that was signed electronically. Following this are manifestations of any and all electronic signatures for this electronic record. -------------------------------------------------------------------------------------------- /s/ ------------------------------------------------------------

CARTER M BEACH 09/09/2025 05:15:15 PM On behalf of George Tidmarsh, M.D., Ph.D