Teva Neuroscience, Inc. — AUSTEDO® XR (deutetrabenazine) extended-release tablets, for oral use (2025-09-09)

DEPARTMENT OF HEALTH & HUMAN SERVICES Public Health Service

Food and Drug Administration Silver Spring, MD 20993

Thomas Kenney Director, Regulatory Affairs

145 Brandywine Parkway, Building 300 West Chester, PA 19380

RE: NDA 216354 ® AUSTEDO XR (deutetrabenazine) extended-release tablets, for oral use MA 342

Dear Thomas Kenney:

The U.S. Food and Drug Administration (FDA) has reviewed the promotional communications, two direct-to-consumer broadcast advertisements (TV ads), titled “Daughter ® Knows Best” (AUS-47657) and “Spouse Knows Best” (AUS-47658), for AUSTEDO XR (deutetrabenazine) extended-release tablets (Austedo XR), submitted by Teva Neuroscience Inc. (Teva) under cover of Form FDA 2253. FDA has determined that the TV ads are false or misleading. Thus, the TV ads misbrand Austedo XR and make the distribution of the drug in violation of the Federal Food, Drug, and Cosmetic Act (FD&C Act).

The TV ads begin with each protagonist, a mother and a spouse, showing obvious uncontrollable movements, indicative of tardive dyskinesia (TD). The TV ads emphasize how uncontrollable movements in the mouth and eyes may affect an individual with TD and be noticed by a TD patient’s family member. Each protagonist is shown interacting with their respective family member, who notes the mouth and eye movements. Austedo XR is then introduced. The TV ads then have lengthy post-treatment segments in which the protagonists go through their daily activities without showing involuntary movements that are easily noticed by the viewer. The mother is shown interacting with her daughter, pouring a cup of coffee, zipping a purse, putting on an earring, and eating a meal with friends. The spouse is shown pouring a cup of hot tea, zipping a vest, unclipping a grill cover, hanging outdoor string lights, and interacting with friends at a backyard barbecue. During each TV ad, the protagonist carries a bright orange travel mug in a perfectly steady manner, which gives the misleading impression that treatment with Austedo XR will result in constant hand steadiness without any noticeable involuntary body movements.

These presentations misleadingly suggest that Austedo XR provides a greater magnitude of benefit in the treatment of TD than has been demonstrated. According to the CLINICAL STUDIES section of the FDA-approved prescribing information (PI), approval of Austedo XR relied on two studies supporting the use of Austedo in the treatment of TD. The primary endpoint of these studies was the change from baseline in the Abnormal Involuntary

Movement Scale (AIMS) total score at week 12. The mean AIMS total score in all treatment and placebo groups ranged from 9.4 to 10.1 at baseline. Table 6 in the PI shows that the change from baseline to week 12 in Study 1 was approximately -1.9 relative to placebo (i.e., -3.3 and -3.2 units for the Austedo 36 mg and 24 mg arms, respectively, compared with -1.4 units for placebo). In Study 2, the change from baseline was approximately -1.4 relative to placebo (i.e., -3.0 units for Austedo, compared with -1.6 units for placebo). These results do not correlate with the near-complete resolution of symptoms portrayed in the post- treatment portion of these TV ads. FDA acknowledges that both TV ads include the SUPER, “Individual results may vary.” Furthermore, we acknowledge that the TV ads also include the SUPER, “In one study, patients taking AUSTEDO 36 mg saw a 33% movement improvement vs 14% for placebo at 12 weeks.” However, neither presentation mitigates the misleading impression that patients can expect a near-complete resolution of TD symptoms when taking Austedo XR.

Conclusion and Requested Action

For the reasons described above, the TV ads misbrand Austedo XR and make the distribution of the drug in violation of the FD&C Act.

This letter notifies you of our concerns and provides you with an opportunity to address them. FDA requests that Teva 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 Austedo XR that contain representations like those described above, and explaining your plan for the discontinuation of such communications, or for ceasing distribution of Austedo XR.

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.

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 342 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

The AIMS is a 12-item clinician-rated scale; items 1 to 7 assess the severity of involuntary movements across body regions, and these items were used in the studies. The AIMS total score (sum of items 1 to 7) can range from 0 to 28, with a score of 0 representing no involuntary movements and 28 representing severe involuntary movements in all body regions assessed.

submission should be coded as an Amendment to eCTD Sequence 0402 under NDA 216354. 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 05:17:34 PM On behalf of George Tidmarsh, M.D., Ph.D