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In Pursuit of Tardive Dyskinesia: The Breakthrough Designation and Approval of Valbenazine

Spotlight on CDER Science

Brian J. Miller, M.D., M.B.A., M.P.H., Michael C. Davis, M.D., Ph.D., and Mitchell V. Mathis, M.D., Division of Psychiatry Products, Office of New Drugs, Center for Drug Evaluation and Research

Diseases that are caused by medical treatments and procedures are a particular bane to health care providers. One such example is tardive dyskinesia, a side effect of taking antipsychotic medicines. Tardive dyskinesia is a neurological disorder characterized by repetitive, involuntary movements such as lip smacking or pursing, as well as tongue movements. Tardive dyskinesia significantly impacts the health and quality of life of many people who live with psychiatric illnesses, and the disorder is often irreversible. The FDA approval of valbenazine this year, the first drug to be indicated for tardive dyskinesia, is therefore noteworthy—not only because it addresses an unmet need, but also because of how it was approved.


In the 1950s, first-generation antipsychotics, such as chlorpromazine and haloperidol, revolutionized psychiatric care by offering unprecedented relief from the symptoms of psychosis. Antipsychotic drugs work to regulate the action of dopamine, a chemical that carries nerve signals in specialized areas of the brain. Within the first years of their use, it became apparent that these new drugs caused tardive dyskinesia in some patients. In subsequent decades, second-generation antipsychotics (or “atypicals”) were introduced, but these also proved to cause tardive dyskinesia, although to a lesser extent. Scientists suspect that antipsychotic drugs cause irregular dopamine signaling, which can lead to the development of tardive dyskinesia.
Researchers have studied a number of possible treatments for tardive dyskinesia, including vitamins and many different medicines. One medication, tetrabenazine, which is approved to treat involuntary movements associated with Huntington’s disease, showed promise for the treatment of tardive dyskinesia in small studies. (In fact, after valbenazine received FDA approval this year, a heavy form of tetrabenazine, known as deutetrabenazine, was also approved for tardive dyskinesia.) Valbenazine has similar effects in the brain as tetrabenazine. Therefore, there was interest in studying valbenazine for tardive dyskinesia caused by antipsychotic drugs.

A Breakthrough Therapy

In October 2014, after extensive discussions with the drug’s sponsor (Neurocrine Biosciences) and promising results from studies of valbenazine for tardive dyskinesia, FDA designated valbenazine as a breakthrough therapy. The FDA’s breakthrough pathway supports the agency’s initiatives to enhance drug review flexibility and transparency. In the case of valbenazine, the breakthrough designation facilitated discussions between the FDA and the drug sponsor, which in combination with a priority review of valbenazine led to drug approval eight months after the sponsor submitted the new drug application.

The story of valbenazine reflects the significance of effective collaboration between drug developers and regulators to benefit patients in need. The FDA has committed itself to leveraging flexibility, transparency, and collaboration on behalf of American patients. Advances in regulatory science and review practices, such as the breakthrough and priority review pathways, reflect this commitment.


Davis, MC, Miller, BJ, Kalsi, JK, Birkner, T, and Mathis, MV. Efficient trial design—FDA approval of valbenazine for tardive dyskinesia. New Engl J Med 2017 May 10. 

The Spotlight series presents generalized perspectives on ongoing research and science-based activities within CDER. Spotlight articles should not be construed to represent FDA’s views or policies.

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