FDA Approves First Drug for Treatment of Chorea in Huntington's

Susan Jeffrey

August 15, 2008

August 15, 2008 — The US Food and Drug Administration (FDA) has announced approval of tetrabenazine (Xenazine, Prestwick Pharmaceuticals) for the treatment of chorea in Huntington's disease. The drug is the first agent of any kind approved in the United States for any symptom of Huntington's disease, the FDA notes in a press statement issued today.

"Xenazine represents hope for patients and families dealing with this difficult disease," Timothy Coté, MD, director of the FDA's Office of Orphan Products Development, said in the FDA statement. "For the first time, there is a treatment that can help patients with this disease gain some quality of life."

Serious adverse effects have been reported with use of tetrabenazine, the FDA notes, including depression and suicidal thoughts and actions, so the drug should not be used in patients who are actively suicidal or in those with untreated depression.

According to information from the drug's manufacturer, tetrabenazine is a highly selective and reversible centrally acting dopamine-depleting drug, and it works by inhibiting a molecule called vesicular monoamine transporter 2 (VMAT2).

Tetrabenazine was granted orphan drug designation by the FDA; a drug is granted orphan status if it addresses a population of fewer than 200,000 patients or if it treats conditions that affect more than 200,000 patients but where there is no reasonable expectation of profit being recovered for the drug. About 30,000 people in the United States have Huntington's disease, and another 200,000 are at risk of developing the disease, the FDA statement notes.

The drug was reviewed by the FDA's peripheral and central nervous system drugs advisory committee on December 6, 2007, which voted unanimously for approval of tetrabenazine in this indication.

A randomized trial of the effectiveness and safety of tetrabenazine showed that the drug was effective in lessening chorea, according to the FDA (Huntington Study Group. Neurology. 2006;66:366-372. The study was funded by Prestwick Pharmaceuticals). Adverse effects seen in that and other clinical trials included insomnia, depression, drowsiness, restlessness, and nausea.

Clinical trials also showed a slight worsening in mood, cognition, rigidity, and functional capacity, the release adds. "Healthcare professionals and family members of patients taking the drug should pay attention to all of the facets of the disease," the FDA release notes.

The drug has been approved with a required risk evaluation and mitigation strategy (REMS), to ensure that the benefits of the drug outweigh its risks, particularly depression and suicidal thoughts and actions. The REMS includes educational materials for prescribers and pharmacists as well as for patients and caregivers to help minimize adverse effects with the drug, the FDA release points out.

The REMS also includes a medication guide that informs patients and their caregivers about the risks for depression, suicidal thoughts and actions, and adverse effects. The FDA requires that the guide be handed out with every prescription for the drug that is dispensed.

Asked for comment on the potential impact of this drug, Stanley Fahn, MD, from the Neurological Institute at Columbia University in New York, said that he has been using tetrabenazine for almost 40 years, importing it under an Investigational new drug (IND) application from the FDA. He participated in the Huntington Study Group trial on which the approval was based.

"We have a lot of experience with the drug, and we're very happy that the rest of the population will be able to use this drug as well," Dr. Fahn told Medscape Neurology & Neurosurgery. Although the company has focused its efforts to get approval for the drug for the chorea of Huntington's disease under the orphan drug program, he and others also use tetrabenazine for chorea associated with other neurological diseases such as tardive dyskinesia.

Adverse effects with the drug, including depression, parkinsonism, and akathisia, are common, he noted, but in general these are dose dependent and readily reversible. "The idea would be just to keep the doses at a very low level and monitor the patient for these side effects, warning patients about them in advance. If you observe them, you can reduce the drug or, if necessary, eliminate it," he said.

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