First Drug Approved in US for Huntington's Chorea
Despite the discovery in 1993 of the altered gene that causes Huntington's disease (HD), treatment for this dismal illness remains purely symptomatic and supportive. In the United States, medical therapy for HD chorea has been limited to traditional dopamine-receptor-blocking neuroleptics; however, these medications are associated with a high incidence of extrapyramidal side effects (eg, Parkinsonism) and irreversible tardive dyskinesia.
On Friday, the FDA approved tetrabenazine (Xenazine; Prestwick Pharmaceuticals), a well-known dopamine-depleting agent, for the treatment of HD chorea. The drug, which was granted "orphan drug status," is the first medication approved in the United States for the movement disorder; although tetrabenazine has been in use for HD chorea in Canada, Europe, and other parts of the world. The agent, which probably has limited dopamine-receptor-blocking properties at therapeutic dosages, has not been associated with the development of tardive dyskinesia.
Tetrabenazine was approved for HD chorea on the basis of a multicenter, prospective, double-blind, placebo-controlled study of ambulatory patients with HD (N = 84). Randomly assigned tetrabenazine* was associated with a 3.5-unit relative reduction of the chorea score (Unified HD Rating Scale) at 12 weeks. Five tetrabenazine-treated patients withdrew from the study, and 5 serious adverse events—drowning suicide, complicated fall, restlessness/suicidal ideation, and breast cancer—were reported with treatment. Nevertheless, another controlled study (industry sponsored) and open-label studies support the drug's use in HD.
With the approval of tetrabenazine, the FDA requires a company-supplied Risk Evaluation and Mitigation Strategy (REMS) to manage any serious risks associated with the drug.
* Titrated up to a maximum of dosage of 100 mg/d.
Public-domain photo of American folk legend Woody Guthrie, who died of complications due to HD in 1967.
