The US Food and Drug Administration (FDA) announced on Friday that it has approved Prestwick Pharmaceuticals Inc’s new drug Xenazine (generic name tetrabenazine) for the treatment of chorea in people with Huntington’s disease, heralding the first treatment to receive US approval for any of the disease’s symptoms.

Huntington’s is a rare inherited neurological disorder characterized by chorea or jerky, uncontrolled movements. It affects about 1 in 10,000 people in the US where about 30,000 people are living with the disease and another 200,000 are at risk of developing it. The disease is caused by brain cell degeneration that is switched on by a mutated gene. A child has a 50 per cent chance of getting the disease from a biological parent.

Huntington’s disease also causes people to lose their intellectual faculties and to become emotionally disturbed, and symptoms usually develop between the ages 30 and 50. People can live for another 15 to 20 years after onset because the disease progresses slowly.

Director of FDA’s Office of Orphan Products Development, Dr Timothy Coté, said in a press statement that for the first time Huntington’s patients will be able to gain some quality of life through treatment. He said:

“Xenazine represents hope for patients and families dealing with this difficult disease.”

Orphan products is a category of drugs that is given special priority and exclusivity under federal laws, without which companies would not be prepared to invest the funds to develop drugs for people with very rare diseases. Orphan status applies to disease that affect less than 200,000 people in the US. Drugs for diseases that affect more than this number of people can also receive orphan status if there is no reasonable expectation that the development cost will be recovered from sales of the drug.

Xenazine reduces the amount of dopamine around certain synapses, the junctions through which brain cells communicate with each other using dopamine as a chemical messenger. People with Huntington’s have too much dopamine around certain types of brain cells, which leads to chorea, the jerkiness of movement.

The drug was tested in a randomized, double-blind, placebo-controlled multi-center clinical trial. Double blind means neither the patients nor the doctors knew if they were using the real drug or a placebo. Other studies supported the evidence of the trial, said the FDA.

Serious adverse reactions reported from trial use included depression and suicidal thoughts and behaviour, so the FDA advises that doctors should not use Xenazine with patients who have untreated depression or who are actively suicidal. Risk of suicide is a heightened concern when treating patients with Huntington’s.

Other common side effects reported by patients in the trial include: insomnia, depression, drowsiness, restlessness and nausea. Also, although the trials showed the drug lessens chorea in the short term, it also caused worsening of mood, cognition, rigidity and functional capacity, so the FDA advises doctors and families of patients on the drug to pay attention to all the aspects of the disease.

The FDA has approved Xenazine with a required Risk Evaluation and Mitigation Strategy (REMS) to ensure everything is done to make the benefits outweight the risks, and especially the risks of depression and suicidal thoughts and behaviours. The REMS Medication Guide, which has to be handed out with each prescription, describes for patients and caregivers the risks of depression and suicidal behaviour, and other side effects.

Dr Nancy Wexler, Higgins Professor of Neuropsychology in the departments of neurology and psychiatry at Columbia University and president of the Hereditary Disease Foundation, said:

“We are ecstatic that, through the approval of Xenazine, patients and families will have the option to take the only drug developed specifically for treating the movements of Huntington’s disease.”

“Chorea is a major cause of disability and death in patients with Huntington’s disease,” explained Wexler, adding that, “chorea is not just a mere inconvenience, it can prevent Huntington’s disease patients from walking, talking, working, watching television and almost every aspect of one’s life.”

Wexler called the approval of Xenazine a breakthrough for the Huntington’s disease community, and that everyone was still hopeful that one day there will be a cure.

Click here for FDA Office of Orphan Products Development.

Click here for Huntington’s Disease Information webpage at the National Institute of Neurological Disorders and Stroke.

Click here for Hereditary Disease Foundation

Sources: FDA, Hereditary Disease Foundation.

Written by: Catharine Paddock, PhD