After almost a 3-year FDA regulatory process, Xenazine® (tetrabenazine) is finally here. The FDA approved this first drug for Huntington's because of broad agreement from the experts that it gives meaningful benefit to many whose lives are impaired by chorea. And in a careful move required by the FDA, Xenazine® will be available only through a complicated prescribing process that is unique to this drug, which is intended to improve physician education and patient oversight that will address associated risks.
Xenazine® will be made available through Ovation Pharmaceuticals. This review is based on information provided by David Knocke from Ovation, and Dr. Russell Katz from the FDA during the November, 2008 Huntington Study Group Meetings.
Tetrabenazine History: Following the course of this drug shows how difficult it is win FDA approval.
- 2006 February: The pivotal clinical trial, sponsored by Prestwick Pharmaceuticals and administered by Huntington Study Group is published.
- 2006 March: After initial review of Xenazine® data in March 2006, the FDA granted a Letter of Approval. This meant that Prestwick was required to address specific FDA concerns about the drug that included safety, and questions about why chorea benefit in the HSG clinical trial did not translate into improvement in levels of function as measured by the UHDRS, the standard research scale.
- 2007 December: After reviewing additional Prestwick studies in December 2007, members of the Peripheral and Central Nervous System Drug Advisory Committee for the FDA unanimously vote to recommend drug approval. This approval recommendation was based on its ability to lessen the effects of chorea.
- 2008 August: The FDA grants drug approval of Xenazine® for the treatment of chorea in Huntington’s. However prior to making it available to patients, labeling specifics and a special program for prescribing and physician education were required to address safety concerns.
- 2008 September: Prestwick Pharmaceuticals sells the U.S. rights to commercialize Xenazine® to Ovation Pharmaceuticals.
- 2008 November: During the Huntington Study Group Symposium, Ovation announces drug availability (for the week of November 24) and specialized program for delivery to patients.
The Program: The process for getting this drug is harder than most, but for many who suffer from chorea, it will be worth the effort.
- Xenazine® will be available only through specialty pharmacies
designated by Ovation, not local pharmacies beginning the week of
November 24, 2008.
- Your doctor must first obtain specific prescribing forms and information pamphlets from an Ovation source. Ovation representatives will be dispatched to neurology groups and will provide these forms. If your local general doctor provides your Huntington’s care, information and forms must be obtained from Ovation before you can obtain the drug.
- After the doctor faxes the prescription, Ovation will determine whether or how much your insurance will cover the cost. On average, it will take about 3 weeks to receive the drug by mail. Subsequent refills will be more prompt. If financial assistance is requested, the initial process will take longer, but Ovation is willing to supply up to two months of free drug during this process. You will be asked (but not required) to sign a consent form that will enable the company to do follow-up assessments (about your response to the medication and education by your doctor) by phone. This was a requirement for FDA approval.
- Xenazine®, like any new drug for an orphan disease is very expensive. However, Ovation is taking exhaustive steps to provide a financial program to ease the out-of-pocket financial burdens to patients. With appropriate income documentation, Ovation will provide drug -- free of charge -- for those without insurance, and when legal will provide at least partial payment of high co-pays.
- Those requiring doses larger than 50 mg per day will require specialized blood testing. Though this drug comes with a very high price tag, this is customary for new drugs for orphan diseases. In addition the mandated prescribing process and follow-up procedures are labor intensive and expensive to administer. The Huntington’s community owes Ovation a debt of gratitude for serving our orphan disease.
Don’t Leave it only to the Doctor: Educate Yourself! Proper dosage of this drug is very important, and remember to report any side effects to your doctor. The pills come in 12.5 and 25 mg sizes.
- It is advised to start low (12.5 mg/day) and go slow, increasing dosage in one or two week intervals. It is important to see your doctor frequently to establish best dosing -- one that controls some of the chorea -- without causing side effects.
- The goal is to decrease the severity, and not to stop the chorea because the dosages required could lead to serious side effects. Common side effects are fatigue and sleepiness, restlessness, slowness of movement. Depression if not treated is the most serious side effect and has been associated with suicide. Often decreasing the dosage of Xenazine® will control side effects.
- It may be best to use antidepressants other than Prozac® (fluoxetine) and Paxil® (paroxetine), amytriptyline (Elavil®) and nortriptyline (Pamalor®) because of potential drug interference with Xenazine®. If you are already on these medications, smaller dosages should be used, at least initially. Remember too that side effects of other medications (antidepressants, antipsychotics) may be increased by use of Xenazine®.
- In some cases, dosage can be decreased over time while maintaining effect. Though Ovation states the drug may be stopped abruptly for a medical indication, tapering the dose may be more comfortable allowing a more gradual return of chorea.
- Most importantly: Don't forget to see your doctor regularly.