FDA REVIEW OF VIGABATRIN (Sabril®)

I started the year by participating in the FDA Advisory Board review of vigabatrin (VGB)(Sabril®). The FDA expert panel considered whether the drug is effective and safe for treatment of (a) partial onset seizures and (b) infantile spasms, on sequential days. It is important to note that VGB has been in use in countries for more than a decade around the world except for the USA. When first tested for partial onset seizures, it was considered highly valuable at a time when few other drugs were available in the early 1980s. Doctors soon noticed that it also was highly effective in treating babies with infantile spasms, a severe form of epilepsy that often leads to slow development and lifelong seizures.

However, after several years, doctors discovered that some patients had decreases in peripheral (side) vision, called visual field deficits. When this happens, people lose the ability to see around the edges of their eye; their range of vision becomes more central. However, people often do not notice the changes because they accommodate by turning their heads slightly to see what is on the side. That news greatly decreased the number of patients starting VGB, largely restricting its use to people who had not been controlled on several other drugs (considered treatment-resistant).

Over the years, VGB has been reviewed and disapproved three times by FDA for use in the USA. Nonetheless, some people have been able to import the drug from Canada or Europe to continue to use it or to start VGB when other treatments for partial onset seizures for infantile spasms failed. This situation brought a useful treatment to a select few — how unfair! I asked the Advisory Committee to give people the freedom of choice.

The discussion for treatment of partial-onset epilepsy centered on the risk of visual field deficits that occur in more than a quarter of patients who take the drug long-term. Despite years of experience with VGB, we do not know who will be affected or how rapidly it occurs. Testing requires a lot of cooperation by the patient making it impossible for those have limited capacity to understand the instructions and stay still throughout testing. Although visual field deficits also are a concern for babies with infantile spasms, the urgency for rapid treatment may outweigh the risk for limited vision in later life. Babies also are treated for shorter periods than adults with partial-onset seizures. I suggested that adults should be given the opportunity to try vigabatrin for 3 months and babies for 2-3 weeks to determine whether their seizures improve. If not, the drug would be stopped with little risk of visual problems after brief treatment. Give people freedom to choose!

The Advisory Committee discussed who should be eligible for VGB, trying to define "severe" epilepsy. Dr. Weinstein (New York) noted that a history of poor seizure control with 2 or 3 drugs seemed too early, considering the dozen drugs widely available. He felt that VGB should be reserved for use after multiple drugs had been ineffective. Yet, no specific definition could be made. Dr. Mizrahi (Houston) said: "Intractability is a state that can’t be defined, but you know it when you see it."

After extensive discussion of the risks and benefits of treatment, the Advisory Committee voted unanimously to recommend approval of vigabatrin (Sabril) for the treatment of refractory partial-onset seizures and infantile spasms, with a special safety monitoring program. I am delighted that Americans will have access to this useful medication.

This is one of the ways in which Epilepsy Therapy Project supports new treatments for people with epilepsy. We start with grant support to scientists, seed investments to start-up companies, advising investors, matchmaking between entrepreneurs and venture capital groups, and presentations of therapies in development (the "pipeline") to showcase the future. When you make a donation to ETP, these are the activities you support. Thank you!

Wishing you a seizure-free year in 2009,

Joyce Cramer
President, Epilepsy Therapy Project