The Food and Drug Administration on Friday approved the first drug for treating infantile spasms, a rare and devastating disease that wracks infants with hundreds of spasms every day, interferes with neurological development and kills as many as 20% of victims.
The approval of the drug, called Sabril, represents the end of a 15-year odyssey for Dr. W. Donald Shields, a pediatric neurologist at UCLA's Geffen School of Medicine, who pioneered studies of the drug in the U.S.
The drug, known generically as vigabatrin, is not perfect. As many as 30% of those who use it suffer from a loss of peripheral vision, although it does not affect central vision and such tasks as reading. Patients who use the drug will have to be monitored very closely for loss of vision, but most parents Shields has encountered are not overly concerned about the problem. "If you lose peripheral vision but are developmentally normal, it is probably worth it," he said.
The FDA also approved the drug for use in epilepsy patients suffering a phenomenon called complex partial seizures, which can cause impaired consciousness. About a third of the 3 million American epileptics suffer from such seizures and about a third of those do not get relief with existing drugs. Sabril would be a treatment of last resort for them.
Infantile seizures, which affect about 2,500 American infants each year, usually strikes those ages 3 to 6 months. Victims have as many as 100 seizures per episode, and several episodes a day. Click here to see the frightening episodes. There is no approved treatment for the seizures in the United States, but parents who can afford it have been importing Sabril from Canada and Europe, where it is available.
Vigabatrin was developed by French scientists in the 1970s as a suicide inhibitor of the enzyme gamma-aminobutyric acid transaminase, which breaks down gamma-amino-butyric acid or GABA in the brain. Researchers postulated that infantile seizures were caused by a deficit of GABA in the brain and hoped the drug would raise levels by preventing its destruction. The drug was originally owned by Sanofi-Aventis.
In the early 1990s, Shields talked to the president of Aventis and persuaded him to give his team 65,000 tablets of the drug and to provide funding for a research study. But when the visual-field problem emerged in 1993, the company lost interest in the drug. All of the pills given to Shields expired in 2001, and he had to stop his research. "We thought that was the end of it, even though it works really well for a lot of patients," he said.
At the beginning of this decade, however, he talked to Mike Burke, head of sales and marketing for Ovation Pharmaceuticals Inc. -- now Lundbeck Inc. of Deerfield, Ill. When Burke asked if there were any drugs he needed, Shields pointed him to Sabril. By 2003, Lundbeck had acquired U.S. rights to the drug, and the company helped Shields assemble his data from the previous trial into a form that could be submitted to the FDA. The data were presented to an FDA advisory committee in January, and the committee unanimously recommended approval.
As a condition of approval, physicians who prescribe the drug must do a baseline test of visual acuity before the patient begins taking the drug, and then every three months afterward. It is usually clear within a month or two if the drug is going to work, Shields said. If it doesn't, the patient should stop taking it to avoid side effects that are not counterbalanced by benefits.
In infants, the drug is normally given for six to nine months, then tapered off to see if the symptoms reappear. If they do, then the cycle is repeated.
Because so few infants have the condition, Sabril is designated as an orphan drug, so that the government provides Lundbeck with financial incentives to promote its development.
Some research suggests that the drug is also useful in blocking cravings for heroin and other addictive substances, and Lundbeck has applied for approval for that application as well.
-- Thomas H. Maugh II
Photo: Dr. W. Donald Shields