Baxter International Inc. : WSJ : Immune-Disorder Drug Shows Promise for Alzheimer's
07/17/2012| 01:11pm US/Eastern
By Shirley S. Wang
A tiny but promising new study suggests that a medicine on the market for immune disorders may offer long-term benefits to Alzheimer's patients, a result likely to spur interest in using the therapy off-label even though it is in limited supply.
The treatment, intravenous immunoglobulin therapy, or IVIG, is an infused therapy made from the blood plasma of healthy young adults. It had shown early promise for Alzheimer's, the memory-robbing ailment that afflicts some five million Americans, since 2004.
The new data showed that four patients with a mild to moderate form of the disease who had been taking an IVIG drug for three years experienced a stabilization of cognitive ability and behavior, meaning their symptoms didn't get worse over that time, according to Norman Relkin, a neurologist at the Weill Cornell Medical College in New York who presented the findings at the Alzheimer's Association International Conference in Vancouver, British Columbia.
The finding is striking because people diagnosed with Alzheimer's typically will see dramatic memory declines within 18 months, if not much earlier, according to experts. Indeed, the 20 patients who had taken the drug, Baxter International Inc.'s (BAX) Gammagard, for fewer than three years or who were taking a different dose declined significantly from the last time they were tested, 18 months ago.
The results suggest Gammagard "is a viable long-term therapy in this group [of Alzheimer's patients]," said Dr. Relkin.
These new data are the longest follow-up to date on patients from Baxter's midstage clinical trial. Earlier results were encouraging enough to prompt the company in 2007 to move Gammagard into late-stage testing for Alzheimer's. The phase III results are expected in early 2013.
William Thies, chief medical and scientific officer of the Alzheimer's Association, called the findings "tantalizing" but said more work is needed. "The data leaves me wanting more," said Dr. Thies, who wasn't involved in the study.
It is important to be cautious about the results because of the small sample size and because patients and investigators knew the patients were getting the medicine, which could have influenced the findings, said Rudy Tanzi, a neurology professor at Harvard Medical School.
"We have to wait for a proper phase III [trial] before we reach a conclusion," said Dr. Tanzi, who wasn't involved with the current study. "It's almost like a crapshoot; it's just too small to predict."
Nevertheless, doctors who work with Alzheimer's patients say they expect patients and families to clamor for the drug. Many say they have been asked about Gammagard for years, and this latest positive result, however small, is likely to bring an increase.
In February, when results in mice were published suggesting that a skin-cancer drug, bexarotene, was beneficial for Alzheimer's, many patients started calling their doctors to find out more about the drug and whether they or a family member should use it off-label.
A spokesman for Baxter said the company "does not support the use of its therapies for unapproved indications. Further, it remains difficult to monitor the use of our IG products for Alzheimer's disease."
Drugs must be approved by the Food and Drug Administration for specific uses, but doctors can prescribe them to patients for other purposes. With any off-label use, there are concerns about safety and efficacy. With Gammagard, there is an additional concern about supply.
IVIG is costly and difficult to make. Baxter says it takes 130 plasma donations to make enough to treat one patient with primary immunodeficiency today. The amount varies based on patient weight and the disease.
"The findings are highly promising but nevertheless a double-edged sword due to the limited supply," said P. Murali Doraiswamy, an Alzheimer's researcher at Duke University who wasn't involved in the study but previously served as an adviser to Baxter. "The growing off-label demand for Alzheimer's could threaten supply for immunodeficient patients."
It isn't clear how the treatment works to treat Alzheimer's, but it appears to take advantage of natural antibodies the body makes that combat a protein called amyloid, which clumps in the brains of people with Alzheimer's.
The drug is approved for uses in a number of conditions, particularly diseases of the immune system, and many patients who use it have life-threatening conditions. There are multiple manufacturers of IVIG, but only Gammagard is in advanced clinical testing for use in treating Alzheimer's disease.
Gayatri Devi, director of the New York Memory Services, has used Gammagard to treat Alzheimer's patients for about seven years. She says she started trying it after a patient's husband approached her about the idea in 2005 after hearing about an early clinical-trial result on TV.
The patient, who had been diagnosed with the disease about eight years before she started Gammagard, had trouble walking and talking, and Dr. Devi was skeptical. The husband insisted, she recalled. That patient experienced impressive improvements in her language and movement, Dr. Devi said.
Dr. Devi has since treated several patients with Gammagard, which involves lengthy office infusions every two to three weeks. She says she measures patients' functioning before starting treatment and six months later to see whether they should continue.
She began with patients whose functioning seemed to be deteriorating significantly and more recently has started treating mild patients to see if she can slow the disease progression. About 70% of her patients have responded, to varying degrees, though none as significantly as that first patient, said Dr. Devi. Only about 5% of her patients are in a position to afford it. Its cost can be more than $50,000 a year, and its use in Alzheimer's isn't covered by insurance.
Several of her patients have exhibited side effects. One developed a serious allergic reaction, two had kidney insufficiencies that reversed when they stopped and a few have had mild skin rashes that went away as they stayed on the treatment.
"The jury is still out [about Gammagard], but there's a lot of evidence that suggests that something like this seems to help a significant proportion of patients with Alzheimer's who currently don't have any other available treatments," said Dr. Devi.
-Write to Shirley S. Wang at email@example.com
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