The constructive criticism we raise below is relatively minor in the overall assessment of this well done story.
Immunoglobulin infusions have been used to treat a variety of presumed immunologic conditions. So it is not surprising that attempts have been made to treat neurologic conditions such as Guillain-Barre syndrome, multiple sclerosis and Alzheimer’s Disease. There have been four published trials studying the value of immunoglobulin therapy in patients with Alzheimer’s; all for only 6 months evaluation. This new and very small study is the first to demonstrate the potential durability of the treatment over a prolonged period of time. As the story states, experimental drugs gain followings very quickly among Alzheimer’s patients and their families for understandable reasons. The calm, cautious, contextual delivery of this story was appreciated.
The story explained that the cost can be more than $50K/year.
The story didn’t give a clear picture of how many were enrolled in the study and what happened to them.
Reuters did a better job, reporting:
Relkin presented three-year data on 16 patients in Baxter’s Phase 2 study of Gammagard, which originally enrolled 24 participants.
Overall, all 11 study participants who got Gammagard for the full three years showed improvements in thinking abilities, behavior and daily functioning.
Of these, the four patients who received the most effective dose (0.4g/kg) for the full 36 months fared the best, showing no decline on several standard measures of cognition, memory, daily functioning and mood.
But Reuters also didn’t explain what happened to the other 8 participants originally enrolled.
The story didn’t report on what side effects were observed in the study. But we’ll give it the benefit of the doubt for at least citing the experience of one doctor who has used the drug:
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.
We appreciate the fact that “tiny” was the second word in the story – referring to the size of the study. The headline was appropriately cautious.
Independent experts added important analysis:
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.”
For anyone interested, here is the abstract.
Three Year Follow-up on the IVIG for Alzheimer’s Phase II Study
Norman Relkin, Lara Bettger, Diamanto Tsakanikas, Lisa Ravdin
Weill Cornell Medical College, New York, New York, United States
Background: Intravenous Immunoglobulin (IVIG) is under study as an agent for immunotherapy of Alzheimer’s Disease (AD). Positive results of a Phase 2 double-blind placebo-controlled study of IVIG for mild to moderate AD were previously reported. The 24 participants in that study underwent 6 months of placebo controlled treatment followed by a 12 month open-label extension in which all subjects received IVIG. To evaluate the long term effects of IVIG, participants were offered additional IVIG treatment at a standardized dose under an IRB-approved extension protocol.
Methods: Subjects who participated in the Phase 2 study and consented to continuation of treatment were given IVIG (Gammagard, Baxter) 0.4g/kg/2 weeks beginning at post-enrollment month 18. Subjects returned for clinical evaluations at 6 months intervals. A battery of cognitive, functional and behavioral measures were administered at each visit. Adverse events were tracked throughout the study.
Results: IVIG treatment was well tolerated. A total of 16 of the originally enrolled subjects received treatment through month 36. This included 5/8 originally treated with placebo, and 11/16 given IVIG at various doses from time of randomization. Subjects who were treated with IVIG 0.4g/kg/2 weeks for the full 36 months had the best outcome, with no decline in ADAS-Cog, CGIC, 3MS, ADCS-ADL, NPI or QOL measures at the 3 year endpoint. In contrast, subjects treated with placebo initially or IVIG at other doses declined significantly.
Conclusions: This is the first study to report long term stabilization of AD symptoms with IVIG treatment over a period of 36 months. Limitations of the study include the small number of participants and the biases inherent in an open label extension study. The GAP Phase 3 trial is currently in progress and will provide pivotal data on the safety and efficacy of 18 months of IVIG treatment of AD.
No disease mongering in the story.
Excellent use of independent expert perspectives. A true strength of the piece.
The story does note the existence of at least one other drug: “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.” But the story didn’t provide details, nor compare those findings with the new ones.
We wish the story had included a simple line, as the Reuters story did:”There are no licensed drugs that can slow the progression of Alzheimer’s, and currently approved medications only treat symptoms.”
The story was very clear about availability issues and about concerns over off-label use:
“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.”
The story made it clear that this is not a new drug:
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.
We always like to see studies like these placed into context however. It took us less than five minutes to identify 4 earlier published studies using intravenous immunoglobulins as a treatment for Alzheimers. The interest in this study has more to do with the apparent duration of the effect with continued treatment rather than simply the novelty of its use.
The story did not rely on a news release.