They Got a Name, and an Acronym, for That
Amyloid-related imaging abnormalities of edema/effusion, or ARIA-E.
[Insert snarky X-Files/Roswell quip here.]
It's what Alzheimer experts are now calling the brain edema associated with the administration of Pfizer/JNJ's bapineuzumab, and other investigational anti-amyloid compounds, according to an article in last week's Neurology Today. The write-up also highlighted that ARIA-E occurs more frequently than previously thought—in about 17% of bapineuzumab-treated patients (36/210). But about three quarters of these re-examined cases, detected via MRI, were asymptomatic. Risks for the potentially adverse phenomenon were APOE4 homozygosity, a known risk for Alzheimer disease, and a higher dosage of bapineuzumab (more amyloid, more drug).
The Neurology Today report also described the results of a bapineuzumab extension trial, in which the rate (or risk) of ARIA-E declined after the third dose of medication. The lead investigator, Stephen Salloway, presented an unusually cheery picture of the drug's safety (and, by association, brain edema): "The majority of cases of ARIA are asymptomatic and almost all resolve by holding the dose," he was quoted as saying, along with, "Overall, bapineuzumab was generally well tolerated and adverse effects tended to be mild to moderate. Importantly, there were no new safety signals with exposure over five years of treatment." But there were questions among interviewed experts about the high drop-out rate of patients in bapineuzumab trials—a fact suggesting that the drug is not easily tolerated (or is ineffective, or both).*
Image from alzforum.org (reproduced in Neurology Today) showing development and remission of brain edema, aka ARIA-E, on MR images in bapineuzumab-treated patients. Credit given to Stephen Salloway and Reisa Sperling.
The question of bapineuzumab's safety is irrelevant if the drug doesn't improve cognition—which it doesn't seem to, at least not across the board in established Alzheimer disease. Salloway suggested, in an end-quote, that bapineuzumab might have a niche in earlier stages of dementia. But the general subtext of the article (or that of any transmission attempting to mitigate safety concerns about a marginally beneficial compound) is THIS DRUG IS A DEAD DUCK. And the scary generalization from this all-caps inference (and see the N.B. for support) is that all anti-amyloid compounds for Alzheimer disease are in serious jeopardy.
* The results of both of these described studies were presented in July at the Alzheimer’s Association International Conference in Paris.
N.B.—The cause of ARIA-E is unknown but has been entertained frequently at this blog and elsewhere. In the NT article, Dr. Reisa Sperling, suggested that the phenomenon is caused by "transient increases in vascular permeability—leaky vessels—due to mobilization of amyloid from plaque and into vessels and clearance of vascular amyloid." She added further, "I do think the leaky vessel problem will affect the whole class [of amyloid-modifying drugs], but it's manageable." That's one helluva qualified endorsement.
[Insert snarky X-Files/Roswell quip here.]
It's what Alzheimer experts are now calling the brain edema associated with the administration of Pfizer/JNJ's bapineuzumab, and other investigational anti-amyloid compounds, according to an article in last week's Neurology Today. The write-up also highlighted that ARIA-E occurs more frequently than previously thought—in about 17% of bapineuzumab-treated patients (36/210). But about three quarters of these re-examined cases, detected via MRI, were asymptomatic. Risks for the potentially adverse phenomenon were APOE4 homozygosity, a known risk for Alzheimer disease, and a higher dosage of bapineuzumab (more amyloid, more drug).
The Neurology Today report also described the results of a bapineuzumab extension trial, in which the rate (or risk) of ARIA-E declined after the third dose of medication. The lead investigator, Stephen Salloway, presented an unusually cheery picture of the drug's safety (and, by association, brain edema): "The majority of cases of ARIA are asymptomatic and almost all resolve by holding the dose," he was quoted as saying, along with, "Overall, bapineuzumab was generally well tolerated and adverse effects tended to be mild to moderate. Importantly, there were no new safety signals with exposure over five years of treatment." But there were questions among interviewed experts about the high drop-out rate of patients in bapineuzumab trials—a fact suggesting that the drug is not easily tolerated (or is ineffective, or both).*
Image from alzforum.org (reproduced in Neurology Today) showing development and remission of brain edema, aka ARIA-E, on MR images in bapineuzumab-treated patients. Credit given to Stephen Salloway and Reisa Sperling.
The question of bapineuzumab's safety is irrelevant if the drug doesn't improve cognition—which it doesn't seem to, at least not across the board in established Alzheimer disease. Salloway suggested, in an end-quote, that bapineuzumab might have a niche in earlier stages of dementia. But the general subtext of the article (or that of any transmission attempting to mitigate safety concerns about a marginally beneficial compound) is THIS DRUG IS A DEAD DUCK. And the scary generalization from this all-caps inference (and see the N.B. for support) is that all anti-amyloid compounds for Alzheimer disease are in serious jeopardy.
* The results of both of these described studies were presented in July at the Alzheimer’s Association International Conference in Paris.
N.B.—The cause of ARIA-E is unknown but has been entertained frequently at this blog and elsewhere. In the NT article, Dr. Reisa Sperling, suggested that the phenomenon is caused by "transient increases in vascular permeability—leaky vessels—due to mobilization of amyloid from plaque and into vessels and clearance of vascular amyloid." She added further, "I do think the leaky vessel problem will affect the whole class [of amyloid-modifying drugs], but it's manageable." That's one helluva qualified endorsement.
