Amyloid-related imaging abnormalities (ARIA) found in approximately 40% of patients taking “Alzheimer’s drug” Aduhelm

Study: Biogen’s Aduhelm Caused Brain Swelling in Over One-Third of Study Par­tic­i­pants (Bio­Space):

Atten­tion is being focused on a side effect of Biogen’s Alzheimer’s drug, Aduhelm (adu­canum­ab). Even before its con­tro­ver­sial approval on June 7, there were cas­es of amy­loid-relat­ed imag­ing abnor­mal­i­ties (ARIA‑E), or cere­bral ede­ma, observed in the trials.

On Novem­ber 10, the com­pa­ny indi­cat­ed it was inves­ti­gat­ing the death of a 75-year-old woman who died of ARIA while receiv­ing Aduhelm. It has yet to be deter­mined if the death was caused by the ARIA. Between July and Sep­tem­ber, three oth­er cas­es of ARIA were sub­mit­ted to the U.S. Food and Drug Administration’s adverse event data­base. All of those ARIA cas­es required hos­pi­tal­iza­tion and are being reviewed by Biogen.

One con­cern expressed by some physi­cians is that the peo­ple in the orig­i­nal clin­i­cal tri­als were gen­er­al­ly healthy except for their ear­ly Alzheimer’s dis­ease. Peo­ple with oth­er comor­bidi­ties were often exclud­ed from the tri­als to elim­i­nate con­fus­ing clin­i­cal sig­nals. But now that the drug is approved, peo­ple with oth­er health prob­lems would be eli­gi­ble for the drug, which might lead to more adverse side effects … The researchers found 425 cas­es in the com­bined adu­canum­ab group expe­ri­enced ARIA (41.3%), and ARIA-ede­ma was iden­ti­fied in 362 patients or 35.2%. Of them, 94 (26%) had symp­toms, such as headache, con­fu­sion, dizzi­ness and nau­sea. They found ARIA-micro­he­m­or­rhage and ARIA-super­fi­cial sidero­sis in 197 patients (19.1%) and 151 patients (14.7%), respectively.

The Study:

Amy­loid-Relat­ed Imag­ing Abnor­mal­i­ties in 2 Phase 3 Stud­ies Eval­u­at­ing Adu­canum­ab in Patients With Ear­ly Alzheimer Dis­ease (JAMA Neu­rol­o­gy). Key Points:

• Ques­tion: What are the char­ac­ter­is­tics of amy­loid-relat­ed imag­ing abnor­mal­i­ties (ARIA) dur­ing adu­canum­ab treat­ment in indi­vid­u­als with ear­ly Alzheimer disease?
• Find­ings: In an inte­grat­ed safe­ty data set of 2 phase 3 clin­i­cal tri­als (EMERGE and ENGAGE) includ­ing 3285 par­tic­i­pants, 425 patients (41.3%) in the com­bined 10 mg/kg adu­canum­ab group (n?=?1029) expe­ri­enced ARIA; ARIA-ede­ma occurred in 362 patients (35.2%), and 94 of these patients (26.0%) expe­ri­enced asso­ci­at­ed symp­toms (eg, headache, con­fu­sion, dizzi­ness, and nau­sea). ARIA-micro­he­m­or­rhage and ARIA–superficial sidero­sis occurred in 197 patients (19.1%) and 151 patients (14.7%), respectively.
• Mean­ing: Amy­loid-relat­ed imag­ing abnor­mal­i­ties occurred in approx­i­mate­ly 40% of par­tic­i­pants in the phase 3 stud­ies of adu­canum­ab, and approx­i­mate­ly one-quar­ter of these patients expe­ri­enced symptoms.

News in Context:

• Vet­er­ans Affairs won’t cov­er Biogen’s new “Alzheimer’s drug” giv­en con­cerns over safe­ty and lack of evidence
• Grow­ing back­lash against the FDA approval of unproven Alzheimer’s treat­ment Aduhelm, by Biogen
• First, do no harm? Six rea­sons to approach anti-amy­loid drug Aduhelm cau­tious­ly, if at all