During routine pharmacovigilance, FDA identified six fatal cases of amyloid related imaging abnormalities with edema (ARIA-E) early in treatment. These fatalities prompted an in-depth analysis of serious and fatal outcomes of ARIA-E occurring prior to the 5th infusion of Leqembi (lecanemab). This analysis included data from FDA Adverse Event Reporting System (FAERS) reports, literature, and information requested from the applicant.
In the in-depth analysis, FDA identified 101 cases of serious ARIA-E in FAERS. Of these case reports, two (2%) occurred between the 2nd and 3rd infusions, 22 (22%) occurred between the 3rd and 4th infusions, 41 (40%) occurred between the 4th and 5th infusions, and 36 (36%) occurred after the 5th infusion.
In total, 24 cases of serious ARIA-E occurred before the 4th infusion. All 24 patients diagnosed with ARIA-E before the 4th infusion showed symptoms, which prompted an earlier unscheduled MRI for clinical assessment. This case review does not capture asymptomatic patients who may have had ARIA before the 3rd infusion but were not identified until a later timepoint during the regularly scheduled MRIs, potentially underestimating the rate of ARIA-E earlier in the course.
FDA also completed a review of the six fatal cases. Of the six fatalities identified in the original review, only one was initially asymptomatic and identified on the first monitoring MRI (i.e., prior to the 5th infusion). The remaining five developed symptoms within 0-8 days of their most recent infusion prompting urgent MRIs. Four of these cases developed symptoms after the 3rd infusion, and the last case developed symptoms after the 4th infusion. The four fatalities that occurred shortly following the 3rd infusion suggest a developing process that was likely already present at the time of the infusion, given the severity of symptoms and relatively rapid onset after the 3rd infusion. Earlier identification of ARIA-E may lead to a delay or discontinuation of Leqembi treatment to potentially mitigate serious and, in some cases, fatal events.
