The FDA has granted clearance to Icobrain Aria, an innovative artificial intelligence (AI) software designed to detect, measure, and grade amyloid-related imaging abnormalities (ARIA), a potential adverse effect linked to new anti-amyloid treatments for Alzheimer's disease (AD). This marks a significant step forward in enhancing the safety and accessibility of AD therapies.
Icobrain Aria, developed by icometrix, is trained using thousands of brain MRI scans to generate a quantitative summary report. This report includes a severity rating score that is seamlessly integrated into the hospital workflow. For ARIA-edema (ARIA-E), the software measures the number of ARIA-E sites, their locations, and the longest axis of the largest site, combining these into an area severity score graded according to clinical guidelines. Similarly, for ARIA-hemorrhages (ARIA-H), the software counts and localizes the number of new microhemorrhages and areas of superficial siderosis, reporting an ARIA-H severity score graded per clinical guidelines.
Clinical Validation and Impact
"Amyloid-lowering treatments represent an important advance in the treatment of Alzheimer's disease but they are associated with a risk of brain swelling and hemorrhage called ARIA," said Stephen Salloway, MD, professor of neurology and psychiatry at the Warren Alpert Medical School of Brown University. "New standardized tools are needed, such as icobrain aria, to assist radiologists and treating clinicians in detecting and managing ARIA to optimize patient safety."
The efficacy of Icobrain Aria was validated in a large-scale study presented at the American Academy of Neurology Annual Meeting. The study involved 16 radiologists evaluating ARIA in 199 cases, both with and without the assistance of Icobrain Aria. The results demonstrated a significant increase in sensitivity and detection for both ARIA-E and ARIA-H when using the AI tool. Specifically, the detection of mild ARIA-E improved from 47.2% to 70.2%, and mild-or-severe ARIA-E detection increased from 83.7% to 95.3%. Similarly, mild ARIA-H detection improved from 60.0% to 71.0%, and moderate-or-severe ARIA-H detection increased from 85.5% to 94.4%. In ARIA-free cases, the specificity of assisted reads was high, ranging from 83.0% to 99.4% depending on the severity and type of ARIA.
Addressing ARIA Concerns in Alzheimer's Treatment
The emergence of ARIA as a potential side effect has been a significant concern with the development and approval of anti-amyloid treatments. Aducanumab (Aduhelm; Biogen), one of the earlier anti-amyloid treatments, showed notable ARIA-E rates in its phase 3 trials, EMERGE and ENGAGE, with rates ranging from 25.5% to 35.5% depending on the dosage. While initially approved, aducanumab faced challenges related to high costs and limited use, leading Biogen to eventually withdraw it from the market.
Lecanemab (Leeqembi; Eisai), another anti-amyloid treatment, demonstrated lower ARIA-E rates (12.5%) in its confirmatory phase 3 study (Clarity AD; NCT03887455). However, ARIA-H still occurred at a rate of 17.3% in lecanemab-treated individuals compared to 9.0% in those on placebo. Prescribing information for lecanemab, which is approved for the earliest stage of AD, recommends testing for apolipoprotein E4 status before initiating treatment to assess ARIA risk.
Donanemab (Kisulna; Eli Lilly), the most recently approved anti-amyloid treatment, was approved based on data from the TRAILBLAZER-ALZ-2 trial (NCT04437511), a large-scale, phase 3, double-blind, placebo-controlled trial involving 1736 patients with early-stage AD. The study reported that 24% of patients experienced ARIA-E, with most events being mild to moderate radiographically. The majority of ARIA-E events occurred after up to three donanemab infusions, and 98% of first ARIA-E events resolved radiographically, with a mean resolution time of approximately 10 weeks. Recurrent ARIA-E was observed in 6% of patients on active treatment.
Implications for Alzheimer's Care
The introduction of Icobrain Aria is expected to streamline care pathways, ensuring timely diagnosis and safe drug prescriptions. George Vradenburg, chairman of UsAgainstAlzheimer’s, emphasized the importance of standardized tools in making Alzheimer's therapies more accessible and safer for patients. The FDA clearance of Icobrain Aria provides clinicians with the necessary tools to make informed and effective treatment decisions, ultimately benefiting families facing Alzheimer's disease.
