Anselamimab in AL amyloidosis: Phase 3 data

By Laura Boyd

Anselamimab did not significantly improve the primary composite endpoint of all-cause mortality (ACM) and cardiovascular hospitalizations (CVH) compared with placebo in patients with advanced cardiac light chain (AL) amyloidosis, according to results from the phase 3 CARES studies (NCT04512235; NCT04504825) presented at the 31st Annual Meeting of the European Hematology Association (EHA2026 Congress).

In the overall population, outcomes were similar between treatment arms. The win ratio for the primary endpoint was 1.1 (P=0.332), and ACM did not differ significantly, with a hazard ratio (HR) of 0.8. Rates of cardiovascular hospitalization were also comparable between groups.

In a prespecified subgroup analysis, outcomes differed by light chain subtype:

• In patients with kappa light chain isotype (κ), anselamimab reduced ACM by 62% (HR, 0.38; P=0.012) and reduced CVH risk by 71% (incidence risk ratio, 0.29; P=0.028)
• No reduction in ACM or CVH was observed in patients with lambda light chain (λ) disease

Kaplan–Meier analyses showed separation of survival curves in the κ subgroup, while curves remained largely superimposed in the overall population and λ subgroup.

Functional outcomes reflected these findings. In the overall population, patient-reported and functional measures did not differ between arms. However, in the κ subgroup, Kansas City Cardiomyopathy Questionnaire scores increased by approximately 10 points (Hodges–Lehmann mean difference) compared with placebo at week 50, exceeding the threshold considered clinically meaningful. Improvements were also reported in 6-minute walk distance.

The CARES program comprised two multicenter, double-blind, randomized, placebo-controlled trials in patients with newly diagnosed, treatment-naive Mayo stage 3a or 3b cardiac AL amyloidosis. Patients received standard anti–plasma cell dyscrasia therapy, including CyBorD (cyclophosphamide, bortezomib, dexamethasone), with daratumumab permitted, and were randomized 2:1 to anselamimab or placebo. In total, 271 patients received anselamimab and 135 received placebo, with median treatment durations of approximately 21.4 and 21.1 months, respectively.

Ashutosh Wechalekar (University College London Hospitals and National Amyloidosis Centre, UK) presented the data and noted that the findings suggest that the intensity and duration of antibody binding may be important, given the differences observed between κ and λ subtypes.

Safety findings were comparable between treatment groups and consistent with advanced cardiac amyloidosis. Grade ≥3 adverse events were common, with similar incidence across arms.

Wechalekar concluded that “anselamimab offers a new therapeutic option directed at clearing the amyloid deposits in patients with newly diagnosed κ light chain AL amyloidosis,” with potential broader applicability beyond cardiac disease, including earlier-stage and other organ involvement, although further data are needed to establish this.

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