SOHO 2026 | Phase III CARES subgroup analysis: signal of benefit with anselamimab in kappa AL amyloidosis

So the CARES trial was designed as a, there were two separate trials. They were designed for patients with advanced cardiac amyloidosis based on the European modification of the Mayo staging system. There were two trials in patients with stage 3a disease and the very advanced stage 3b disease. The results that have been presented is the combined analysis of both the stage 3a and the stage 3b trials. The primary endpoint is all-cause mortality and cardiovascular hospitalizations analyzed together as a combined endpoint. When this trial was analyzed, the composite endpoint of cardiovascular hospitalizations and all-cause mortality for the whole population, the primary endpoint of this trial was not met. However, when a subgroup analysis of this trial was undertaken for patients with light-chain amyloidosis of lambda type and light-chain amyloidosis of kappa type, and these subgroup analyses were pre-specified, there was no signal of benefit in patients with amyloidosis of lambda type, but there was a signal of benefit in amyloidosis of the kappa type. So patients who had kappa light-chain amyloidosis, there was a clear improvement in the overall survival as well as reduction in cardiovascular hospitalizations in patients treated on the anselamimab arm compared to the placebo arm. But in lambda light chain amyloidosis, there was no benefit of treatment with anselamimab. Now, when we look at the trial as a whole, 75% of patients have got amyloidosis of lambda type, about a quarter of the patients have amyloidosis of kappa type. And therefore, it’s not very surprising that as a whole, the trial results appear to be negative because it seemed to benefit a particular subtype of amyloidosis. Now, on a clinical ground, it’s quite easy to identify which patients have kappa or lambda amyloid because they have the corresponding abnormal light chain in their serum. And then when we type their amyloid protein deposits by proteomics or mass spectrometry, we can identify the amyloid to be of kappa type. So patients who could potentially benefit from this drug could be picked up at the outset based on their light chain isotype and the amyloid fibril type. However, in this trial, this was not the primary endpoint of the overall trial. So this was a subgroup analysis, although it was pre-specified. It is in a subgroup of a patient trial, and the trial was clearly not powered to detect the benefit just for the kappa patients. Therefore we suggest that there is a signal of benefit rather than saying that this is a benefit beyond doubt as the overall endpoint of this trial was not met as the trial was designed but the signal in the kappa patients appears to be fairly strong.

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