According to the speaker, why did the overall CARES population fail to meet its primary endpoint, and why is the kappa finding described as a "signal of benefit" rather than a definitive result?
About 75% of enrolled patients had lambda-type amyloidosis, which showed no benefit, while only about a quarter had kappa-type disease; the kappa subgroup analysis was pre-specified but not powered to detect benefit, and the overall primary endpoint was not met.
Most enrolled patients had early-stage cardiac disease, which diluted the treatment effect; the kappa finding came from a post hoc analysis that was not pre-specified.
The trial was stopped early for toxicity in the lambda subgroup, leaving too few kappa patients for a formal efficacy analysis.