AstraZeneca has shared data it believes can rescue anselamimab from a phase 3 failure, linking the drug candidate to a 62% improvement in survival among a prespecified subgroup of patients with light chain (AL) amyloidosis.
The placebo-controlled phase 3 trial enrolled 406 patients with the rare disease, which is defined by the accumulation of amyloid fibrils in tissues and organs. Caelum Biosciences, which AZ acquired in 2021, developed the anti-fibril therapy based on evidence it improves organ function by reducing or eliminating amyloid deposits. The idea took a hit in July, when the British drugmaker reported that its phase 3 trial missed its primary endpoint.
Yet AstraZeneca immediately pitched a subgroup as a path forward for anselamimab and embarked on a regulatory strategy that could yield (PDF) approval this year. The Big Pharma used the American Society of Clinical Oncology annual meeting to unveil the data behind the plan.
The strategy centers on a prespecified subgroup of patients with kappa predominant light chain isotype. About 20% of the estimated 74,000 patients living with AL amyloidosis have the kappa light chain form of the disease.
In the 72-patient subgroup, 31.3% of people taking anselamimab died compared to 58.3% of participants on placebo. The annual frequency of cardiovascular hospitalizations was 0.41 on anselamimab and 1.4 on placebo. AstraZeneca called the data nominally statistically significant and highly clinically meaningful.
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The seeming benefits of anselamimab in the subgroup failed to translate into a win for the overall trial because the drug candidate was no better than placebo in a cohort of patients with the more common lambda isotype.
Among the 328 patients with the lambda isotype in the study, the mortality rate was 33.3% on anselamimab and 33.9% on placebo. Similarly, the annual frequency of cardiovascular hospitalizations among these patients was 0.66 on anselamimab and 0.76 on placebo. On placebo, lambda patients were numerically less likely to die or be hospitalized for cardiovascular issues than kappa patients.
Earlier assessments of anselamimab found the antibody bound misfolded light chains, regardless of the kappa or lambda subtype. The broad spectrum gave the molecule a potential edge over birtamimab, a rival AL amyloidosis candidate that Prothena axed last year in response to a phase 3 flop.
