AstraZeneca (LSE:AZN) said its Ultomiris drug did not achieve statistical significance for the primary endpoint of event-free survival through 26 weeks in adults and adolescents with thrombotic microangiopathy following haematopoietic stem cell transplant (HSCT-TMA), a rare and potentially fatal complication of stem cell transplants.
The ALXN1210-TMA-313 trial compared ravulizumab, marketed as Ultomiris, against placebo in 146 patients across 18 countries, measuring time to clinical worsening or death.
A separate paediatric trial, ALXN1210-TMA-314, fared better, showing overall survival of 87.2% at 26 weeks and 73.4% at 52 weeks in an open-label study of 41 children.
Alexion, AstraZeneca's rare disease unit, is advancing regulatory filings for the paediatric indication based on those results alongside an external control study.
The adult trial showed a trend toward treatment benefit at 26 weeks, and AstraZeneca said discussions with health authorities are ongoing regarding how to interpret that data alongside real-world evidence.
"While the Phase III trial in adults and adolescents did not meet the primary endpoint, the results add new, important insights to advance the field," said Vincent Ho, director of clinical operations for adult haematopoietic stem cell transplantation at Dana-Farber Cancer Institute.
Alexion chief executive Marc Dunoyer said the company is moving forward with paediatric filings while continuing to engage regulators on next steps for the adult indication.
HSCT-TMA is estimated to affect fewer than 6,000 people in the US, with paediatric one-year survival rates historically as low as 17% without targeted treatment.
Alexion plans to present the full trial data at a forthcoming medical meeting.
News Intelligence what this means for the company
Ultomiris failed its Phase III primary endpoint for adult and adolescent post-transplant thrombotic microangiopathy, missing statistical significance on event-free survival at 26 weeks despite a numerical trend toward benefit. The paediatric trial succeeded, allowing Alexion to advance regulatory filings for that narrower indication, but the adult failure—affecting a larger patient population in a rare, life-threatening condition—removes a potential revenue driver and leaves the adult path dependent on post-hoc reinterpretation of trend data and real-world evidence, a weaker regulatory footing.
This is the second Phase III failure in AstraZeneca's pipeline in under a month—following the Ionis ATTR-CM trial miss on 9 July—signalling execution risk in late-stage development. The Ultomiris adult setback narrows the drug's addressable market to paediatric HSCT-TMA (41 patients in the trial) and leaves the company negotiating with regulators on salvage pathways rather than securing a clear approval.
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