AstraZeneca reports Phase III Ultomiris results in HSCT-TMA. Adult trial missed its primary endpoint, while pediatric regulatory filings advance with survival data.
Written By: Anamika Koshti, PharmD
Reviewed By: Pharmacally Editorial Team
On 27 July 2026, AstraZeneca and Alexion, AstraZeneca Rare Disease, announced high-level results from ALXN1210-TMA-313 (NCT04543591), the Phase III trial evaluating Ultomiris (ravulizumab) in adults and adolescents with haematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA). The study did not achieve statistical significance for its primary endpoint of event-free survival through 26 weeks, defined as the time from randomisation to TMA-related clinical worsening or death, compared with placebo.
Alexion confirmed that it is advancing regulatory filings for Ultomiris in paediatric patients with HSCT-TMA, based on previously disclosed results from ALXN1210-TMA-314 (NCT04557735) together with supportive real-world evidence from the ALX-TMA-502 study.
What Is HSCT-TMA?
Haematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA) is a rare, severe, and potentially life-threatening complication that can occur following haematopoietic stem cell transplantation (HSCT). The condition is driven by overactivation and dysregulation of the complement system, leading to blood clot formation, injury to the walls of small blood vessels, organ dysfunction, and potentially organ failure or death.
Because its clinical features overlap with other post-transplant complications, HSCT-TMA may be under-recognized or diagnosed late. One-year survival without targeted treatment has been estimated at 17% to 44% in paediatric patients and 17% to 58% in adults. The condition is estimated to affect fewer than 6,000 people annually in the United States, and no therapy is currently approved specifically for HSCT-TMA.
ALXN1210-TMA-313 Trial Design
ALXN1210-TMA-313 is a global, Phase III, randomised, double-blind, placebo-controlled, multicentre trial evaluating Ultomiris in adults and adolescents aged 12 years or older with HSCT-TMA. The study enrolled 146 patients across 18 countries.
Participants were required to have undergone HSCT within the previous 12 months and to have persistent TMA for at least 72 hours after initial management of any triggering condition or agent.
An initial open-label stage confirmed the Ultomiris dosing regimen after 14 participants completed 21 days of treatment. Patients were subsequently randomised in a 1:1 ratio to receive either Ultomiris plus best supportive care or placebo plus best supportive care for 26 weeks, followed by an additional 26-week follow-up period.
The primary endpoint was event-free survival through 26 weeks, defined as the time from randomisation until TMA-related clinical worsening or death. Key secondary endpoints included overall survival, non-relapse mortality, and TMA response criteria.
Adult and Adolescent Results
ALXN1210-TMA-313 did not achieve statistical significance for its primary endpoint of event-free survival through 26 weeks compared with placebo.
Despite missing the primary endpoint, Ultomiris demonstrated a trend toward treatment benefit in adults and adolescents at 26 weeks. Alexion stated that discussions with health authorities are ongoing regarding interpretation of the findings, including consideration of real-world evidence. Detailed results for the secondary endpoints have not yet been reported.
Paediatric Results: ALXN1210-TMA-314
ALXN1210-TMA-314 is a global, Phase III, open-label, single-arm, multicentre study evaluating Ultomiris in paediatric patients aged 28 days to less than 18 years with HSCT-TMA. The trial enrolled 41 patients across seven countries.
Although the study’s primary endpoint was complete TMA response at 26 weeks, previously disclosed results demonstrated clinically meaningful overall survival of 87.2% at 26 weeks and 73.4% at 52 weeks.
Based on these findings, together with supportive evidence from ALX-TMA-502, an international real-world observational study involving 307 patients across 10 countries, Alexion is advancing regulatory submissions for Ultomiris in paediatric HSCT-TMA. The ALX-TMA-502 study provides historical and real-world overall survival data in complement inhibitor-naïve and eculizumab-treated patients, supporting interpretation of the paediatric trial findings.
The safety profile observed across both ALXN1210-TMA-313 and ALXN1210-TMA-314 was consistent with the established safety profile of Ultomiris and with the expected safety profile in patients undergoing HSCT. No new safety signals were identified in either study.
About Ultomiris
Ultomiris (ravulizumab) is a long-acting C5 complement inhibitor that provides immediate, complete, and sustained inhibition of terminal complement activation. The therapy is approved in multiple countries for several complement-mediated diseases, including paroxysmal nocturnal haemoglobinuria (PNH), atypical haemolytic uraemic syndrome (aHUS), generalized myasthenia gravis (gMG), and neuromyelitis optica spectrum disorder (NMOSD). Ultomiris has received Orphan Drug Designation in the United States and Japan for HSCT-TMA and FDA Breakthrough Therapy Designation for the treatment of paediatric patients with HSCT-TMA.
Clinical Implications
Christopher Dvorak, MD, of UCSF Benioff Children’s Hospitals, said the overall survival observed in the Phase III paediatric trial is clinically meaningful for children with HSCT-TMA, a condition with a poor prognosis and significant unmet medical need.
Vincent Ho, MD, of Dana-Farber Cancer Institute and Harvard Medical School, said that although the adult Phase III trial did not meet its primary endpoint, the findings provide valuable insights that may improve understanding and future management of HSCT-TMA.
Marc Dunoyer, Chief Executive Officer of Alexion, said the company is advancing regulatory filings for paediatric HSCT-TMA while continuing discussions with health authorities regarding the adult programme.
What This Means
The Phase III results present different regulatory outlooks for adult and paediatric patients with HSCT-TMA. In adults and adolescents, failure to achieve the primary endpoint introduces uncertainty regarding the regulatory pathway, although additional analyses incorporating real-world evidence and ongoing discussions with health authorities may inform future development.
In contrast, the paediatric programme continues to advance based on clinically meaningful overall survival data, supportive historical and real-world evidence, and ongoing regulatory submissions. If approved, Ultomiris could become the first targeted therapy available for paediatric patients with HSCT-TMA, a rare condition that currently has no approved treatment.
Alexion plans to present full results from both Phase III studies at an upcoming scientific or medical meeting.
Reference
About the Writer
Anamika Koshti (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, and evidence-based medicine. She has authored peer-reviewed publications on Alzheimer’s disease and PCOS, presented research at national conferences, and gained hands-on experience in medical content development and clinical data interpretation. She is committed to translating complex medical research into accurate, accessible content for healthcare professionals and patients.