Ultomiris (ravulizumab) demonstrated clinically meaningful overall survival of 87% at 26 weeks in children with thrombotic microangiopathy after haematopoietic stem cell transplant in Phase III open-label trial

Results support potential to address a life-threatening post-transplant complication with no approved treatment options

Initial results from the ALXN1210-TMA-314 Phase III trial showed that Ultomiris (ravulizumab) demonstrated clinically meaningful overall survival at 26 weeks in paediatric patients (aged 28 days to <18 years of age) with thrombotic microangiopathy (TMA) after haematopoietic stem cell transplantation (HSCT). The data were presented today at the European Hematology Association (EHA) 2025 Congress in Milan, Italy.1

Data from the global, Phase III, open-label, single-arm study showed that overall survival, a secondary endpoint, was 92.6% (38/41; 95% confidence interval [CI]: 78.8-97.6) at day 100 and 87.2% (36/41; 95% CI: 71.8-94.5) at week 26.1

Results showed 17.1% (7/41, 95% CI: 7.2-32.1) of participants achieved the primary endpoint of complete TMA response (a composite measure of haematologic and renal parameters) during the 26-week treatment period. Of the 41 participants, 29 (70.7%, 95% CI: 54.5-83.9) met at least one TMA response criterion and 22 participants (53.7%, 95% CI: 37.4-69.3) met one or two response criteria, with clinically meaningful improvements observed across the components of TMA response. In particular, 58.5% (24/41, 95% CI: 42.1-73.7) and 53.7% (22/41, 95% CI: 37.4-69.3) of participants met the predefined response criteria for platelet and urine protein-to-creatinine ratio (UPCR), respectively, and 36.6% (15/41, 95% CI: 22.1-53.1) of participants normalised lactate dehydrogenase (LDH) from baseline during the 26-week treatment period.1

HSCT-TMA is a rare, severe and potentially life-threatening type of TMA that can occur following HSCT, a procedure to treat some types of cancers and other diseases.2 TMAs are a group of severe and potentially life-threatening rare disorders that cause blood clots and damage to blood vessels, which can cause injury to organs that may lead to organ failure and death.3 The prognosis of HSCT-TMA can be poor if not recognised early, with six-month overall survival rates estimated to be as low as 18% in paediatric patients, with high variability reported in scientific literature dependent on the severity of the condition.4

Franco Locatelli, MD, PhD, Head of the Department of Paediatric Hematology and Oncology, IRCCS Bambino Gesù Children’s Hospital and Professor of Paediatrics, Catholic University of the Sacred Heart in Rome, Italy, as well as an investigator for the ALXN1210-TMA-314 Phase III trial said: “The impact of HSCT-TMA on patient outcomes is devastating, particularly among high-risk populations, such as children, for whom there are currently no targeted therapies approved to treat this rare, severe and potentially life-threatening condition. The response rates and the overall survival observed with ravulizumab may be a practice-changing advancement in this field, providing a potentially effective option for these young patients and their families.”

Gianluca Pirozzi, Senior Vice President, Head of Development, Regulatory and Safety, Alexion, AstraZeneca Rare Disease, said: “These promising results highlight the potential of Ultomiris to transform outcomes for children with HSCT-TMA. Additionally, we continue to evaluate Ultomiris in adults and adolescents suffering from this devastating, rare condition. Together, these two trials represent the largest, global, Phase III programme in patients with HSCT-TMA.”

The primary endpoint of complete TMA response is a composite endpoint that required specific criteria to be met simultaneously across all haematologic and renal parameters at two separate time points at least 24 hours apart and at any measurement taken between those assessments. While the scientific understanding of HSCT-TMA as a post-transplant complication continues to evolve, survival remains a critical measure of clinical benefit in this patient population.

Results from the Phase III trial showed treatment with ravulizumab was well tolerated, and the safety profile was consistent with that observed in previous clinical studies of ravulizumab in other indications.1  

In addition to the paediatric trial, the safety and efficacy of ravulizumab is also being evaluated in a separate, randomised, double-blind, placebo-controlled, Phase III trial (ALXN1210-TMA-313) in adults and adolescents (aged 12 years or older) with HSCT-TMA.5 Together, these studies represent the largest, global, Phase III programme across a broad population of patients with HSCT-TMA (including adult and paediatric patients), underscoring the potential to advance a new treatment option for this rare and severe condition.

Notes

HSCT-TMA
Haematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA) is a rare, severe and potentially life-threatening type of TMA that occurs following HSCT, a procedure to treat some types of cancers and other diseases. It is thought that factors associated with HSCT (i.e., conditioning regimens and other complications) induce overactivation and/or dysregulation of the complement system, driving HSCT-TMA. Symptoms of HSCT-TMA can overlap with those of other conditions, which can lead to a misdiagnosis and/or a significant delay in receiving an accurate diagnosis.2 HSCT-TMA is associated with significant morbidity and six-month overall survival rates estimated to be as low as 18% in paediatric patients and 26% in adults, with high variability reported in scientific literature dependent on the severity of the condition.4

TMAs are a group of severe and potentially life-threatening rare disorders that cause blood clots and damage to the walls of the smallest blood vessels in the circulatory system. These blood clots can cause injury to organs that may lead to organ failure and death.3 Signs, symptoms and complications of TMA include organ damage (most commonly in the kidneys), low platelet count, red blood cell abnormalities [i.e. anaemia, fragmented red cells (schistocytes)], blood clots and high blood pressure.6-9

ALXN1210-TMA-314
ALXN1210-TMA-314 is a global, Phase III, open-label, single-arm, multicentre study evaluating the safety and efficacy of ravulizumab in paediatric patients (aged 28 days to less than 18 years of age) with thrombotic microangiopathy (TMA) after haematopoietic stem cell transplantation (HSCT). Participants were required to have received HSCT within the past 12 months at the time of screening, as well as a diagnosis of TMA that persisted for at least 72 hours after the initial management of any triggering condition or agent.10

The dosing regimen was confirmed based on data analysis after at least 10 participants had completed 21 days of treatment. All patients received a loading dose of ravulizumab on Days 1, 5 and 10, followed by regular weight-based maintenance dosing of ravulizumab beginning on Day 15 and administered every four weeks for patients weighing less than 20 kg or every eight weeks for patients weighing at least 20 kg through the 26-week treatment period, in addition to best supportive care. The administration of supplemental doses of ravulizumab between maintenance doses was guided by prespecified protocol requirements.1

The primary endpoint is complete TMA response (defined as a composite measure of haematologic and renal parameters) at 26 weeks. Secondary endpoints include overall survival, non-relapse mortality and TMA response criteria. Upon completion of the treatment period, patients were followed for an additional 26 weeks. The trial enrolled 41 patients from seven countries across North America, Europe and Asia.10

Ultomiris
Ultomiris (ravulizumab), the longest-acting C5 complement inhibitor, provides immediate, complete and sustained complement inhibition. The medication works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system. When activated in an uncontrolled manner, the complement cascade over-responds, leading the body to attack its own healthy cells. Following a loading dose, Ultomiris is administered intravenously every eight weeks in adults, or every four or eight weeks in paediatric patients (based on body weight).

Ultomiris is approved in the US, EU, Japan and other countries for the treatment of certain adults with paroxysmal nocturnal haemoglobinuria (PNH) and for certain children with PNH in the US and EU.

Ultomiris is also approved in the US, EU, Japan and other countries for the treatment of certain adults and children with atypical haemolytic uraemic syndrome (aHUS).

Additionally, Ultomiris is approved in the US, EU, Japan, China and other countries for the treatment of certain adults with generalised myasthenia gravis (gMG).

Further, Ultomiris is approved in the US, EU, Japan and other countries for the treatment of certain adults with neuromyelitis optica spectrum disorder (NMOSD).

Ultomiris is being assessed as a treatment for additional indications as part of a broad development programme.

Alexion
Alexion, AstraZeneca Rare Disease, is focused on serving patients and families affected by rare diseases and devastating conditions through the discovery, development and delivery of life-changing medicines. A pioneering leader in rare disease for more than three decades, Alexion was the first to translate the complex biology of the complement system into transformative medicines, and today it continues to build a diversified pipeline across disease areas with significant unmet need, using an array of innovative modalities. As part of AstraZeneca, Alexion is continually expanding its global geographic footprint to serve more rare disease patients around the world. It is headquartered in Boston, US.

AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca.

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References

  1. Schoettler M, et al. Ravulizumab plus best supportive care to treat pediatric patients with hematopeietic stem cell transplantation-associated thrombotic microangiopathy: first results from a Phase 3 trial. Presented at European Hematology Association 2025 Congress; 12-15 June 2025; Milan, Italy. Abstract S269.
  2. Meri S, et al. The role of complement in HSCT-TMA: basic science to clinical practice. Adv Ther. 2022;39(9):3896-3915.
  3. Brocklebank V, et al. Thrombotic microangiopathy and the kidney. Clin J Am Soc Nephrol. 2018;13:300-317.
  4. Dandoy C, et al. Survival outcomes in adult and pediatric patients who experienced thrombotic microangiopathy after hematopoietic stem cell transplant: a systematic review and meta-analysis. Blood. 2024;144(1):7286.
  5. ClinicalTrials.gov. Ravulizumab in Thrombotic Microangiopathy After Hematopoietic Stem Cell Transplant. NCT Identifier: NCT04543591. Available here. Accessed June 2025.
  6. Raina R, et al. Atypical hemolytic-uremic syndrome: an update on pathophysiology, diagnosis, and treatment. Ther Apher Dial. 2019;23(1):4-21.
  7. Sallée M, et al. Myocardial infarction is a complication of factor H-associated atypical HUS. Nephrol Dial Transplant. 2010;25(6):2028-2032.
  8. Laurence J, et al. Atypical hemolytic uremic syndrome (aHUS): essential aspects of an accurate diagnosis. Clin Adv Hematol Oncol. 2016;11(11):2-15.
  9. Vorobev A, et al. The phenomenon of thrombotic microangiopathy in cancer patients. Int. J. Mol. Sci. 2024;25(16):9055.
  10. ClinicalTrials.gov. Study of ravulizumab in pediatric participants with HSCT-TMA. NCT Identifier: NCT04557735. Available here. Accessed June 2025.


Veeva ID: GL/H-TMA/0009 V1 06/2025
Date of Preparation: June 2025