AstraZeneca (AZ) has announced promising results from a late-stage study of its C5 complement inhibitor Ultomiris (ravulizumab) in paediatric patients with a life-threatening post-transplant complication.
The phase 3 ALXN1210-TMA-314 trial has been evaluating the drug in patients aged 28 days to less than 18 years with thrombotic microangiopathy (TMA) after haematopoietic stem cell transplantation (HSCT).
TMAs are a group of rare, severe disorders that cause blood clots and damage to blood vessels, potentially resulting in organ injury. There are currently no approved treatment options for HSCT-TMA, which can occur following HSCT, a procedure to treat some types of cancers and other diseases.
Initial results from ALXN1210-TMA-314, presented at this year’s European Hematology Association congress, showed that overall survival, a secondary endpoint, was 92.6% at day 100 and 87.2% at week 26.
The primary endpoint of complete TMA response was achieved by 17.1% of patients during the 26-week treatment period, while 70.7% met at least one TMA response criterion and 53.7% reached one or two response criteria, with clinically meaningful improvements seen across the components of TMA response.
ALXN1210-TMA-314 trial investigator, Franco Locatelli, 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 [Ultomiris] may be a practice-changing advancement in this field, providing a potentially effective option for these young patients and their families.”
Administered intravenously, AZ’s Ultomiris already holds approvals to treat certain cases of paroxysmal nocturnal haemoglobinuria, atypical haemolytic uraemic syndrome, generalised myasthenia gravis and neuromyelitis optica spectrum disorder.
Alongside the paediatric study, the drug is also being evaluated in the phase 3 ALXN1210-TMA-313 trial of adults and adolescents aged 12 years or older with HSCT-TMA.
Gianluca Pirozzi, senior vice president, head of development, regulatory and safety at Alexion, AstraZeneca Rare Disease, said: “… we continue to evaluate Ultomiris in adults and adolescents suffering from this devastating, rare condition.
“Together, these two trials represent the largest, global, phase 3 programme in patients with HSCT-TMA.”
