AstraZeneca has released findings from two Phase III studies of Ultomiris (ravulizumab) in thrombotic microangiopathy following haematopoietic stem cell transplant (HSCT-TMA) and sonesitatug vedotin (Sone-Ve) in advanced gastric and gastroesophageal junction (GEJ) cancers.<\/p>\n
In the global ALXN1210-TMA-313 Phase III trial, Ultomiris failed to achieve statistical significance for event-free survival through 26 weeks when compared to placebo in adults and adolescents, aged 12 years or above, with HSCT-TMA.<\/p>\n
The primary endpoint measured the time from randomisation to TMA-related clinical worsening or death. A trend toward treatment benefit was observed at 26 weeks, though this did not reach the pre-specified level of statistical significance.<\/p>\n
AstraZeneca said discussions with health authorities regarding the interpretation of data, including the use of real-world evidence, are ongoing.<\/p>\n
In contrast, Ultomiris showed a clinically meaningful overall survival rate in paediatric patients with HSCT-TMA.<\/p>\n
Data from the ALXN1210-TMA-314 open-label Phase III study revealed that overall survival was 87.2% at 26 weeks and 73.4% at 52 weeks.<\/p>\n
Regulatory filings for Ultomiris in this indication are advancing, supported by data from ALX-TMA-502, an external control study.<\/p>\n
The safety profile of Ultomiris across both ALXN1210-TMA-313 and ALXN1210-TMA-314 was observed to be consistent with existing data.<\/p>\n
Ultomiris holds orphan drug designation in Japan and the US for HSCT-TMA, as well as breakthrough therapy designation from the US Food and Drug Administration (FDA) for paediatric patients with HSCT-TMA.<\/p>\n
Separately, AstraZeneca reported that the CLARITY-Gastric01 global Phase III trial showed Sone-Ve, a Claudin 18.2 (CLDN18.2)-targeting antibody drug conjugate, achieved a statistically significant and highly clinically meaningful overall survival improvement.<\/p>\n
This benefit was observed in the second and later-line treatment setting for patients with CLDN18.2-positive advanced gastric, GEJ, or oesophageal adenocarcinoma.<\/p>\n
The improvement was seen when compared to investigator’s choice of therapy.<\/p>\n
The trial met its dual primary endpoint of overall survival in third and later-line settings and a key secondary endpoint in second and later-line patients.<\/p>\n
For the other dual primary endpoint, progression-free survival in the overall population, the trial showed a trend toward improvement without reaching statistical significance. Sone-Ve’s safety profile was consistent with earlier findings, with no new safety signals reported.<\/p>\n
AstraZeneca oncology haematology R&D executive vice-president Susan Galbraith said: “Sone-Ve has the potential to reshape the treatment of gastric cancer by replacing classic chemotherapy with this novel targeted antibody drug conjugate to improve outcomes for patients.”<\/p>\n
Sone-Ve has received orphan drug designation in the US and EU for gastric and GEJ cancers, as well as breakthrough designation in China for the second-line treatment of gastric cancer.<\/p>\n