High-level results from the ALXN1210-TMA-313 phase 3 clinical trial showed that Ultomiris (ravulizumab) did not achieve statistical significance for the primary endpoint of event-free survival through 26 weeks compared to placebo in adults and adolescents (aged 12 years or older) with thrombotic microangiopathy after Haematopoietic Stem Cell Transplant (HSCT)-TMA. The primary endpoint was defined as the time from randomisation until TMA-related clinical worsening or death, whichever occurred first.

In pediatric patients with HSCT-TMA, the ALXN1210-TMA-314 open-label phase 3 trial of Ultomiris demonstrated clinically meaningful overall survival of 87.2 percent at 26 weeks and 73.4 percent at 52 weeks, as previously disclosed. Alexion, AstraZeneca Rare Disease is advancing regulatory filings for Ultomiris in pediatric patients with HSCT-TMA, based on these results and data from ALX-TMA-502, an external control study, which further supports clinically meaningful benefit on overall survival.

Ultomiris showed a trend toward treatment benefit in adults and adolescents with HSCT-TMA at 26 weeks compared to placebo. Discussions with health authorities are ongoing regarding the interpretation of these data, including in the context of real-world evidence.

Following HSCT, a procedure used with increasing frequency to treat some types of cancers and other diseases, the devastating and potentially life-threatening complication of TMA may occur. TMA can result in blood clots and damage to the walls of the smallest blood vessels in the circulatory system, which may lead to organ failure and death. HSCT-TMA is estimated to affect fewer than 6,000 people in the US.

Christopher Dvorak, MD, Professor and Chief of the Division of Pediatric Allergy, Immunology and Bone Marrow Transplantation at UCSF Benioff Children’s Hospitals, said, “Children who develop HSCT-TMA have an extremely poor prognosis without targeted treatment. While the scientific understanding of this condition continues to evolve, survival remains a critical measure of clinical benefit. The overall survival results observed in this phase 3 pediatric trial are clinically meaningful for this young patient population with significant unmet need and may lead to a targeted treatment option for children facing this serious, post-transplant complication.”

The safety profile observed across the ALXN1210-TMA-313 and ALXN1210-TMA-314 trials was consistent with the known safety profile of Ultomiris and with that seen in patients undergoing HSCT.

Vincent Ho, MD, Director of Clinical Operations, Adult Hematopoietic Stem Cell Transplantation and Institute Physician at Dana-Farber Cancer Institute, Professor of Medicine at Harvard Medical School, said, “HSCT-TMA is a serious complication after stem cell transplant with high rates of associated morbidity and mortality and for which effective therapy remains an area of great unmet need. Conducting a global, randomised trial in this complex, life-threatening, post-transplant condition is exceedingly difficult. While the phase 3 trial in adults and adolescents did not meet the primary endpoint, the results add new, important insights to advance the field. Continued evaluation of these data together with results collected from recent, real-world experience will further advance clinical understanding and treatment of this complex transplant complication.”

Alexion plans to present these data at a forthcoming medical meeting.

Marc Dunoyer, Chief Executive Officer (CEO), Alexion, said, “As the largest, global registrational programme conducted across a broad population of patients with HSCT-TMA and the only placebo-controlled trial in this adult population, these trials have demonstrated the potential of Ultomiris to improve survival in pediatric patients with this complex condition. We are moving forward with regulatory filings, with the goal of bringing a new treatment option to pediatric patients with HSCT-TMA and their families as quickly as possible. At the same time, we will continue engagement with global health authorities on potential next steps for the adult indication, as we advance additional analyses in the context of real-world data.”

Ultomiris has been granted Orphan Drug Designation (ODD) in the US and Japan for the treatment of HSCT-TMA, as well as Breakthrough Therapy Designation (BTD) by the US Food and Drug Administration (FDA) for the treatment of paediatric patients with HSCT-TMA.