FDA Clears Addition of Final Analysis to Phase 3 Study of Uproleselan in AML
A time-based pathway to final analysis has been cleared by the FDA to evaluate the effect of uproleselan on relapsed/refractory acute myeloid leukemia.
The FDA has cleared the addition of a protocol amendment for a phase 3 study (NCT03616470) of uproleselan (GMI-1271) for relapsed/refractory (R/R) acute myeloid leukemia (AML).1
The amendment will allow a time-based analysis of the primary end point of the trial, overall survival (OS), and the final analysis will be conducted if the 295 survival events originally planned for an event driven analysis have not been observed.
As part of the protocol amendment, the FDA also cleared the addition of landmark event-free survival (EFS) and OS analyses as secondary end points. Topline results are now expected by the end Q2 2024.
“We are pleased the FDA cleared the addition of a time-based pathway to final analysis as it provides the opportunity to evaluate the effect of uproleselan on R/R AML based on a clinically mature database with more than 3 years median follow-up,” said Harout Semerjian, chief executive officer of GlycoMimetics, in a press release. “This approach is consistent with regulatory precedent adopted for a prior pivotal AML study for an approved drug and reflects our commitment to science-driven analysis as we seek to deliver uproleselan to R/R AML patients in need of new treatment options as soon as possible.”
Previously, an event based final analysis of OS was expected after the end of 2022. However, the number of events slowed, leading to the extension of the timeline for the study.
Now, the time-based final analysis for 2024 is expected to yield a clinically mature dataset to further assess treatment with uproleselan in R/R AML. The dataset is expected to reflect a median follow-up of more than 3 years, including at least 2 years of post-transplant data.
The randomized, double-blind, phase 3 trial of uproleselan enrolled a total of 388 patients across 70 sites in 9 countries in November 2021. Patients enrolled in the experimental arm of the study were given uproleselan in combination with mitoxantrone, etoposide, and cytarabine, or fludarabine, cytarabine, and idarubicin while those in the placebo comparator arm were given the same combination but with placebo in place of uproleselan.2
Patients were eligible for enrollment if aged ≥18 years and ≤75 years with relapsed or refractory AML who have had no more than 1 prior stem cell transplant, who had not received the chemotherapy regimen to be used for induction on this trial, and those considered medically eligible to receive the chemotherapy regimen to be used for induction on this trial.
The primary end point of the trial is OS, and secondary end points are rate of severe oral mucositis and overall response rates. Other outcomes include EFS, duration of remission, adverse events, and pharmacokinetic exposure.
