Photo by Esther Dyson
Preparing drug for a trial
The US Food and Drug Administration (FDA) has placed a full clinical hold on a phase 1/2 trial of SEL24, a dual PIM/FLT3 kinase inhibitor, in patients with relapsed/refractory acute myeloid leukemia (AML).
The hold is due to a fatal cerebral adverse event that is considered possibly related to SEL24.
The clinical hold means no new patients will be enrolled in the trial and enrolled patients will not receive SEL24 until the hold is lifted.
Selvita S.A., the company developing SEL24, received a clinical hold letter from the FDA on October 6 and said it plans to work with the agency to have the hold lifted.
As part of this process, Selvita will provide the FDA with additional data and analysis on patients treated with SEL24 as well as a proposed protocol amendment.
The trial began in the first quarter of 2017. The study is designed to determine the maximum tolerated dose and recommended dose of SEL24 in patients with relapsed and refractory AML. The study began with a 25 mg daily dose, which was then escalated following cohort reviews.
One AML patient started treatment with a 150 mg dose of SEL24 as the third patient in this dose cohort and received 4 doses of the drug. This patient developed a life-threatening, grade 4 venous thrombus in the brain with subsequent intracerebral hemorrhage, which required hospitalization.
The patient died in hospice 4 days later due to the cerebral event. The patient’s death was subsequently evaluated as possibly related to SEL24.
A safety report and a review of data by the trial’s data monitoring committee were submitted to the FDA. The agency then placed a clinical hold on the trial and requested more safety data on patients who have received SEL24, as well as specific protocol changes and additional guidance to the study staff.
Selvita said it plans to comply with the requests and provide additional information to the agency and clinical trial centers, in collaboration with the Menarini Group, its global development partner for SEL24.
The FDA has 30 days from the receipt of Selvita’s response to let the company know whether the clinical hold is lifted.
