FDA Puts Emavusertib Clinical Trial for R/R AML and MDS on Partial Hold
The FDA has placed a partial hold on Curis’ phase 1/2a clinical trial of emavusertib in adult patients with relapsed/refractory (R/R) acute myelogenous leukemia (AML) or high-risk myelodysplastic syndrome (MDS).
The agency decision is requesting additional data from the company, including efficacy and safety data, but also data related to rhabdomyolysis and information on planned emavusertib dosage in a phase 2 study, given that a participant with R/R/ AML who had rhabdomyolysis died in the trial as a result of an identified dose-limiting toxicity of emavusertib.
Emavusertib is an investigational drug that is a small-molecule interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor that was granted Orphan Drug Designation in 2021.
Upon oral administration, emavusertib targets, binds to, and blocks the kinase activity of IRAK4. This inhibits IRAK4-mediated signaling, prevents the activation of IRAK4-mediated nuclear factor-kappa B (NF-kB) signaling and decreases the expression of inflammatory cytokines and certain pro-survival factors. This inhibits proliferation of IRAK4-overactivated tumor cells, which are found in cells harboring MYD88 activating mutations or those with overactivated toll-like receptor (TLR) pathways.
Patients already enrolled in the trial are allowed to continue taking the drug at 300 mg or lower twice a day, but no new patients can enroll in the study at the moment.
April 5, 2022
