CA-4948 is granted orphan drug designation by FDA for the treatment of AML

CA-4948 is a first-in-class, small molecule inhibitor of interleukin-1 receptor-associated kinase 4 (IRAK4) that plays a role in toll-like receptor (TLR) and interleukin-1 receptor signaling pathways. These pathways are known to be dysregulated in non-Hodgkin lymphoma (NHL), acute myeloid leukemia (AML), and myelodysplastic syndromes (MDS). Very recently, the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to CA-4948 for the treatment of AML.^1,2

In AML patient samples, IRAK4 was identified as the most dominant alternatively-spliced isoform and the long form of IRAK-4 (IRAK-L), which encodes a mutant IRAK4 protein with an additional exon, was found to be associated with maximum pathway activation through interaction with the Myddosome protein complex. Inhibiting IRAK4-L activity with CA-4948 resulted in eradication of leukemic activity in AML samples.³

CA-4948 is currently under evaluation as an orally administered monotherapy in a phase I study (NCT04278768) in adults with AML or high risk MDS. The preliminary results presented during the 62nd American Society of Hematology (ASH) Annual Meeting showed marrow blast reductions and marrow complete responses with no dose-limiting toxicity. More information can be found here.

It is also under investigation in a phase I trial (NCT03328078) as a monotherapy or in combination with ibrutinib in adults with relapsed or refractory NHL.