azacitidine + sonidegib

This combination therapy consists of azacitidine, a hypomethylating agent, and sonidegib (LDE255), an oral Smoothened (SMO) antagonist. Azacitidine is a pyrimidine nucleoside analog that inhibits DNA methyltransferases, leading to DNA hypomethylation and the reactivation of tumor suppressor genes. Sonidegib targets the Hedgehog signaling pathway by binding to and inhibiting the SMO receptor, which is often aberrantly activated in myeloid malignancies and contributes to the maintenance of leukemic stem cells. The combination was primarily investigated by the Groupe Francophone des Myelodysplasies (GFM) in a Phase Ib study for patients with high-risk myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), or chronic myelomonocytic leukemia (CMML) who had failed prior azacitidine monotherapy, aiming to overcome resistance by targeting both epigenetic and developmental signaling pathways.

Brand names

VidazaOdomzo

Other names

azacitidine + LDE255