ruxolitinib + siremadlin

Ruxolitinib + siremadlin is a **combination therapy under investigation for myelofibrosis (MF)**, particularly in patients with a suboptimal response to ruxolitinib monotherapy. Ruxolitinib is a small molecule inhibitor targeting Janus kinase 1 and Janus kinase 2 (JAK1/JAK2), providing symptomatic relief in MF by modulating JAK-STAT pathways involved in hematopoiesis. Siremadlin (HDM201) is a small molecule inhibitor of human double minute-2 (MDM2), which **restores p53-mediated apoptosis**, potentially inducing clonal regression and reducing spleen volume. The combination aims to address disease drivers in MF, with ruxolitinib acting on JAK-STAT signaling and siremadlin promoting tumor suppressor activity via p53. Early-phase data suggest the drug combination is tolerable, with expected adverse effects (gastrointestinal and hematological toxicities) and signals of clinical benefit, including spleen volume reduction and allele burden drops in JAK2-mutated clones[1][2][6]. Developed and studied by Novartis, this combination has reached phase 1b/2 clinical trials for MF.

Brand names

Jakavi

Other names

ruxolitinibsiremadlin