sonidegib + ruxolitinib

Combination of the Hedgehog pathway inhibitor sonidegib and the Janus kinase inhibitor ruxolitinib, evaluated primarily for myelofibrosis to improve spleen volume reduction and symptom control over JAK inhibition alone. Mechanistically, sonidegib selectively inhibits Smoothened in the Hedgehog signaling pathway, while ruxolitinib inhibits JAK1 and JAK2 to reduce dysregulated cytokine signaling. Clinical development in myelofibrosis reached phase 1b/2; the recommended phase 2 dose identified was sonidegib 400 mg once daily plus ruxolitinib 20 mg twice daily for JAK inhibitor–naive patients. Despite tolerability, further development in myelofibrosis was not pursued due to modest benefit compared with ruxolitinib monotherapy.

Other names

sonidegib and ruxolitinib