Pevonedistat in addition to azacitidine is being investigated for the treatment of higher-risk myelodysplastic syndromes (HR-MDS), chronic myelomonocytic leukemia (CMML) and lowblast acute myeloid leukemia (LB-AML). MDS is a group of long-term debilitating and lifethreatening malignant blood disorders in which the bone marrow does not produce enough healthy blood cells. In CMML, the bone marrow produces too many abnormal and immature monocytes which do not work properly. MDS and CMML can lead to severe anaemia, infections or bleeding and result in cancer of the white blood cells (acute myeloid leukemia). There is a high unmet need for transplant-ineligible patients who lack treatment options.
Pevonedistat, administered by IV infusion, blocks the activity of an enzyme in the body called NEDD8-activating enzyme (NAE). NAE is involved in the growth and spread of cancer cells. By blocking NAE in patients with AML, pevonedistat is expected to prevent the degradation of certain proteins affecting key pathways including DNA repair, the cell cycle, and cell survival, thereby preventing the development and worsening of cancer. Chemotherapy drugs, such as azacitidine, work in different ways to stop the growth of cancer cells. If licensed, pevonedistat in addition to azacitidine would offer an additional first-line treatment option for adults with HR-MDS, CMML, or LB-AML.