General Information

Ojjaara (momelotinib) is a kinase inhibitor.

Ojjaara is specifically indicated for the treatment of intermediate or high-risk myelofibrosis (MF), including primary MF or secondary MF [postpolycythemia vera (PV) and post-essential thrombocythemia (ET)], in adults with anemia.

Ojjaara is supplied as tablets for oral administration. The recommended dose is 200 mg orally once daily. Ojjaara may be taken with or without food. Swallow tablets whole. Do not cut, crush, or chew tablets. If a dose of is missed, the next scheduled dose should be taken the following day.

Mechanism of Action

Ojjaara (momelotinib) is an inhibitor of wild type Janus Kinase 1 and 2 (JAK1/JAK2) and mutant JAK2V617F, which contribute to signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function. Momelotinib and its major human circulating metabolite, M21, have higher inhibitory activity for JAK2 compared to JAK3 and tyrosine kinase 2 (TYK2). Momelotinib and M21 additionally inhibit activin A receptor type 1 (ACVR1), also known as activin receptor like kinase 2 (ALK2), which produces subsequent inhibition of liver hepcidin expression and increased iron availability resulting in increased red blood cell production. MF is a myeloproliferative neoplasm associated with constitutive activation and dysregulated JAK signaling that contributes to inflammation and hyperactivation of ACVR1. JAK signaling recruits and activates STAT (signal transducers and activation of transcription) proteins resulting in nuclear localization and subsequent regulation of gene transcription.

Side Effects

Adverse effects associated with the use of Ojjaara may include, but are not limited to, the following:

• thrombocytopenia
• hemorrhage
• bacterial infection
• fatigue
• dizziness
• diarrhea
• nausea

Clinical Trial Results

The FDA approval of Ojjaara was based on data from the pivotal MOMENTUM study and a subpopulation of adult patients with anemia from the SIMPLIFY-1 phase III trial. 

MOMENTUM was designed to evaluate the safety and efficacy of momelotinib versus danazol for the treatment and reduction of key manifestations of myelofibrosis in an anemic, symptomatic, JAK inhibitor-experienced population. The MOMENTUM trial met all its primary and key secondary endpoints, demonstrating statistically significant response with respect to constitutional symptoms, splenic response and transfusion independence, in patients treated with momelotinib versus danazol. 

SIMPLIFY-1 was designed to evaluate the efficacy and safety of momelotinib versus ruxolitinib in myelofibrosis patients who had not received a prior JAK-inhibitor therapy. Safety and efficacy results for SIMPLIFY-1 were based upon a subset of patients with anemia. The efficacy of Ojjaara was based on spleen volume response (reduction by 35% or greater). A numerically lower percent of patients treated with Ojjaara (25%) achieved a Total Symptom Score reduction of 50% or more at Week 24 compared with ruxolitinib (36%).