The US Food and Drug Administration (FDA) has granted approval to Ojjaara (momelotinib), a Janus kinase (JAK) inhibitor by GlaxoSmithKline (GSK), as the primary treatment for adults with intermediate or high-risk myelofibrosis experiencing anemia.
This includes those with primary myelofibrosis or secondary forms such as post-polycythemia vera and post-essential thrombocythemia, irrespective of prior treatments.
Myelofibrosis is a rare blood cancer that affects around 25,000 patients in the US. It is marked by scar tissue buildup in the bone marrow. Such fibrosis often diminishes various blood cell counts, particularly red blood cells, resulting in anemia.
Traditional treatments for myelofibrosis-associated anemia have sought heightened efficacy as earlier JAK inhibitors have been linked to myelosuppressive effects, which intensify anemia and impede oxygen distribution.
Ojjaara stands out as the sole approved drug for myelofibrosis patients that effectively targets primary symptoms, encompassing anemia, constitutional symptoms and splenomegaly (enlarged spleen).
“The vast majority of myelofibrosis patients eventually develop anemia, causing them to discontinue treatments and require transfusions. Given this high unmet need, we are proud to add Ojjaara to our oncology portfolio and address a significant medical need in the community. We look forward to helping improve outcomes in this difficult-to-treat blood cancer,” said Nina Mojas, Senior Vice President, Oncology Global Product Strategy, GSK, in the company’s press release.
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What Is Myelofibrosis?
As defined by the National Cancer Institute, primary myelofibrosis involves the build-up of abnormal blood cells and fibrous tissue within the bone marrow. The bone marrow is a tissue hub responsible for producing various blood cells, including red blood cells, white blood cells and platelets. It is also supported by a fibrous network. In primary myelofibrosis, many blood stem cells transform into immature blood cells, known as blasts, which fail to mature correctly.
Concurrently, the fibrous tissue in the bone marrow substantially thickens, much like scar tissue, which restricts the capacity of the blood-forming tissues to generate new blood cells. Consequently, there’s a gradual decline in the bone marrow’s blood cell production. To counteract this reduction, the liver and spleen step in to produce blood cells.
At the time of diagnosis, about one-third of myelofibrosis patients exhibit anemia. Over time, this condition manifests in nearly all patients. Anemia’s emergence stems from a multifaceted combination of factors, some of which are not entirely comprehended. The JAK-STAT pathway’s persistent activation and the disruption of inflammatory cytokine production inhibit erythropoiesis in the bone marrow. Additionally, an enlarged spleen, which traps and destroys circulating red blood cells, contributes to anemia in myelofibrosis patients.
Mechanism of Action of Ojjaara
Momelotinib, a small-molecule oral kinase inhibitor, effectively inhibits three crucial signaling pathways: JAK 1, JAK2 and activin A receptor, type I (ACVR1).
The inhibition of JAK1 and JAK2 helps relieve constitutional symptoms and diminish splenomegaly, while directly inhibiting ACVR1 decreases circulating hepcidin levels, potentially aiding in the alleviation of anemia in myelofibrosis patients.
Efficacy and Safety of Ojjaara (Momelotinib)
The safety and efficacy of Ojjaara were primarily grounded in the results of two key clinical trials: MOMENTUM and SIMPLIFY-1.
The international, double-blind, Phase III MOMENTUM study engaged patients from 107 sites in 21 countries. As detailed in The Lancet, compared to danazol, Ojjaara (momelotinib) showed significant improvements in myelofibrosis symptoms, anemia measures and spleen response, all while maintaining a favorable safety record.
On the other hand, the Phase III SIMPLIFY-1 trial compared momelotinib’s effectiveness and safety against ruxolitinib for myelofibrosis patients without prior JAK inhibitor treatments. As reported in the Journal of Clinical Oncology, treatments with momelotinib correlated with fewer transfusion needs.
The most common adverse reactions in these clinical trials were thrombocytopenia, hemorrhage, bacterial infection, fatigue, dizziness, diarrhea and nausea.
What Is the Price of Ojjaara?
The wholesale acquisition cost of Ojjaara will be $26,900 for a bottle of 30 tablets.
Other New and Promising Drugs for Myelofibrosis
Ojjaara is the fourth JAK inhibitor to gain FDA approval for myelofibrosis.
Several other drugs and combination regimens are in the pipeline for myelofibrosis. For instance, BMS’ luspatercept is currently in Phase II studies. Kartos Therapeutics’ navetmadlin, an HDM2 (human double-minute homolog 2) inhibitor, has shown promise in Phase II studies and is now in the Phase III BOREAS trial for patients with relapsed/refractory myelofibrosis.
Imetelstat, a telomerase inhibitor under development by the Geron Corporation, has demonstrated efficacy in Phase II studies and is currently in the Phase III IMpactMF trial, targeting myelofibrosis patients who are resistant to JAK inhibitors.
Other drugs under investigation for myelofibrosis include:
- Sumitomo Pharma Oncology’s TP-3654 (PIM-1 inhibitor).
- Pharmaxis’ PXS5505 (pan-lysyl oxidase inhibitor).
- Telios Pharma’s TL-895 (tyrosine kinase inhibitor).
- Karyopharm Therapeutics’ selinexor (selective inhibitor of nuclear export, SINE, inhibitor).
- Imago BioSciences’ bomedemstat (lysine-specific demethylase 1, LSD1, inhibitor).