In short
Momelotinib is a Janus kinase (JAK) inhibitor authorised in the European Union as the medicine Omjjara for adults with myelofibrosis and moderate to severe anaemia. It is also being studied in a Phase 1 clinical trial for unresectable stage III or stage IV cutaneous melanoma, where it is given together with the checkpoint inhibitors nivolumab or pembrolizumab. The trial plans to enrol 105 participants and is currently authorised.
Key points
- Momelotinib is authorised in the EU as Omjjara for adults with myelofibrosis and moderate to severe anaemia.
- It blocks a group of enzymes called Janus kinases (JAKs), which are involved in blood cell production and inflammation.
- A Phase 1 trial is studying momelotinib combined with nivolumab or pembrolizumab in advanced cutaneous melanoma.
- The melanoma trial plans to enrol 105 participants and is currently authorised.
- Omjjara is taken as a tablet by mouth once daily.
- Momelotinib was designated an orphan medicine for myelofibrosis.
What is momelotinib?
Momelotinib is a Janus kinase (JAK) inhibitor. It is the active substance in the medicine Omjjara, which is authorised for use in the European Union. Omjjara is used to treat splenomegaly (an enlarged spleen) or other disease-related symptoms in adults who have myelofibrosis and moderate to severe anaemia, meaning low levels of red blood cells. Myelofibrosis is a disease in which the bone marrow becomes very dense and rigid and produces abnormal, immature blood cells. The medicine is available as 100 mg, 150 mg and 200 mg film-coated tablets.
How does momelotinib work?
Momelotinib works by blocking a group of enzymes, or proteins, known as Janus kinases (JAKs). These enzymes are involved in the production and growth of blood cells. In myelofibrosis, there is too much JAK activity, which leads to the abnormal production of blood cells and inflammation. As a result, scar tissue replaces the bone marrow, causing blood cells to be produced in other organs. By blocking JAKs, momelotinib aims to reduce this abnormal blood cell production and the symptoms it causes.
Which conditions is it used or studied for?
- Myelofibrosis with moderate to severe anaemia — Omjjara is authorised for adults with an enlarged spleen or other disease-related symptoms in three types of myelofibrosis: primary myelofibrosis (also known as chronic idiopathic myelofibrosis), post-polycythaemia vera myelofibrosis, and post-essential thrombocythaemia myelofibrosis.
- Unresectable stage III or stage IV cutaneous melanoma — a Phase 1 clinical trial is studying momelotinib in combination with the checkpoint inhibitors nivolumab or pembrolizumab in this type of advanced skin cancer.
- EGFR-mutated, tyrosine kinase inhibitor-naive metastatic non-small cell lung cancer — a published Phase 1b study has investigated momelotinib together with erlotinib in this form of lung cancer.
How is momelotinib given?
Omjjara is available as a tablet to be taken by mouth once daily. The medicine comes in three strengths: 100 mg, 150 mg and 200 mg film-coated tablets. Treatment with Omjjara must be started and monitored by doctors experienced in the use of cancer medicines, and the doctor may reduce the dose, interrupt treatment or stop it altogether if the patient has certain side effects.
What do the clinical trials show?
One registered clinical trial is currently listed for momelotinib in the EU Clinical Trials Information System. This is a Phase 1 trial in unresectable stage III or stage IV cutaneous melanoma, with a planned enrolment of 105 participants. The trial is authorised, meaning it has received regulatory approval to begin.
The trial has two parts. In Phase Ib, researchers are evaluating the safety and tolerability of momelotinib in combination with an anti-PD-1 antibody — either nivolumab or pembrolizumab — in patients with cutaneous melanoma. They are also determining the maximum tolerated dose (MTD) and the recommended Phase II dose (RP2D). In Phase II, the trial will evaluate the preliminary anti-tumour activity of the combination at 6 months, measured by the objective response rate (ORR), which is the proportion of patients whose tumours shrink or disappear according to RECIST 1.1 criteria.
The primary outcomes being measured include the incidence and severity of treatment-emergent adverse events, serious adverse events, and clinically significant laboratory abnormalities. The trial also records complete responses (CR), partial responses (PR), stable disease (SD) and progressive disease (PD) at radiological response evaluations 6 months after the first dose.
What side effects are known?
The European Medicines Agency notes that the doctor may reduce the dose, interrupt treatment or stop it altogether if the patient has certain side effects, but the specific side effects are described in the package leaflet and are not detailed in the sources provided here.