JAK inhibitor for VEXAS syndrome gets orphan drug designations

GSK’s momelotinib, a JAK inhibitor with a differentiated mechanism of action, has received Orphan Drug Designation (ODD) from the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) for the treatment of VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome.  

VEXAS syndrome is a clonal myeloid disorder with rheumatologic and haematologic clinical features. It is a highly symptomatic progressive condition with a 30-40% five-year mortality rate and no currentlyapproved treatment options.  

The ODDs were supported by retrospective case studies demonstrating that JAK inhibitors may be an effective therapeutic option for VEXAS syndrome as well as evidence from a case report that indicated potential clinical benefit from treatment with momelotinib, including improvements in symptoms and VEXAS-related inflammation and haematological manifestations. 

The planned Phase II/III ATLAS trial will evaluate momelotinib’s efficacy and safety in VEXAS syndrome and will support planned global regulatory submissions. The study design was presented at the 2026 European Hematology Association (EHA) Congress taking place 11-14 June.  

Momelotinib (Ojjaara/Omjjara) is currently approved in the US for the treatment of intermediate- or high-risk myelofibrosis in adults with anaemia. It is also approved in the EU and UK for the treatment of myelofibrosis with disease-related splenomegaly or symptoms in adults with moderate to severe anaemia, and in Japan for the treatment of myelofibrosis.   

It has a differentiated mechanism of action, with inhibitory ability along three key signalling pathways: Janus kinase (JAK) 1, JAK2, and activin A receptor, type I (ACVR1). Inhibition of JAK1 and JAK2 may improve constitutional symptoms and splenomegaly. Additionally, inhibition of ACVR1 leads to a decrease in circulating hepcidin levels, potentially contributing to anaemia-related benefit. 

VEXAS syndrome is a recently classified clonal myeloid disorder with rheumatologic and haematologic clinical features that is characterised by a broad spectrum of inflammatory manifestations. 

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