GSK's Momelotinib Receives Orphan Drug Designations in US and EU for VEXAS Syndrome
核心洞察
GSK's momelotinib, a differentiated JAK1 (搜索)/JAK2 (搜索)/ACVR1 (搜索) inhibitor, has been granted Orphan Drug Designation by both the FDA and EMA for VEXAS syndrome (搜索), a rare haemato-inflammatory condition with no approved treatments.
VEXAS syndrome (搜索) carries a 30-40% five-year mortality rate and predominantly affects men over 50, with diagnosis confirmed through UBA1 (搜索) gene mutation testing.
The phase II/III ATLAS trial is underway to evaluate momelotinib's efficacy and safety in VEXAS, with study design to be presented at the 2026 EHA Congress.
GSK plc today announced that momelotinib, a JAK inhibitor with a differentiated mechanism of action, has received Orphan Drug Designation (ODD) from both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome. The announcement, issued 12 June 2026 from London, marks a significant regulatory milestone for a condition that currently has no approved treatment options.
VEXAS syndrome (搜索) is a recently classified clonal myeloid disorder with rheumatologic and haematologic clinical features. It is a highly symptomatic, severe, progressive condition with a poor prognosis, carrying a 30-40% five-year mortality rate. The syndrome predominantly affects men aged over 50 years, as the UBA1 (搜索) gene mutation responsible for the condition is located on chromosome X and is somatic in nature. Diagnosis is confirmed by genetic testing for the UBA1 gene mutation.
Supporting Evidence for the Designations
The ODDs were supported by retrospective case studies demonstrating that JAK inhibitors may be an effective therapeutic option for VEXAS syndrome (搜索), as well as evidence from a case report that indicated potential clinical benefit from treatment with momelotinib. According to the case report, improvements were observed in symptoms and VEXAS-related inflammation and haematological manifestations. Orphan Drug Designations are granted by regulators to support the development efforts and regulatory evaluations of new medicines that have the potential to treat or prevent rare disorders.
The ATLAS Trial
The planned phase II/III ATLAS trial will evaluate momelotinib's efficacy and safety in VEXAS syndrome (搜索) and will support planned global regulatory submissions. The study design will be presented at the 2026 European Hematology Association (EHA) Congress taking place 11-14 June. The trial is part of momelotinib's ongoing development programme evaluating its potential across multiple haematological conditions.
Momelotinib's Differentiated Mechanism
Momelotinib has a differentiated mechanism of action, with inhibitory ability along three key signalling pathways: Janus kinase (JAK) 1, JAK2 (搜索), and activin A receptor, type I (ACVR1 (搜索)). Inhibition of JAK1 (搜索) 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.
Momelotinib (marketed as Ojjaara/Omjjara) is currently approved in the US for the treatment of intermediate- or high-risk myelofibrosis (搜索) 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.
Clinical Features of VEXAS Syndrome (搜索)
VEXAS syndrome (搜索) is characterised by a broad spectrum of inflammatory manifestations such as prolonged fever, weight loss, uveitis, relapsing chondritis, neutrophilic dermatosis, vasculitis and lung involvement. Additionally, patients often present with haematologic complications, including macrocytic anaemia, thrombocytopenia and progressive bone marrow failure, which can evolve to haematologic malignancy. There are currently no approved treatments for VEXAS syndrome, underscoring the significance of these regulatory designations for patients affected by this life-threatening condition.