GSK’s momelotinib receives FDA and EMA Orphan Drug Designation for VEXAS syndrome, supporting the Phase II/III ATLAS trial in a rare disorder with no approved treatments.
Written By: Kalyani Boharapi,
M.Pharm (Reg. Affairs)
Reviewed By: Pharmacally Editorial Team
GSK has received Orphan Drug Designation (ODD) from both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for momelotinib in the treatment of VEXAS syndrome, a rare haemato-inflammatory disorder with no approved therapies.
The designations provide incentives including regulatory guidance, fee reductions, and potential market exclusivity, highlighting the importance of advancing new treatment options for rare diseases with significant unmet medical need.
Expanding Development Beyond Myelofibrosis
The regulatory decisions mark an important step in expanding momelotinib’s clinical development beyond its established role in myelofibrosis. Retrospective studies have suggested that Janus kinase (JAK) inhibitors may provide clinical benefit in patients with VEXAS syndrome, while a published case report indicated potential activity with momelotinib, including improvements in inflammatory symptoms and haematologic manifestations.
The orphan designations support ongoing efforts to evaluate momelotinib as a potential treatment option for VEXAS syndrome, where no approved therapies currently exist.
Disease Context and Clinical Urgency
VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) is a recently identified clonal myeloid disorder caused by acquired mutations in the UBA1 gene. The disease primarily affects men over the age of 50 and combines severe systemic inflammation with progressive bone marrow dysfunction.
Patients frequently experience recurrent fevers, weight loss, relapsing chondritis, vasculitis, skin inflammation, pulmonary involvement, and other inflammatory complications. Haematologic manifestations are also common and include macrocytic anaemia, thrombocytopenia, and progressive marrow failure, which can evolve into haematologic malignancies. Reported five-year mortality rates of 30% to 40% underscore the urgent need for effective therapies.
Mechanism of Action
Momelotinib is a differentiated JAK inhibitor that targets JAK1, JAK2, and activin A receptor type 1 (ACVR1). Inhibition of JAK1 and JAK2 may reduce inflammatory signalling and disease-related symptoms, while ACVR1 inhibition lowers circulating hepcidin levels, a mechanism associated with improvements in anaemia.
This dual mechanism may address both inflammatory manifestations and anaemia, two major clinical features of VEXAS syndrome.
Clinical Development: ATLAS Trial
GSK is advancing the global Phase II/III ATLAS trial (NCT07569081) to evaluate the efficacy and safety of momelotinib in patients with VEXAS syndrome. The study represents one of the most advanced interventional programmes currently underway for the disorder and is expected to support planned global regulatory submissions.
Details of the trial design are being presented at the 2026 European Hematology Association (EHA) Congress, where investigators will outline the study’s approach to assessing momelotinib’s potential clinical benefit in this underserved patient population.
Strategic Positioning Across Haematology
Momelotinib is already marketed as OJJAARA in the United States and OMJJARA in Europe and the United Kingdom for certain patients with myelofibrosis and anaemia. The therapy is also approved in Japan for the treatment of myelofibrosis.
The orphan designations support GSK’s efforts to expand momelotinib beyond myelofibrosis into additional haematologic disorders with significant unmet need, further broadening the drug’s development programme across rare and serious diseases.
Potential Treatment for VEXAS
With no approved therapies currently available for VEXAS syndrome, the FDA and EMA orphan designations represent an important step in developing one of the first targeted treatment approaches for the disease.
The ATLAS trial will be closely followed by clinicians, researchers, and regulators as evidence emerges on whether momelotinib can address both the inflammatory and haematologic manifestations that drive the burden of this severe and often life-threatening disorder.
Reference
GSK’s momelotinib granted Orphan Drug Designations in the US and EU for VEXAS syndrome | GSK
About the Writer
Kalyani Boharapi (LinkedIn) is a pharmacy professional and healthcare writer currently pursuing an M.Pharm in Regulatory Affairs at Dr. D. Y. Patil College of Pharmacy, with interests in pharmaceutical regulations, drug development, and healthcare innovation. She has academic exposure to dossier preparation, scientific writing, and regulatory documentation. Kalyani has also completed certification courses in Generative AI, AI in Pharma, and Bioinformatics, and actively participates in pharmaceutical conferences to stay updated with emerging trends and advancements in the healthcare and pharmaceutical industry.