Swedish Orphan Biovitrum AB (Stockholm: SOBI), operating through its North American affiliate Sobi North America, announced that the US FDA has granted Fast Track Designation to pacritinib (Vonjo), a dual IRAK1/JAK2 small molecule kinase inhibitor, for the treatment of VEXAS syndrome — a systemic autoinflammatory and hematologic disorder for which no therapy is currently approved.
VEXAS syndrome (Vacuoles in blood-cell precursors, E1 enzyme, X-linked, Autoinflammatory, Somatic) was first described in 2020 and is characterized by overlapping hematologic and inflammatory features across multiple organ systems. Most immunomodulators fail to control the disease, leaving patients dependent on moderate to high doses of glucocorticoids.
Sobi is evaluating pacritinib in VEXAS through the PAXIS trial (NCT06782373), a Phase II randomized, multicenter, double-blind, placebo-controlled, dose-finding study followed by an open-label period. The trial, which the company said is the first randomized study conducted in this condition, is designed to assess efficacy and safety in preventing disease flares following glucocorticoid tapering. Topline data are expected in 2027.
The mechanistic rationale for pacritinib in VEXAS rests on its inhibition of IRAK1, which mediates innate immune and inflammatory signaling, JAK2, which drives cytokine and hematopoietic pathway activation, and ACVR1 — all implicated in the autoinflammatory and myeloid pathology that characterizes the syndrome.