Burixafor Demonstrates Superior CXCR4 Inhibition in Multiple Myeloma Stem Cell Mobilization

Exicure Inc. (XCUR) announced compelling phase 2 trial outcomes for Burixafor at the ASH Annual Meeting, showcasing a novel approach to hematopoietic stem cell mobilization. The announcement drove XCUR shares up significantly, closing previously at $5.33 and trading over 65% higher at $8.69 in overnight sessions.

Understanding the Clinical Challenge

Multiple myeloma, a malignant disorder affecting bone marrow plasma cells, remains a serious hematologic malignancy requiring aggressive intervention. The disease disrupts normal hematopoiesis, compromises immune function, and frequently results in skeletal deterioration and renal dysfunction. Standard therapeutic protocols in the United States mandate autologous hematopoietic cell transplantation (AHCT) following intensive chemotherapy regimens for newly diagnosed cases.

The cornerstone of AHCT success depends critically on efficient mobilization and collection of hematopoietic progenitor cells (HPCs). These stem cells must be extracted from bone marrow and redirected into peripheral circulation, where leukapheresis can harvest them for reinfusion post-transplant. This mobilization step has historically posed substantial clinical challenges, necessitating overnight pre-treatment with existing CXCR4 antagonists.

Burixafor’s Mechanism and Trial Design

Burixafor represents an investigational small-molecule CXCR4 inhibitor designed to disrupt CXCL12-CXCR4 receptor interactions on HPCs, facilitating rapid mobilization from marrow niches into bloodstream. The phase 2 study evaluated Burixafor administered alongside propranolol and granulocyte colony-stimulating factor, assessing their combined efficacy in improving CD34+ stem cell mobilization.

The primary efficacy endpoint focused on determining what proportion of participants would successfully collect at least 2 × 10^6 CD34+ cells per kilogram within two consecutive leukapheresis procedures.

Key Trial Outcomes

Results demonstrated robust clinical efficacy: 17 of 19 enrolled participants (89.5%) achieved the primary endpoint, collecting the required CD34+ cell dose within the initial two leukapheresis sessions. Only 2 participants required a third apheresis procedure to reach target cell quantities.

Among transplant recipients, neutrophil engraftment occurred at a median of 13 days post-infusion, while platelet recovery reached clinically safe thresholds within 17.5 days—timelines consistent with successful hematopoietic reconstitution.

Differentiated Kinetic Advantage

Burixafor demonstrated a distinctive pharmacokinetic profile compared to established CXCR4 antagonists currently in clinical use. Peak peripheral CD34+ levels emerged within approximately one hour following administration, enabling same-day mobilization and leukapheresis collection protocols—a substantial operational advantage.

Current FDA-approved CXCR4 inhibitors such as plerixafor and motixafortide necessitate overnight pre-treatment strategies, requiring patients to receive agents the evening prior to apheresis procedures. Burixafor’s rapid mobilization kinetics potentially streamlines clinical workflows and reduces patient burden.

Market Implications

The positive dataset positions Exicure’s investigational therapy as a potentially differentiated option within the CXCR4 antagonist therapeutic class, addressing a significant unmet need in stem cell mobilization efficiency. The clinical data translated into substantial market enthusiasm, reflected in the robust equity price movement.