MYLOX-1 trial: LOXL2 inhibition for the treatment of MF

GB2064 is an investigational, potential first-in-class, oral lysyl oxidase-like 2 (LOXL2) inhibitor intended for the treatment of patients diagnosed with myelofibrosis who are ineligible, intolerant, or refractory to Janus kinase inhibitor therapy. LOXL2 plays a key role in myelofibrosis, contributing to the fibrotic progression of disease via mediation of collagen crosslinking in tissue fibrosis. Recently, topline results from the phase IIa MYLOX-1 trial (NCT04679870), investigating the safety and efficacy of GB2064, were released. We summarize the key points below.

Study design¹

• Phase IIa, open-label, single-arm study
• 1,000 mg orally, twice daily for 9 months
• Bone marrow biopsies at 3, 6, and 9 months
• The primary study endpoint was safety and tolerability
• Secondary endpoints were hematologic parameters and direct antifibrotic activity

Results¹

• N = 18
• In total, six of ten evaluable patients experienced ≥1 grade reduction in bone marrow fibrosis
  • All six of these patients also experienced stable hemoglobin, white blood cell, and platelet counts
• After 6 months, one patient experienced spleen volume reduction >35%
  • Another two patients experienced a >50% reduction in Total Symptom Score
  • Overall, one patient experienced an anemia response
• The safety profile was considered acceptable
  • In total, ten patients discontinued treatment due to adverse events (AEs) or disease progression
  • The most common AEs were gastrointestinal and manageable in most patients

Conclusion

These topline results indicate that GB2064 elicits strong antifibrotic activity and inhibition of LOXL2 in a difficult-to-treat patient population. The safety profile was considered acceptable, and AEs were manageable. Further analysis is ongoing to determine the potential of subsequent clinical trial stages.