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Abstract: TH-PO587

A Phase 1b, Single-Arm, Open-Label Study of Budoprutug, an Anti-CD19 Monoclonal Antibody with Enhanced Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC), in Primary Membranous Nephropathy

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Cortazar, Frank B., New York Nephrology, Vasculitis and Glomerular Center, Albany, New York, United States
  • Bonificio, William, Tenet Medicines, Scotch Plains, New Jersey, United States
  • Daryani, Naveen, Tenet Medicines, Scotch Plains, New Jersey, United States
  • Thomas, Stephen B., Tenet Medicines, Scotch Plains, New Jersey, United States
Background

Membranous nephropathy (MN) is characterized by a histologic pattern of injury caused by autoantibodies directed against podocyte antigens. Targeting B lymphocytes with anti-CD20 monoclonal antibodies has become a preferred therapy for primary MN, but this strategy fails to induce complete remission (CR) in most patients. Budoprutug is an anti-CD19 monoclonal antibody with a broader spectrum of B-cell depletion, including activity against CD19-positive plasmablasts and plasma cells. Here, we present the results of a Phase 1b, open label, dose escalation study of budoprutug in patients with primary MN.

Methods

Eligible patients had primary MN with a history of nephrotic syndrome, received maximally tolerated therapy with a renin-angiotensin system inhibitor for 6 months, and had a urine protein to creatinine ratio (UPCR) of > 2 g/g on two measurements during screening. Budoprutug was administered as 2 bi-weekly doses of 100 or 200 mg six months apart on Days 1,15,169, and 183. The primary objective was safety. Secondary objectives included B-cell levels, anti-phospholipase A2 receptor (anti-PLA2R) antibody (Ab) levels, and changes in proteinuria. The analysis was restricted to patients with at least 48 weeks of follow-up.

Results

Five patients met inclusion criteria, 3 of which were PLA2R Ab positive. All patients achieved complete B cell depletion, with 2 patients reconstituting B-cells before Week 24. Serologic remission was achieved in all anti-PLA2R Ab positive patients over a range of 5 to 18 weeks. Median baseline proteinuria was 4.2 g/g. Three patients achieved complete remission (UPCR ≤ 0.3 g/g, range, 40 to 48 weeks), with a fourth patient achieving a UPCR of 0.33 at week 48. All patients achieved a UPCR < 1 g/g and partial remission. Two patients with 72 week follow up achieved durable CRs ~18 months from initial dosing. Budoprutug was well tolerated with no drug-related serious or Grade ≥3 adverse events.

Conclusion

Treatment with budoprutug resulted in high rates of serologic and clinical remission, suggesting that CD19-targeted B-cell depletion may be a promising approach to the treatment of primary MN. These findings warrant larger studies to confirm the efficacy of budoprutug in MN.

Funding

  • Commercial Support – ValenzaBio, Acelyrin, Tenet Medicines