Abstract: PO2541
Long-Term Phase 2 Efficacy of the MASP-2 Inhibitor Narsoplimab for Treatment of Severe IgA Nephropathy
Session Information
- Late-Breaking Clinical Trials Posters
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1203 Glomerular Diseases: Clinical, Outcomes, and Trials
Authors
- Lafayette, Richard A., Stanford University, Stanford, California, United States
- Carroll, Kevin, KJC Statistics Ltd., Cheshire, United Kingdom
- Barratt, Jonathan, University of Leicester, Leicester, United Kingdom
Group or Team Name
- On behalf of the ALC Steering Committee
Background
IgA nephropathy (IgAN) is a glomerular disease in which the lectin pathway of complement is activated following mesangial deposition of IgA immune complexes. Narsoplimab (OMS721) inhibits mannan-binding lectin-associated serine protease-2 (MASP-2), the effector enzyme of the lectin pathway.
Methods
A staged Phase 2 study (NCT02682407) enrolled adult patients with severe IgAN. Substudy 1 was a single-arm open-label study of 12 weekly IV infusions of narsoplimab and tapered corticosteroids. In substudy 2, corticosteroid-free patients were randomized 1:1 to receive weekly IV narsoplimab or vehicle infusions for 12 weeks followed by open-label extension. The primary endpoint was safety and tolerability of narsoplimab. Key secondary endpoints were 24-hour urine protein excretion (UPE) and estimated glomerular filtration rate (eGFR) assessed by time-weighted average regression analysis after up to 35 months follow-up. Patients from the Leicester Renal Unit IgA Nephropathy Registry with similar disease burden and matched baseline UPE and eGFR values were used as the comparator group.
Results
This high-risk population with advanced IgAN at enrollment had a median disease duration of 6.9 yrs (range 0.4–27.5). Baseline risk factors included hypertension (10/12, 83%), obesity (7/12, 58%; median BMI 32.5 kg/m2; range 24.4–44.3), excessive proteinuria (median UPE of 4.2 g/24 hr; range 1.5–11.9), and kidney dysfunction (median eGFR of 40.8 mL/min/1.73m2; range 25.4–76.5). 12 patients participated in the dosing extension phase and were followed for a median of 22 months. Patients received median 1 course of 12 weekly doses of narsoplimab per year (range 0.7–2.5 courses), with 58% (7/12) receiving ≤1 course per year. eGFR rate of decline was 5.2 (±2.1) mL/min/yr vs 8.6 (±3.7) mL/min/yr in the Leicester IgAN control cohort, suggesting better eGFR stability in the patient population. Over 3 years, eGFR improved in 25% (3/12) of patients. UPE decreased 38% from baseline through the follow-up period. Narsoplimab was well tolerated with no treatment-related serious adverse events reported.
Conclusion
In this Phase 2 study, narsoplimab was well tolerated. Treatment in patients with severe IgAN resulted in proteinuria reduction and better renal protection via eGFR stability relative to a matched comparator group.
Funding
- Commercial Support –