Kidney Week

Abstract: SA-PO278

Maintenance of Remission Following Completion of OMS721 Treatment in Patients with IgA Nephropathy (IGAN)

Session Information

• Clinical Glomerular Disorders: Vasculitis, C3G, IgAN
  November 04, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Glomerular

• 1005 Clinical Glomerular Disorders

Authors

• Block, Geoffrey A., Denver Nephrology, Denver, Colorado, United States

Geoffrey A. Block,

• Whitaker, Steve, Omeros Corporation, SEATTLE, Washington, United States

Steve Whitaker,

Background

The lectin pathway of complement has been implicated in the pathogenesis of several glomerulopathies including IgAN. OMS721 is a fully human monoclonal antibody that inhibits mannan-associated lectin-binding serine protease-2 (MASP-2), the effector enzyme of the lectin pathway. In a clinical trial, all OMS721-treated patients with IgAN achieved partial remission. These patients were followed after the trial. The duration of remission after OMS721 treatment was assessed.

Methods

The 4 IgAN patients are from an ongoing OMS721 Phase 2 clinical trial. All completed the trial. For inclusion, patients demonstrated 1) biopsy-diagnosed IgAN, 2) uACR > 0.6 g/g, 3) eGFR ≥ 30 mL/min/1.73 m², 4) controlled BP on stable ACEI/ARB treatment, and 5) a stable steroid dose ≥ 10 mg prednisone. All patients received OMS721 IV once weekly for 12 weeks. After OMS721 treatment, patients were followed for 6 more weeks in the trial. After trial completion patients have been followed by the investigator. In the trial endpoints were uACR and 24-hour proteinuria. In post-trial follow-up, uPCR was measured. Each uPCR value was converted to uACR by multiplying by 0.64. (Zhao, Clin J Am Soc Nephrol 2016;11:947-55)

Results

All patients achieved partial remission following OMS721 treatment. The mean age of the 3 females and 1 male was 42 years, 3 are Caucasian and one is Asian, the mean eGFR was 41 mL/min/1.73 m², and the mean entry steroid dose was 55 mg. Follow-up ranged from 2-9 months after the last OMS721 dose. During the trial the mean uACR decreased 77% (p = 0.026). Three patients maintained partial remission during available follow-up (54%, 79%, and 88% uACR decreases at 12, 12, and 5 months, respectively). One patient had 90% of baseline uACR at 7 months. Three patients also demonstrated improved eGFR by 7, 13, and 7 ml/min/1.73 m² during follow-up. The fourth patient’s eGFR was stable. All patients discontinued steroids. OMS721 was well tolerated. All adverse events were mild with headache and sinus congestion considered possibly related by the investigator.

Conclusion

Proteinuria significantly decreased in patients with IgAN during the 12-week treatment with OMS721. This reduction in proteinuria was maintained for up to 9 months after treatment completion. These data suggest that OMS721 may be efficacious in the treatment of IgAN and further study is warranted.