Abstract: TH-OR27
Safety and Efficacy of Felzartamab in Primary Membranous Nephropathy (PMN): Final Analysis of the M-PLACE Study
Session Information
- Glomerular Diseases: Clinical and Translational Studies
November 02, 2023 | Location: Room 103, Pennsylvania Convention Center
Abstract Time: 05:24 PM - 05:33 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Trials
Authors
- Rovin, Brad H., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
- Ronco, Pierre M., Sorbonne Universite, Paris, Île-de-France, France
- Wetzels, Jack F., Radboud Universiteit, Nijmegen, Gelderland, Netherlands
- Adler, Sharon G., Harbor-UCLA Medical Center, Los Angeles, California, United States
- Ayoub, Isabelle, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
- Han, Seung Hyeok, Yonsei University, Seoul, Seoul, Korea (the Republic of)
- Dudani, Jaideep, Human Immunology Biosciences Inc, South San Francisco, California, United States
- Gilbert, Houston N., Human Immunology Biosciences Inc, South San Francisco, California, United States
- Patel, Uptal D., Human Immunology Biosciences Inc, South San Francisco, California, United States
- Jauch-Lembach, Julia, MorphoSys AG, Planegg, Germany
- Faulhaber, Nicola, MorphoSys AG, Planegg, Germany
- Boxhammer, Rainer, MorphoSys AG, Planegg, Germany
- Haertle, Stefan, MorphoSys AG, Planegg, Germany
- Sprangers, Ben, Katholieke Universiteit Leuven Universitaire Ziekenhuizen Leuven Campus Gasthuisberg, Leuven, Flanders, Belgium
Background
PMN, a common cause of nephrotic syndrome with serious sequelae, is characterized by deposition of pathogenic autoantibodies forming immune complexes between podocytes and the basement membrane. Felzartamab (Felza), a fully human IgG1 anti-CD38 mAb, binds to CD38 antigen and depletes plasmablasts and plasma cells, the source of pathogenic aPLA2Rab.
Methods
M-PLACE (NCT04145440), a P1b/2a multi-national study, assessed safety and efficacy of felza in 2 adult cohorts with aPLA2R+ PMN requiring immunosuppressive therapy (IST). Cohort 1 (C1) enrolled newly diagnosed or relapsed patients and Cohort 2 (C2) enrolled IST-refractory patients. Nine infusions (16 mg/kg) were given over 5 months with a total observation period of 12 months.
Results
Among 31 patients (C1, n=18; C2, n=13) baseline characteristics include (Mean (SD)): Age 57.5 (11.8) yrs, serum aPLA2R titer 247.1 (259.3) U/mL, UPCR 6.4 (2.2) g/g, and serum albumin 26.8 (4.96) g/L. Most frequently reported TEAEs were infusion reactions in 9 patients (29.0%); 5 patients (16.1%) had serious TEAEs. Twenty-three patients (74%) achieved immunological response of > 50% aPLA2R reduction, with 8 (26%) achieving complete immunological response (aPLA2R changes shown in Fig. 1). Of the patients who received >5 Felza doses and no other IST, 7/15 (47%) patients in C1 and 2/11 (18%) patients in C2 achieved partial remission (UPCR reduction > 50%, UPCR < 3.0 g/g, and stable GFR) within the 12 month period. Consistent with the short period of follow-up, no patients achieved CR. Serum albumin increased in 11/15 (73%) patients in C1 and 7/10 (70%) patients in C2.
Conclusion
In high-risk patients with high unmet need (previously relapsing or refractory to IST, among the highest aPLA2R titer in a therapeutic clinical study to date), felza resulted in rapid, deep, and durable aPLA2R responses with associated improvements in proteinuria and serum albumin. Depleting CD20−/CD38+ plasma cells is a promising therapeutic strategy for treatment of PMN, including patients with high aPLA2R titers.
Funding
- Commercial Support – Human Immunology Biosciences Inc, MorphoSys AG