PHASE 3 COMMODORE TRIALS OF CROVALIMAB IN PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH): IMPACT ON KIDNEY FUNCTION

Back

E-Poster

https://storage.unitedwebnetwork.com/files/1099/665b491a4d7019e17f5290875a7fcfb6.pdf

Abstract Title

First Name *

Rocio

Last Name *

Soldati

Co-author 1

Sasha Sreckovic sreckovic.sasha@gene.com Genentech, Ltd PD Safety Risk Management San Fransisco

Co-author 2

Cristian Brocchieri cristian.brocchieri@roche.com F. Hoffmann-La Roche Ltd. Hematology and Nephrology Rare Diseases Basel

Co-author 3

Patty Leon leon.patty@gene.com Genentech, Ltd PDH Rare Blood Disorders San Francisco, CA

Co-author 4

Nadiesh Balachandran nadiesh.balachandran@roche.com F. Hoffmann-La Roche Ltd. Signal Detection, BPO Basel

Co-author 5

Marianne Uguen marianne.uguen@roche.com F. Hoffmann-La Roche Ltd. Signal Detection, BPO Basel

Co-author 6

Simon Buatois simon.buatois@roche.com F. Hoffmann-La Roche Ltd. Pharmaceutical Sciences Basel

Co-author 7

Co-author 8

Co-author 9

Co-author 10

Co-author 11

Co-author 12

Co-author 13

Co-author 14

Co-author 15

Introduction

Complement inhibition is the standard of care in PNH and atypical hemolytic uremic syndrome (aHUS). Crovalimab (crova), a C5 inhibitor, enables rapid, complete, and sustained C5 inhibition with subcutaneous self-administration in patients (pts) with PNH who are complement inhibitor naive or switching to crova. Crova has non-inferior efficacy vs eculizumab (ecu) and a safety profile consistent with that of other C5 inhibitors. Here we evaluate kidney function in the Phase 3 pts.

Methods

Pts with PNH received crova or ecu in one of the Phase 3 studies: global, randomized COMMODORE 1 (treatment-switch pts) and COMMODORE 2 (naive pts), or China-based, single-arm COMMODORE 3 (naive pts). In COMMODORE 1 and 2, pts receiving ecu could switch to crova after the primary treatment period. Data were pooled for safety and kidney function evaluation.

Results

111 pts received ecu and 377 crova (192 naive, 185 switched to crova at study initiation or after primary period). Shifts in serum creatinine of ≥2 grade from baseline (BL) occurred in 4.5% (5/111) of ecu pts vs 6.9% (26/377) of crova pts (8.3% [16/192] of C5 naive vs 5.4% [10/185] of switch pts; Table). Post-BL grade 3/4 shifts occurred in 1 ecu pt (BL: grade 2), 1 naive pt (BL: grade 0), and 4 switch pts (BL: grade 0). Shifts occurred much later than the onset of ecu-C5-crova immune complexes, suggesting the shifts were unrelated to switching. Urine protein, albumin, and creatinine levels were not concerning. Type 3 hypersensitivity reactions, associated with complexes, occurred in 18% (33/185; 21 grade 1-2, 12 grade 3) of switch pts.

Conclusions

Serum creatinine shifts were comparable between ecu pts and pts who changed from ecu to crova or stayed on crova. Overall, the crova Phase 3 data show that the risk/benefit profile of crova is favorable in PNH and no new safety signals, including for kidney function, were observed. Crova is being evaluated for aHUS in the ongoing COMMUTE-a (NCT04861259) and COMMUTE-p (NCT04958265) studies.

This abstract was previously presented at ASN Kidney Week 2023.

E-Poster Format Requirements

PDF file
Layout: Portrait (vertical orientation)
One page only (Dim A4: 210 x 297mm or PPT)
E-Poster can be prepared in PowerPoint (one (1) PowerPoint slide) but must be saved and submitted as PDF file.
File Size: Maximum file size is 2 Megabytes (2 MB)
No hyperlinks, animated images, animations, and slide transitions
Language: English
Include your abstract number
E-posters can include QR codes, tables and photos