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Kidney Week

Abstract: SA-PO280

Phase 3 COMMODORE Trials of Crovalimab in Paroxysmal Nocturnal Hemoglobinuria (PNH): Impact on Kidney Function

Session Information

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

  • 2000 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

  • Sreckovic, Sasha, Genentech, Inc., San Fransisco, California, United States
  • Brocchieri, Cristian, F. Hoffmann-La Roche Ltd, Basel, Switzerland
  • Leon, Patty G., Genentech, Inc., San Fransisco, California, United States
  • Balachandran, Nadiesh, F. Hoffmann-La Roche Ltd, Basel, Switzerland
  • Uguen, Marianne, F. Hoffmann-La Roche Ltd, Basel, Switzerland
  • Buatois, Simon, F. Hoffmann-La Roche Ltd, Basel, Switzerland
Background

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 is 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 (gr) from 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 gr 3/4 shifts occurred in 1 ecu pt (BL: gr 2), 1 naive pt (BL: gr 0) and 4 switch pts (BL: gr 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 gr 1-2, 12 gr 3) of switch pts.

Conclusion

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.

Funding

  • Commercial Support – This study was funded by F. Hoffmann-La Roche, Basel, Switzerland