Kidney Week

Abstract: FR-OR60

Efficacy and Safety of Ravulizumab in IgAN: Week 50 Results from a Phase 2 Randomized Controlled Trial

Session Information

• IgA Nephropathy: New Therapies and Insights
  October 25, 2024 | Location: Room 6D, Convention Center
  Abstract Time: 05:10 PM - 05:20 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Tumlin, James A., Emory University, Atlanta, Georgia, United States

James A. Tumlin, MD, FASN

• Lafayette, Richard A., Stanford University, Stanford, California, United States

Richard A. Lafayette, MD

• Barratt, Jonathan, University of Leicester, Leicester, United Kingdom

Jonathan Barratt, MBChB, PhD

• Wu, Mai-Szu, Taipei Medical University, Taipei, Taiwan

Mai-Szu Wu, MD

• Kim, Sung Gyun, Hallym University Sacred Heart Hospital, Anyang, Gyeonggi-do, Korea (the Republic of)

Sung Gyun Kim, MD, PhD

• Kaufeld, Jessica Katharina, Medizinische Hochschule Hannover, Hannover, Niedersachsen, Germany

Jessica Katharina Kaufeld, MD

• Huang, Shih-Han S., London Health Sciences Centre, London, Ontario, Canada

Shih-Han S. Huang, MD, PhD

• Alamartine, Eric, Hopital Nord Service de Nephrologie, Saint Priest en Jarez, Auvergne-Rhône-Alpes , France

Eric Alamartine, MD, PhD

• Pérez Valdivia, Miguel Angel, Hospital Universitario Virgen del Rocio, Sevilla, Andalucía, Spain

Miguel Angel Pérez Valdivia, MD

• Rice, Kara, Alexion Pharmaceuticals Inc, Boston, Massachusetts, United States

Kara Rice, MS

• Kateifides, Andreas, Alexion Pharmaceuticals Inc, Boston, Massachusetts, United States

Andreas Kateifides

• Garlo, Katherine, Alexion Pharmaceuticals Inc, Boston, Massachusetts, United States

Katherine Garlo, MD

• Roccatello, Dario, Universita degli Studi di Torino, Torino, Piemonte, Italy

Dario Roccatello, MD

Background

In IgA nephropathy (IgAN), terminal complement pathway activation contributes to inflammation and glomerular damage. Early and meaningful reductions in proteinuria were demonstrated with complement C5 inhibitor ravulizumab (RAV) in the phase 2 SANCTUARY trial (NCT04564339) through 26wks; efficacy and safety data through 50wks are presented.

Methods

Adults with primary IgAN, proteinuria ≥1 g/d, eGFR ≥30 mL/min/1.73 m², and on stable/optimal RASi were randomized 2:1 to RAV or placebo (PBO) (IV; q8w) for 26wks. At wk26, PBO group switched to open label RAV (PBO-RAV). Primary endpoint: change in proteinuria at 26wks; secondary endpoints: change in proteinuria and eGFR at 50wks. Safety and PK/PD were assessed.

Results

Of 66 randomized patients (pts; RAV n=43; PBO n=23), 64 completed wk50. In RAV and PBO arms, respective baseline (BL) UPCR was 1.7 and 1.8 g/g; BL eGFR was 76.0 and 70.4 mL/min/1.73 m². At 26wks, a –33.2% treatment effect on UPCR was demonstrated with RAV vs PBO (p=0.0011). At 50wks, RAV pts had a 41.1% reduction from BL in UPCR. PBO-RAV pts had a 43.1% decrease in UPCR from BL (wk0) to wk50 (Figure). Annualized eGFR slope in RAV pts was –1.4 at 26wks and –2.3 at 50wks and in PBO-RAV pts was –6.7 and –4.1 at 26 and 50wks, respectively. The majority of AEs were mild; no serious treatment-related AEs, discontinuations from AEs, or deaths occurred.

Conclusion

Treatment with RAV was well-tolerated and demonstrated early and sustained proteinuria reduction through ~1 year, and after wk26 switch from PBO to RAV.

Funding

• Commercial Support – Alexion, AstraZeneca Rare Disease