Kidney Week

Abstract: FR-PO0812

Efficacy and Safety of ALXN2050 in IgAN: Results of a Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial

Session Information

• Glomerular Clinical Trials: From Data to Impact
  November 07, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Roccatello, Dario, San Giovanni Bosco Hub Hospital, ASL Città di Torino and Department of Clinical and Biological Sciences of the University of Turin, Turin, Italy

Dario Roccatello, MD

• Norouzi, Sayna, Loma Linda University, Loma Linda, California, United States

Sayna Norouzi, MD, FASN

• El Kossi, Mohsen, Doncaster Royal Infirmary, Doncaster, United Kingdom

Mohsen El Kossi, MD, MBChB

• Uriol Rivera, Miguel, Son Espases University Hospital, Glomerular Diseases Unit, Palma, Spain

Miguel Uriol Rivera, MD, PhD

• Fischereder, Michael, Medizinische Klinik und Poliklinik IV, LMU Klinikum, LMU Munich, Munich, Germany

Michael Fischereder, MD

• Silva, Arnold L., Boise Kidney and Hypertension Institute, Meridian, Idaho, United States

Arnold L. Silva, MD, PhD

• Assady, Suheir, Rambam Health Care Campus, Haifa, Israel

Suheir Assady, MD, PhD

• Souza, Pedro Augusto Macedo, Santa Casa de Belo Horizonte, Centro de Nefrologia, Belo Horizonte, MG, Brazil

Pedro Augusto Macedo Souza, MD

• Youssef, Wahid, Clinical Development, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States

Wahid Youssef, MD

• Singh, Anika T., Clinical Development, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States

Anika T. Singh, MBChB, MS

• Yu, Ji, Biostatistics, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States

Ji Yu

• Sullivan, Christopher, Clinical Operations, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States

Christopher Sullivan

• Zodiatis, Alexander, Global Patient Safety, Alexion, AstraZeneca Rare Disease, New Haven, Connecticut, United States

Alexander Zodiatis, DO

• Carrillo Infante, Cynthia, Global Patient Safety, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States

Cynthia Carrillo Infante, MD, PhD

• Hamel, Brieanna, Clinical Development, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States

Brieanna Hamel

• Farag, Youssef MK, Clinical Development, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States

Youssef MK Farag, MD, PhD, MPH, FASN

• Cheung, Chee Kay, Mayer IgA Nephropathy Laboratories, Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom

Chee Kay Cheung, MBChB, PhD

Background

ALXN2050 (vemircopan) is an oral small molecule Factor D inhibitor of the complement alternative pathway. We report efficacy and safety of ALXN2050 in the IgA nephropathy (IgAN) cohort of a ph2 trial (NCT05097989) that also included lupus nephritis (LN).

Methods

In the initial evaluation period (IEP), patients (pts) with IgAN, urine protein (UP) ≥1 g/d, eGFR >30 mL/min/1.73m², and on stable RASi were randomized 3:1:3 to ALXN2050 180mg, ALXN2050 120mg, or placebo (PBO) BID for 26 weeks (W). Primary endpoint: % change in UP from baseline (BL) to W26 based on 24hr urine.

Results

Of 61 pts, 47 (77.0%) completed the IEP. At BL, mean UP and eGFR (ALXN2050 vs PBO) were 2.2 vs 2.1 g/d and 65.9 vs 70.6 mL/min/1.73m². At W26, % change in UP (ALXN2050 180mg vs PBO) was −26.2% vs −10.3%, yielding a relative treatment effect of −17.7% (90% CI: −37.5%, 8.3%); sensitivity analysis was similar. Relative treatment effect with ALXN2050 total was −18.6% (90% CI: −37.0%, 5.1%) (Table 1). Study dosing paused after an SAE in the LN cohort: jaundice and elevated liver enzymes reported as possibly related, with a fatal outcome consistent with acute hepatic failure. The trial was terminated as data interpretation post dosing re-initiation would be confounded. The majority of AEs (IgAN cohort) during IEP were mild and not related (Table 2). No serious treatment-related AEs or discontinuations from AEs occurred with ALXN2050. During the extension period, a pt on ALXN2050 180mg had an AE of liver enzyme elevation with positive rechallenge.

Conclusion

A non-statistically significant reduction in UP was observed with ALXN2050 180mg vs PBO. While ALXN2050 was generally well-tolerated in IgAN, a risk of liver enzyme elevation was identified from study-wide data review.

Funding

• Commercial Support – Alexion, AstraZeneca Rare Disease, Boston, MA, United States

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.20250j8aqeht