Kidney Week

Abstract: FR-PO0824

Efficacy and Safety of ALXN2050 (Vemircopan) in Lupus Nephritis: Results of a 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

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

Sayna Norouzi, MD, FASN

• Belmont, H. Michael, New York University School of Medicine, New York, New York, United States

H. Michael Belmont, DrMed

• Su, Yu-Jih, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

Yu-Jih Su, MD, PhD

• Ye, Zhiming, Guangdongs Provincial People’s Hospital, Guangdong, China

Zhiming Ye

• Jones, Rachel B., Department of Medicine, University of Cambridge, Cambridge, United Kingdom

Rachel B. Jones, MD, MBBS

• Malvar, Ana, Organización Médica de Investigación, Buenos Aires, Argentina

Ana Malvar, 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

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

Cynthia Carrillo Infante, MD, PhD

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

Alexander Zodiatis, DO

• 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

Background

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

Methods

In the initial evaluation period (IEP), patients (pts) with LN with an active flare based on biopsy, requiring/receiving immunosuppression, UPCR ≥1 g/g from 24hr urine and eGFR >30 ml/min/1.73m² were randomized 3:1:3 to ALXN2050 180mg, ALXN2050 120mg, or placebo (PBO) BID for 26 weeks (W). Primary endpoint was % change in UPCR from baseline (BL) to W26 based on 24hr urine. Other endpoints included complete renal response, partial renal response, eGFR, and safety.

Results

Of 39 pts enrolled, 25 (64.1%) completed the IEP. Overall, mean BL UPCR and eGFR were 2.93 g/g and 99.9 mL/min/1.73m². Relative treatment effect on UPCR reduction with ALXN2050 180mg vs PBO was −6.0% (95% CI: −49.3%, 74.4%; p=0.87; Table 1) at W26. Results from dosing pause sensitivity analysis was similar. eGFR was stable over time and similar between ALXN2050 and PBO arms. Study dosing was paused after an SAE of 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. In the IEP, most AEs in ALXN2050 groups were grade 1-2 and considered unrelated to ALXN2050; 5 (21.7%) pts treated with ALXN2050 experienced an SAE (0 with PBO; Table 2).

Conclusion

There was no statistically significant difference in proteinuria reduction with ALXN2050 vs PBO. Liver enzyme elevation was determined to be an identified risk with ALXN2050 after study-wide data review.

Funding

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

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.20255apknkvm