Kidney Week

Abstract: FR-OR102

HLX79 (E-602) Plus Rituximab Produces Fast and Durable Responses in Patients with Membranous Nephropathy

Session Information

• High-Impact Clinical Trials
  October 23, 2026 | Location: Bluebird Ballroom, Convention Center
  Abstract Time: 11:00 AM - 11:15 AM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Li, Zhilian, Guangdong Provincial People's Hospital, Guangzhou, China

Zhilian Li, MD, PhD

• Yu, Xueqing, Guangdong Provincial People's Hospital, Guangzhou, China

Xueqing Yu, MD, PhD

• Fan, Qiuling, Shanghai General Hospital, Shanghai, China

Qiuling Fan, MD

• Zuo, Li, Peking University People's Hospital, Beijing, China

Li Zuo, MD, PhD

• Wang, Deguang, The Second Hospital of Anhui Medical University, Hefei, China

Deguang Wang, MD

• Lv, Rong, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

Rong Lv, PhD

• Wang, Junxia, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan, China

Junxia Wang

• Ye, Zhiming, Guangdong Provincial People's Hospital, Guangzhou, China

Zhiming Ye

• Xu, Hui, Xiangya Hospital of Central South University, Changsha, China

Hui Xu, DrMed, DrPH

• Shao, Leping Shao,, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China

Leping Shao, Shao

• Yan, Yan, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China

Yan Yan, MD

• Mao, Huijuan, First Affiliated Hospital of Nanjing Medical University, Nanjing, China

Huijuan Mao, MD, PhD

• Zhong, Aimin, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi, China

Aimin Zhong, MBBS

• Chen, Cheng, Wuhan University Renmin Hospital, Wuhan, Hubei, China

Cheng Chen, MD, PhD

• Lu, Wanhong, First Affiliated Hospital of Medicine School, Xi'an Jiaotong University, Xi'an, China

Wanhong Lu, MD

• Cao, Lizhi, Palleon Pharmaceuticals Inc, Waltham, Massachusetts, United States

Lizhi Cao, PhD

• Brenner, Louis, Palleon Pharmaceuticals Inc, Waltham, Massachusetts, United States

Louis Brenner, MD

• Peng, Li, Palleon Pharmaceuticals Inc, Waltham, Massachusetts, United States

Li Peng, PhD

• Broderick, James W., Palleon Pharmaceuticals Inc, Waltham, Massachusetts, United States

James W. Broderick, MD

• Zang, Yunna, Shanghai Henlius Biotech, Inc., Shanghai, China

Yunna Zang, PharmD

• Wang, Yating, Shanghai Henlius Biotech, Inc., Shanghai, China

Yating Wang, MD

• Han, Lin, Shanghai Henlius Biotech, Inc., Shanghai, China

Lin Han

• Rovin, Brad, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Brad Rovin, MD, FASN

Background

Membranous nephropathy (MN) is the leading cause of autoimmune nephrotic syndrome in adults, with ~40% of patients progressing to fibrosis or kidney failure. Despite being recommended by KDIGO, rituximab (RTX) has a slow time to peak remission (~18–24 months), prolonging exposure to clinical risks. HLX79/E-602 (efgitasialase alfa), a first-in-class sialidase-Fc fusion protein, cleaves terminal sialic acid from cell-surface glycans to modulate sialoglycan-dependent macrophage activation, presumably by reducing pro-fibrotic CD163⁺ M2 macrophage burden as a single agent, and enhancing macrophage ADCP of B cells in combination with RTX.

Methods

This Phase 2 double-blinded RCT (NCT07038382) randomized 26 MN patients 3:1 (HLX79 + HLX01 [Rituximab (RTX) biosimilar] vs HLX01 alone) across three HLX79 dose cohorts (10, 20, 30 mg/kg). All patients received 4 weekly doses of HLX79 or placebo plus HLX01 375 mg/m² weekly. Primary endpoint was safety. Secondary endpoints were CR/PR rates at weeks 12, 24, 36, and 52 and change in proteinuria.

Results

HLX79 at 30 mg/kg plus RTX showed higher CR/PR rates than RTX alone at week 12 (86% [6/7] vs 50% [3/6] on RTX alone) and week 24 (86% [6/7] vs 67% [4/6]). Post-hoc analyses demonstrated rapid, dose-dependent responses: 1) CR/PR rates at week 5 were 57% (4/7) at 30 mg/kg HLX79+RTX vs 17% (1/6) with RTX alone; 2) median time to first CR/PR was ~3 weeks at 30 mg/kg vs ~11 weeks with RTX alone; 3) time-weighted proteinuria area under the curve, a measure of disease burden, declined dose-dependently vs RTX alone. HLX79 was well tolerated with no HLX79-related Grade ≥3 events.

Conclusion

HLX79 30 mg/kg + RTX produced the fastest, most complete responses: over half of patients achieved CR/PR within 5 weeks. RTX-only patients gradually responded through week 24, suggesting HLX79 accelerates, broadens, and deepens response vs RTX alone, lowering proteinuria burden and potentially short- and long-term risks. These findings support advancement of this novel, first-in-class molecule.

Efficacy

Funding

• Commercial Support – This study was supported by Shanghai Henlius Biotech, Inc.