全球研發 | 創新聯合療法用於腎小球腎炎，HLX79聯合漢利康II期臨牀完成首例...

2025年8月6日，復宏漢霖（2696.HK）宣佈，潛在同類首創（first-in-class）人唾液酸酶融合蛋白HLX79（E-602）聯合漢利康（利妥昔單抗）治療活動期腎小球腎炎的II期臨牀試驗（HLX01HLX79-GN201）於中國完成首例患者給藥。漢利康現已在中國獲批用於治療非霍奇金淋巴瘤（NHL）、慢性淋巴細胞白血病（CLL）、類風濕性關節炎（RA），是目前國內唯一獲批用於自身免疫疾病治療的利妥昔單抗。此外，漢利康亦在拉美多國獲批用於治療血管炎肉芽腫（GPA）、顯微鏡下多血管炎（MPA）和尋常型天皰瘡（PV）等自身免疫疾病。

終末期腎病（ESRD）是慢性腎臟病（CKD）的終末階段，這一階段患者腎功能幾乎完全喪失，需長期依靠腎臟替代治療維持生命，具有疾病嚴重程度高、多併發症高發、治療花費負擔重等特點^[1]。中國ESRD患者數量位居全球首位，佔比接近30%，摺合現有患者人數達350萬^[2]。而中國終末期腎病的主要病因為腎小球腎炎，包括原發性腎小球腎炎和繼發性腎小球腎炎。原發性腎小球腎炎包括膜性腎病（MN）、局灶節段性腎小球硬化（FSGS）等。繼發性腎小球腎炎包括狼瘡腎炎（LN）、抗中性粒細胞胞質抗體（ANCA）相關性血管炎（AAV）腎損害等^[1]。

近年來，以利妥昔單抗（抗CD20單抗）等靶向抗體為代表的B細胞清除療法，已在全球多個市場獲批並被中華醫學會腎臟病學專家共識推薦用於治療腎小球腎炎^[1]。然而，許多患者對這類藥物的治療反應並不理想。糖免疫提供了一種治療自身免疫疾病的新方法。該策略通過酶解唾液酸糖苷，打破致病性免疫細胞的「保護屏障」， 從而增強其清除效果，幫助恢復機體免疫平衡。

HLX79是基於Palleon的EAGLE糖編輯平臺開發的潛在「同類首創」的人唾液酸酶融合蛋白。HLX79 通過酶解唾液酸糖苷，從而增強對兩類在自身免疫疾病中高度致病的免疫細胞的清除：一是驅動炎症的自身反應性記憶B細胞，二是促進纖維化和器官損傷的M2型巨噬細胞。

臨牀前研究表明，與利妥昔單抗單藥相比，HLX79與利妥昔單抗聯用的療效顯著提升，且不會引發CAR-T療法或T細胞結合劑相關的細胞因子釋放綜合徵（CRS）或免疫效應細胞相關神經毒性綜合徵（ICANS）。在此前的臨牀試驗中，HLX79展現出良好的安全性特徵，無劑量限制性毒性。HLX79聯用利妥昔單抗有望為活動期腎小球腎炎患者帶來臨牀獲益。

未來，復宏漢霖還將持續立足於未滿足的臨牀需求，充分發揮公司在抗體藥物領域的一體化平臺優勢，不斷拓展疾病領域和新分子類型，為全球患者帶來更多高質量、可負擔的創新治療方案。

參考文獻

[1] 中華醫學會腎臟病學分會專家組. 利妥昔單抗在腎小球腎炎中應用的專家共識[J]. 中華腎臟病雜誌, 2022, 38(2):151-160. [2] IQVIA《中國終末期腎病白皮書》

關於HLX01HLX79-GN201

本研究為一項雙盲、隨機對照、多中心的2期臨牀試驗，旨在評估HLX79聯合漢利康對比安慰劑在活動期腎小球腎炎（狼瘡腎炎（LN）和膜性腎病（MN））患者中的有效性、安全性和耐受性。研究分為兩個階段，第一階段為劑量遞增期，按照劑量遞增設計原則，合格的受試者將每周一次接受HLX79（10 mg/kg、20 mg/kg或30 mg/kg）聯合漢利康或漢利康安慰劑（375 mg/m2）給藥，主要研究目的為評價HLX79聯合漢利康對比安慰劑聯合漢利康治療活動期腎小球腎炎的安全性和耐受性；第二階段為初步療效探索期，篩選合格的受試者將按照2:2:1:1的比例，每周一次接受HLX79（高劑量/低劑量）聯合漢利康（375 mg/m2）、HLX79安慰劑聯合漢利康、或HLX79安慰劑聯合漢利康安慰劑給藥，主要研究目的為在標準治療基礎上，評價HLX79聯合漢利康、安慰劑聯合漢利康以及安慰劑治療活動期腎小球腎炎的臨牀療效，次要研究目的為評估其他臨牀療效、安全性、耐受性、藥代動力學（PK）特徵和免疫原性，探索性目的為評估潛在生物標誌物的動態變化。

關於復宏漢霖

復宏漢霖（2696.HK）是一家國際化的創新生物製藥公司，致力於為全球患者提供可負擔的高品質生物藥，產品覆蓋腫瘤、自身免疫疾病、眼科疾病等領域，已有6款產品在中國獲批上市，4款產品在國際獲批上市，5個上市申請分別獲中國藥監局、美國FDA和歐盟EMA受理。自2010年成立以來，復宏漢霖已建成一體化生物製藥平臺，高效及創新的自主核心能力貫穿研發、生產及商業運營全產業鏈。公司已建立完善高效的全球創新中心，按照國際藥品生產質量管理規範（GMP）標準進行生產和質量管控，不斷夯實一體化綜合生產平臺，其中，公司商業化生產基地已相繼獲得中國、歐盟和美國GMP認證。

復宏漢霖前瞻性佈局了一個多元化、高質量的產品管線，涵蓋約50個分子，並全面推進基於自有抗PD-1單抗H藥漢斯狀的腫瘤免疫聯合療法。截至目前，公司已獲批上市產品包括國內首個生物類似藥漢利康（利妥昔單抗）、自主研發的中美歐三地獲批單抗生物類似藥漢曲優（曲妥珠單抗，美國商品名：HERCESSI，歐洲商品名：Zercepac）、漢達遠（阿達木單抗）、漢貝泰（貝伐珠單抗）、全球首個獲批一線治療小細胞肺癌的抗PD-1單抗漢斯狀（斯魯利單抗，歐洲商品名：Hetronifly）以及漢奈佳（奈拉替尼）。公司亦同步就19個產品在全球範圍內開展30多項臨牀試驗，對外授權全面覆蓋歐美主流生物藥市場和眾多新興市場。

Henlius Doses First Patient in Phase 2 Trial of HLX79 and HANLIKANG for Glomerulonephritis

Shanghai, China, August 6, 2025 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first patient has been dosed in a phase 2 clinical trial (HLX01HLX79-GN201) for the potential first-in-class human sialidase enzyme therapeutic, HLX79 (E-602), in combination with Henlius’ self-developed HANLIKANG (rituximab) in patients with active glomerulonephritis.

End stage renal disease (ESRD), the last stage of chronic kidney disease (CKD), is characterised by near-total loss of kidney function, resulting in the need for renal replacement therapy. Patients face high disease severity, complications, and substantial economic burden due to the costs of treatment^[1]. China accounts for nearly 30% of global ESRD cases, with approximately 3.5 million patients^[2]. Glomerulonephritis can be classified into primary forms (e.g., membranous nephropathy [MN], focal segmental glomerulosclerosis [FSGS]) and secondary forms (e.g., lupus nephritis [LN], anti-neutrophilic cytoplasmic antibodies [ANCA]-associated vasculitis [AAV]), representing the leading cause of ESRD in China^[1].

HANLIKANG, approved in China for the treatment of non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, and rheumatoid arthritis, remains the only rituximab approved for an autoimmune indication in China. Depleting B cells with targeted antibodies such as rituximab (anti-CD20 mAb), has been approved in multiple markets for the treatment of glomerulonephritis. However, many patients have inadequate response to these drugs. Glyco-immunology provides a new approach to treating autoimmunity by degrading immune-inhibitory sialoglycan sugar molecules that help pathogenic immune cells evade immune clearance to enhance their depletion and restore immune balance.

HLX79 is a potential first-in-class human sialidase enzyme therapeutic developed based on Palleon’s EAGLE glycan editing platform and licensed in China by Henlius from Palleon. HLX79 degrades sialic acid, enhancing the clearance of two highly pathogenic immune cell populations in autoimmunity: autoreactive memory B cells, which drive inflammation, and M2-like macrophages, which promote fibrosis and organ damage. Preclinical studies of HLX79 in combination with rituximab demonstrate improved outcomes versus rituximab alone without the risk of cytokine release syndrome (CRS) or immune effector cell associated neurotoxicity syndrome (ICANS) associated with CAR T and T cell engagers. HLX79 has demonstrated a favourable safety profile with no dose-limiting toxicities in human clinical trials. It is expected that the combination of HANLIKANG and HLX79 will benefit patients with active glomerulonephritis.

Moving forward, Henlius will continue to focus on unmet clinical needs by fully leveraging its integrated platform advantages in antibody-based drugs, expanding disease areas, accelerating the development of differentiated molecules, and bringing more high-quality, affordable innovative therapies to patients worldwide.

About HLX01HLX79-GN201

This study is a double-blind, randomized, controlled, multicenter, Phase 2 study to evaluate the efficacy, safety, and tolerability of HLX79 in combination with HANLIKANG compared with placebo in patients with active glomerulonephritis (lupus nephritis (LN) and membranous nephropathy (MN)). The study includes two parts. Part 1 of the study is the dose escalation period. Eligible subjects will receive HLX79 (10 mg/kg, 20 mg/kg, or 30 mg/kg) or placebo combined with HANLIKANG (375 mg/m²) once a week. The primary objective is to evaluate the safety and tolerability of HLX79 in combination with HANLIKANG, and placebo in combination with HANLIKANG for glomerulonephritis. Part 2 of the study is the preliminary efficacy exploration period. Eligible subjects will receive HLX79 (high dose/low dose) combined with HANLIKANG (375 mg/m²), HLX79 placebo combined with HANLIKANG, or HLX79 placebo combined with HANLIKANG placebo once a  week at a ratio of 2:2:1:1. The primary objective of part 2 is to evaluate the clinical efficacy of HLX79 in combination with HANLIKANG, placebo in combination with HANLIKANG, as well as placebo alone, in subjects with glomerulonephritis on the basis of standard treatment. The secondary objectives include other clinical efficacy, safety, tolerability, pharmacokinetic (PK) characteristics, and immunogenicity. The exploratory objective is to evaluate the dynamic changes of potential biomarkers.

About Henlius

Henlius (2696.HK) is a global biopharmaceutical company with the vision to offer high-quality, affordable and innovative biologic medicines for patients worldwide with a focus on oncology, autoimmune diseases and ophthalmic diseases. Up to date, 6 products have been launched in China, 4 have been approved for marketing in overseas markets, and 5 marketing applications have been accepted for review in China, the U.S. and the EU, respectively. Since its inception in 2010, Henlius has built an integrated biopharmaceutical platform with core capabilities of high-efficiency and innovation embedded throughout the whole product life cycle including R&D, manufacturing and commercialization. It has established global innovation centre and Shanghai-based commercial manufacturing facilities certificated by China, the EU and U.S. GMP.

Henlius has pro-actively built a diversified and high-quality product pipeline covering about 50 molecules and has continued to explore immuno-oncology combination therapies with proprietary HANSIZHUANG (anti-PD-1 mAb) as the backbone. To date, the company's launched products include HANLIKANG (rituximab), the first China-developed biosimilar, HANQUYOU (trastuzumab, trade name: HERCESSI in the U.S., Zercepac in Europe), a China-developed mAb biosimilar approved in China, Europe and U.S., HANDAYUAN (adalimumab), HANBEITAI (bevacizumab), HANSIZHUANG (serplulimab, trade name: Hetronifly in Europe), the world’s first anti-PD-1 mAb for the first-line treatment of SCLC, and HANNAIJIA (neratinib). What’s more, Henlius has conducted over 30 clinical studies for 19 products, expanding its presence in major markets as well as emerging markets.

(復星醫藥)