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Clinical Trial
. 2025 May;30(5):e70046.
doi: 10.1111/nep.70046.

Non-Inferiority of Subcutaneous Efepoetin Alfa Compared to Methoxy Polyethylene Glycol-Epoetin Beta in Stage 3 or 4 CKD Patients: Insights From a Phase 3 Trial

Simon D Roger  1 , Chew Ming Wong  2 , Phisitt Vejakama  3 , Kuspudji Dwitanto Rahardjo  4   5 , Bang-Gee Hsu  6 , Chang Meng Lee  7 , I-Wen Wu  8 , Chin-Chan Lee  8 , Tunggul Diapari Situmorang  9 , Pajaree Krisanapan  10 , Sadanah Aqashiah Mazlan  11 , Yu-Sen Peng  12 , Johanes Sarwono  13 , Norman De Asis  14 , Domingo Solimen  15 , Jonny  16 , Pornpen Sangthawan  17 , Jin-Bor Chen  18 , Chia-Liang Wang  19 , Sungjin Chung  20 , Agnes Jeans Villaflor  21 , Chul Woo Yang  22 , Wei-Chih Kan  23 , Yu Yang  24 , Jenny Rubio-Bicol  25 , Lee Yee Yan  26 , Sang Ho Lee  27 , Yi-Wen Chiu  28 , Cheng-Hsu Chen  29 , Ki Young Na  30 , Wan Hasnul Halimi Wan Hassah  31 , Young Sun Kang  32 , Bum-Soon Choi  33 , Grace Aquitania  34 , Ki Ryang Na  35 , Mai-Szu Wu  36 , Mohd Kamil Ahmad  37 , Rey Isidto  38 , Vincent Wu  39 , Goh Bak Leong  40 , Junne-Ming Sung  41 , Kajohnsak Noppakun  42 , Kang-Ju Chou  43 , Mohamad Zaimi Abdul Wahab  44 , Seok Joon Shin  45 , Pringgodigdo Nugroho  46
Affiliations
Clinical Trial

Non-Inferiority of Subcutaneous Efepoetin Alfa Compared to Methoxy Polyethylene Glycol-Epoetin Beta in Stage 3 or 4 CKD Patients: Insights From a Phase 3 Trial

Simon D Roger et al. Nephrology (Carlton). 2025 May.

Abstract

Aim: Efepoetin alfa, a novel long-acting erythropoietin (EPO)-hybrid Fc fusion protein, represents a promising erythropoiesis-stimulating agent (ESA) for addressing anaemia in chronic kidney disease (CKD) patients. This Phase 3 trial was to assess the efficacy and tolerability of subcutaneous efepoetin alfa in comparison to subcutaneous methoxy polyethylene glycol-epoetin beta in stage 3 or 4 CKD patients.

Methods: A randomised, multicentre, open-label Phase 3 trial enrolled 391 CKD stage 3 or stage 4 patients. Subjects underwent a 20-week correction period followed by an 8-week evaluation period. Responders continued treatment for an extra 24-week extension to evaluate long-term safety, maintenance effectiveness, and the longer treatment interval.

Results: In the efepoetin alfa Q2W (every 2 weeks) group, the response rate was 75.6%; while in the methoxy polyethylene glycol-epoetin beta Q2W group, the response rate was 69.3%. The difference in the response rate was 6.3% with 95% CI (confidence interval) -3.1% to 15.5%. The lower limit of the 95% CI was above the prespecified non-inferiority margin of -9.0%. Adverse event rates were comparable between the treatment groups.

Conclusion: Efepoetin alfa demonstrated non-inferiority to methoxy polyethylene glycol-epoetin beta in correcting anaemia and maintaining haemoglobin (Hb) levels among stage 3 and 4 CKD patients. Moreover, the safety profile of efepoetin alfa was comparable to methoxy polyethylene glycol-epoetin beta.

Keywords: anaemia; chronic kidney disease; efepoetin alfa; long‐acting erythropoiesis‐stimulating agent.

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Conflict of interest statement

Simon Roger has received speaker's fee and consultancy fees from Kalbe Genexine Biologics, and I‐Wen Wu has received consultancy from Innogene Kalbiotech Pte Ltd.

Figures

FIGURE 1
FIGURE 1
Study design. efepoetin alfa Q2W, twice‐monthly continuous efepoetin alfa; methoxy polyethylene glycol‐epoetin beta Q2W, twice‐monthly methoxy polyethylene glycol‐epoetin beta; efepoetin alfa Q4W, once‐monthly efepoetin alfa; methoxy polyethylene glycol‐epoetin beta Q4W, once‐monthly methoxy polyethylene glycol‐epoetin beta; R, randomization.
FIGURE 2
FIGURE 2
Patient disposition. Q2W, once every 2 weeks; Q4W, once every 4 weeks; ITT, intent‐to‐treat; mITT, modified intent‐to‐treat; EXT‐mITT, extension modified intent‐to‐treat; PP, per‐protocol; EXT‐PP, extension per‐protocol.
FIGURE 3
FIGURE 3
Mean haemoglobin (SD) values during correction and evaluation period (A) and extension period (B) with efepoetin alfa and methoxy polyethylene glycol‐epoetin beta. 2 W, once every 2 weeks; 4 W, once every 4 weeks; SD, standard deviation.
FIGURE 4
FIGURE 4
The percentage of the patients who had a Hb overshoot (Hb > 12 g/dL). Q2W, once every 2 weeks.
See this image and copyright information in PMC

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