Efepoetin Alfa Noninferior to Mircera When Correcting Anemia, Maintaining Hemoglobin in CKD

Key Takeaways

Efepoetin alfa showed noninferiority to methoxy polyethylene glycol-epoetin beta in anemia correction and hemoglobin maintenance in stage 3 and 4 CKD patients.
The phase 3 trial demonstrated comparable safety profiles between efepoetin alfa and Mircera, with a slightly higher response rate for efepoetin alfa.
The study emphasized the increasing prevalence of CKD and the necessity for effective treatment options.
Limitations included open-label design and dosage constraints, but the multicountry approach enhanced generalizability and external validity.

Patients with chronic kidney disease (CKD) receiving efepoetin alfa demonstrated a response rate of about 75.6%.

Efepoetin alfa (GX-E4; Genexine Biologics, KGbio) demonstrated noninferiority to methoxy polyethylene glycol-epoetin beta (Mircera; Roche) in correcting anemia and maintaining hemoglobin (Hb) levels in patients with stage 3 and 4 chronic kidney disease (CKD). The data, which were published in Nephrology, also highlighted comparable safety among the 2 treatments.¹

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About the Trial

Trial Name: A Study of Efepoetin Alfa in Treating Anaemia Associated With Chronic Kidney Diseases Patient

ClinicalTrials.gov ID: NCT04155125

Sponsor: PT Kalbe Genexine Biologics

Completion Date: June 30, 2023

CKD is a growing health issue, according to the study authors. The global prevalence is estimated to be about 11% to 13%, with 697.5 million cases of all-stage disease CKD and 1.2 million global deaths recorded in 2017. Additionally, they stressed that the incidence of CKD is projected to rise in the upcoming years because of an aging population and increased prevalence of comorbidities such as hypertension and type 2 diabetes.¹

Previously, in a phase 2 trial (NCT02044653)², the safety and efficacy of efepoetin alfa were found to be comparable to darbepoetin alfa in patients with CKD who were on hemodialysis and to those of Mircera in patients with CKD on peritoneal dialysis. To assess whether subcutaneous administration of efepoetin alfa is well-tolerated and effective, the investigators conducted a randomized, multicenter, open-label phase 3 clinical trial (NCT04155125)³ that enrolled 391 patients with stage 3 or 4 CKD. All patients were not undergoing dialysis, had presented with a baseline Hb level of 8 g/dL to less than 10 g/dL, and were either erythropoiesis-stimulating agent (ESA)–naïve or had ceased ESA treatment at least 3 months prior to screening.^1,3

Patients were randomly assigned to receive either efepoetin alfa (starting from 4 μg/kg body weight once per 2 weeks [Q2W], with subsequent titration based on Hb response; n = 193) or Mircera (0.6 μg/kg once per 2 weeks as starting dose; n = 197). All patients underwent a 20-week correction period for dosage titration and Hb correction, which was followed by an 8-week evaluation for efficacy assessments. Those who responded to efepoetin alfa—defined as the change from baseline in mean Hb during the evaluation period of at least 1 g/dL and the mean Hb of evaluation period falling within 10 to 12 g/dL without red blood cell transfusion—were eligible to continue treatment. Then, patients were randomly assigned again to continue receiving efepoetin alfa Q2W or increase to once per 4 weeks (Q4W) for an additional 24-week extension period to assess long-term safety and maintenance effects. Of note, patients who were assigned to the Q2W group received efepoetin alfa Q2W at the dose of response, whereas a dose equal to twice the Q2W dose was administered to those in the Q4W group.^1,3

The trial’s primary end point was the percentage of patients who achieved and maintained Hb response during the study’s evaluation period. Secondary end points included the mean change in Hb levels between baseline and evaluation periods as well as the mean change between evaluation and extension periods and the frequency of adverse events (AEs).^1,3

The findings indicate that noninferiority was confirmed, with a response rate of about 75.6% in the efepoetin alfa Q2W group compared with 69.3% in the Mircera Q2W group (difference: 6.3% [95% CI,−3.1, 15.5%]). Additionally, noninferiority of the mean changes in Hb levels between the baseline and evaluation periods were also confirmed, with a LS mean difference of –0.15 g/dL (95% CI, −0.33 to 0.02), and the lower limit of 95% CI was above the prespecified noninferiority margin of –0.75 g/dL. Further, the investigators noted that the comparison of efepoetin alfa Q2W versus Mircera Q4W and efepoetin alfa Q4W versus Mircera Q4W were performed separately. Noninferiority was confirmed in both comparisons because the lower limit of 95% CI was above the prespecified noninferiority margin of −0.75 g/dL.¹

Of note, patients treated with efepoetin alfa demonstrated a stable rise in Hb levels, with the percentage of those who had overshoot being lower than in the Mircera group. In subgroup analyses, there were no differences as a result of sex, age, and baseline Hb levels, according to the investigators.¹

Overall, the safety profile observed was considered comparable between the 2 treatment groups. A total of 44 serious AEs (SAEs) were reported in 30 patients (15.5%) in the efepoetin alfa QW group and 65 in 35 patients (17.8%) in the Mircera Q2W group. Additionally, SOCs with at least 2.5% of subjects having SAEs in either of the treatment groups were infections and infestations (efepoetin alfa Q2W: 7.8%; Mircera Q2W: 9.6%), renal and urinary disorders (efepoetin alfa Q2W: 1.6%; Mircera Q2W: 4.1%), cardiac disorders (efepoetin alfa Q2W: 3.6%; Mircera Q2W: 2.5%), and metabolism and nutrition disorders (efepoetin alfa Q2W: 2.1%; Mircera Q2W: 2.5%). The authors noted that further studies should be conducted to further understand the possible safety concerns.¹

“The limitations of this study were it being open-label, allowing potential assessment biases and the absence of blinded assessment of clinical endpoints. In addition, the choice of dosages for methoxy polyethylene glycol-epoetin beta was somewhat limited,” wrote the authors. “This study's strength lies in its multicountry and multisite design, which enhances the generalizability and external validity of its findings across diverse populations and healthcare systems…the study offers a comprehensive evaluation of both the efficacy and long-term safety of the novel treatment in a real-world clinical setting.”¹

REFERENCES

1. Roger SD, Wong CM, Vejakama P, et al. 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. Nephrology. 30:e70046. doi:10.1111/nep.70046

2. Study to Evaluate the Efficacy and Safety of GX-E2 in the Anemic Patients Diagnosed With Chronic Kidney Disease (CKD). ClinicalTrials.gov identifier: NCT02044653. Updated October 16, 2017. Accessed July 1, 2025. https://clinicaltrials.gov/study/NCT02044653

3. A Study of Efepoetin Alfa in Treating Anaemia Associated With Chronic Kidney Diseases Patient. ClinicalTrials.gov identifier: NCT04155125. Updated December 22, 2023. Accessed July 1, 2025. https://clinicaltrials.gov/study/NCT04155125

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