Efficacy and Safety of Pegmolesatide, a Novel Treatment for Anemia in Patients with Chronic Kidney Disease

Anemia is a common complication in patients with chronic kidney disease (CKD), significantly lowering patients’ quality of life and increasing cardiovascular risks. Traditionally, recombinant erythropoietin (EPO), such as epoetin alfa, has been used to treat anemia. However, frequent injections and immune reactions in some patients posed significant challenges. Recently, Pegmolesatide (HS-20039) has emerged as a promising alternative, addressing these limitations.

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What is Pegmolesatide?

Pegmolesatide (formerly known as Pegolsihematide or EPO-018B) is a novel EPO-mimetic peptide developed by China’s Hansoh Pharmaceutical Group. Traditional recombinant EPOs have structures similar or identical to human EPO, produced through genetic recombination technology. In contrast, Pegmolesatide is a structurally distinct synthetic peptide with PEGylation (attachment of polyethylene glycol) technology, significantly increasing its half-life and enabling longer-lasting effects.

Key Features and Advantages of Pegmolesatide

1. Extended Half-life and Reduced Injection Frequency: Unlike epoetin alfa, which typically requires several injections weekly, Pegmolesatide maintains efficacy with just a single subcutaneous injection every four weeks. With a half-life of approximately 140 hours, this significantly enhances patient convenience.
2. Reduced Immunogenicity: Being a synthetic peptide, Pegmolesatide has a lower risk of inducing immune reactions compared to conventional EPO medications. The PEGylation technology further enhances drug stability and minimizes immunogenicity.
3. Effective Anemia Management: A recent Phase 3 clinical trial in China confirmed Pegmolesatide’s non-inferiority compared to epoetin alfa in patients with nondialysis CKD. Pegmolesatide demonstrated an average hemoglobin (Hb) increase of 19.2 g/L, exceeding the efficacy of epoetin alfa (15.4 g/L).

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Clinical Trial Results Summary

The trial involved 173 patients with nondialysis CKD across 38 centers in China. Participants were randomly assigned, with 115 patients receiving Pegmolesatide injections every four weeks and 58 receiving epoetin alfa weekly or biweekly.

• Hemoglobin Level Improvement:
  • Pegmolesatide group: Mean increase of 19.2 g/L from baseline
  • Epoetin alfa group: Mean increase of 15.4 g/L
  • Pegmolesatide met the statistical criteria for non-inferiority.
• Maintenance of Target Hb Levels: Pegmolesatide showed more consistent maintenance of Hb levels within the target range (100-120 g/L), especially after anemia correction, compared to epoetin alfa.
• Adverse Events and Safety: The incidence of adverse events was comparable between the two groups. The most common adverse events were CKD progression and hypertension, with slightly higher hypertension rates in the Pegmolesatide group. No significant cardiovascular adverse events or fatal complications related to Pegmolesatide were observed.
• Immunogenicity: Antibody development occurred in 3.5% of patients receiving Pegmolesatide, with neutralizing antibodies identified in only one patient. This indicates lower immunogenicity compared to conventional EPO, suggesting promising long-term safety.

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Comparison Between Recombinant EPO and Pegmolesatide

Category	Pegmolesatide	Recombinant EPO (epoetin alfa)
Structure	Synthetic peptide	Recombinant protein similar to human EPO
Administration frequency	Every 4 weeks	1-2 times weekly
Half-life	Long (140 hours)	Short (8 hours)
Immunogenic risk	Low	Relatively high
Production method	Chemical synthesis (PEGylation)	Genetic recombination

Clinical Implications of Pegmolesatide

Pegmolesatide extends the dosing interval, greatly improving patient convenience while demonstrating comparable efficacy to traditional EPO treatments. Reducing injection frequency significantly enhances patient adherence and quality of life, marking a crucial advancement in anemia management.

Currently approved only in China, Pegmolesatide’s long-term safety and global clinical efficacy data are still accumulating. Nonetheless, its potential as a global treatment alternative remains highly promising.

Conclusion

Pegmolesatide offers a novel and practical solution for managing anemia in nondialysis CKD patients, effectively overcoming limitations associated with traditional ESA therapies. Future research and long-term safety data are eagerly anticipated.

Reference Xie J, et al. Randomized Trial of Pegmolesatide for the Treatment of Anemia in Patients With Nondialysis CKD. Kidney International Reports. 2025;10:720–729.