Methoxy polyethylene glycol-epoetin beta 360micrograms/0.6ml solution for injection pre-filled syringes

Anemia associated with chronic kidney disease (CKD) and cancer is conventionally managed with packed red blood cell (PRBC) transfusions or erythropoietin-stimulating agents (ESAs) like epoetin alfa; however, transfusions are limited by complications such as alloimmunization and infection risk, which has led to ESAs becoming the preferred standard of care. Additional therapy may include iron supplementation, which potentially causes complications such as iron overload and infection risks in respective patient populations. The introduction of recombinant human erythropoietin (rhEPO) in 1989 improved anemia management but also raised concerns about adverse cardiovascular outcomes in many studies. Current guidelines promote careful ESA use to balance benefits and risks, while alternatives like hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) show promise in reducing such adverse effects. This review explores ESA trends, challenges, and emerging therapies for anemia in CKD and cancer patients and their implications in clinical use. The literature search for this narrative review was conducted on PubMed in January 2025. The search was restricted to articles published between January 2020 and January 2025, focusing on randomized controlled trials (RCTs), narrative reviews, systematic reviews, and meta-analyses. The initial PubMed search yielded 454 articles, which were subsequently screened according to the inclusion and exclusion criteria, resulting in a final selection of 58 publications that satisfied the eligibility requirements. Overall, evidence from these studies suggests that ESAs are considerably beneficial in correcting anemia and lowering the need for blood transfusions in adult patients with CKD. However, concerns about adverse cardiovascular outcomes and their effects on optimal hemoglobin targets have indicated the need to shift treatment approaches. These articles have also suggested recent developments, including the advent of HIF-PHIs and sodium-glucose cotransporter-2 (SGLT-2) inhibitors, which have been shown to offer safer and therapeutically promising alternatives in anemia of CKD and cancer-related anemia. Tailored approaches that take patient-specific factors into account are necessary for optimizing outcomes, suggesting that further research is required to evaluate the efficacy and risks of these novel treatments within clinical settings. The narrative review has summarized the benefits and drawbacks of ESAs as a widely used treatment for anemia of CKD and cancer-related anemia. Studies identified in this review have shown that ESAs are linked to increased risks of adverse cardiovascular events, tumor progression in cancers, and higher mortality rates. The emerging alternative of HIF-PHIs shows promise in mitigating these adverse risks with a similar treatment efficacy to ESAs. However, there is still a lack of long-term safety data on these treatment options, and future research should focus on determining this risk profile as well as potential dosing strategies to potentially guide the use of HIF-PHIs in future clinical practice as a novel therapeutic alternative for anemia of CKD and cancer-related anemia.

Abstract licence: CC BY

The covalent attachment of polyethylene glycol (PEG) to therapeutic agents, termed PEGylation, is a well-established and clinically proven drug delivery approach to improve the pharmacokinetics and pharmacodynamics of drugs. Specifically, PEGylation can improve the parent drug's solubility, extend its circulation time, and reduce its immunogenicity, with minimal undesirable properties. PEGylation technology has been applied to various therapeutic modalities including small molecules, aptamers, peptides, and proteins, leading to over 30 PEGylated drugs currently used in the clinic and many investigational PEGylated agents under clinical trials. Here, we summarize the diverse types of PEGylation strategies, the key advantages of PEGylated therapeutics over their parent drugs, and the broad applications and impacts of PEGylation in clinical settings. A particular focus has been given to the size, topology, and functionalities of PEG molecules utilized in clinically used PEGylated drugs, as well as those under clinical trials. An additional section has been dedicated to analyzing some representative PEGylated drugs that were discontinued at different stages of clinical studies. Finally, we critically discuss the current challenges faced in the development and clinical translation of PEGylated agents.

Abstract licence: CC BY

BackgroundAnemia is a common complication in patients with chronic kidney disease (CKD), for which recombinant human erythropoietin (rhEPO) is the standard treatment. UB-851 is a biosimilar rhEPO developed as an alternative to epoetin alfa (Eprex ® ). This study evaluated the clinical equivalence, safety, and immunogenicity of UB-851 compared with epoetin alfa in patients with anemia due to CKD receiving hemodialysis.MethodsIn this 52-week, multicenter, randomized, parallel-group, phase III trial, patients with anemic CKD undergoing maintenance hemodialysis were assigned to receive either UB-851 or epoetin alfa. Part I (weeks 1-24) included dose titration and hemoglobin (Hb) maintenance. Part II (weeks 25-52) focused on long-term safety and immunogenicity. The primary endpoint was the change in Hb levels from baseline to the efficacy evaluation period (weeks 21-24). The secondary endpoints included epoetin dose, adverse events (AEs), and anti-drug antibody formation.ResultsA total of 201 participants were randomized, and the mean change in Hb levels during the efficacy period was within the predefined equivalence margin (±0.6 g/dL) in both the intention-to-treat and per-protocol populations. Differences in weekly epoetin dose changes between the groups also fell within the predefined equivalence range (±45 IU/kg/wk). No significant differences were observed in the laboratory parameters, electrocardiograms, or vital signs. No anti-epoetin antibodies were detected in the UB-851 group. Regarding AEs, the UB-851 appears to be biosimilar to epoetin alfa.ConclusionUB-851 demonstrated clinical equivalence with epoetin alfa in maintaining Hb levels in patients with anemic CKD undergoing hemodialysis. The safety and immunogenicity profiles were comparable, supporting UB-851 as a biosimilar to epoetin alfa.

Abstract licence: CC BY-NC-ND