Pegcetacoplan: A New Opportunity for Complement Inhibition in PNH

Weitz, Ilene C.

doi:10.2147/jbm.s362220

Cited by 8 publications

(2 citation statements)

References 27 publications

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“…Pegcetacoplan (SYFOVRE) is a complement inhibitor developed by Appelis Pharmaceuticals and is the first FDA approved medication for the treatment of GA in AMD [ 193 , 194 ]. It targets C3 and C3b in the complement system and may also regulate complement-mediated functions [ 195 , 196 ].…”

Section: Pegcetacoplan (Syfovre) For Geographic Atrophymentioning

confidence: 99%

The Complement System as a Therapeutic Target in Retinal Disease

Ong,

Zarnegar,

Selvam

et al. 2024

Medicina

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The complement cascade is a vital system in the human body’s defense against pathogens. During the natural aging process, it has been observed that this system is imperative for ensuring the integrity and homeostasis of the retina. While this system is critical for proper host defense and retinal integrity, it has also been found that dysregulation of this system may lead to certain retinal pathologies, including geographic atrophy and diabetic retinopathy. Targeting components of the complement system for retinal diseases has been an area of interest, and in vivo, ex vivo, and clinical trials have been conducted in this area. Following clinical trials, medications targeting the complement system for retinal disease have also become available. In this manuscript, we discuss the pathophysiology of complement dysfunction in the retina and specific pathologies. We then describe the results of cellular, animal, and clinical studies targeting the complement system for retinal diseases. We then provide an overview of complement inhibitors that have been approved by the Food and Drug Administration (FDA) for geographic atrophy. The complement system in retinal diseases continues to serve as an emerging therapeutic target, and further research in this field will provide additional insights into the mechanisms and considerations for treatment of retinal pathologies.

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Section: Pegcetacoplan (Syfovre) For Geographic Atrophymentioning

confidence: 99%

The Complement System as a Therapeutic Target in Retinal Disease

Ong,

Zarnegar,

Selvam

et al. 2024

Medicina

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“…Pegcetacoplan (APL-2/Empaveli) is a PEGylated cyclic peptide that functions as a complement C3 inhibitor. It received FDA approval in 2019 for the treatment of ocular diseases, including age-related macular degeneration (AMD) and paroxysmal nocturnal hemoglobinuria (PNH), based on successful clinical trials (Turecek et al, 2016;Hoy, 2021;Ji et al, 2021;Weitz, 2023). Other PEGylated TPPs, such as α1-antitrypsin, IFN α, and Fab fragments, have demonstrated increased residence time in the lungs and improved stability within the airways (Cantin et al, 2002;Koussoroplis et al, 2014;McLeod et al, 2015;Freches et al, 2017;Patil et al, 2018).…”

Section: Pegylated Antibodiesmentioning

confidence: 99%

Research progress on the PEGylation of therapeutic proteins and peptides (TPPs)

Li,

Tian

et al. 2024

Front. Pharmacol.

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With the rapid advancement of genetic and protein engineering, proteins and peptides have emerged as promising drug molecules for therapeutic applications. Consequently, there has been a growing interest in the field of chemical modification technology to address challenges associated with their clinical use, including rapid clearance from circulation, immunogenicity, physical and chemical instabilities (such as aggregation, adsorption, deamination, clipping, oxidation, etc.), and enzymatic degradation. Polyethylene glycol (PEG) modification offers an effective solution to these issues due to its favorable properties. This review presents recent progress in the development and application of PEGylated therapeutic proteins and peptides (TPPs). For this purpose, firstly, the physical and chemical properties as well as classification of PEG and its derivatives are described. Subsequently, a detailed summary is provided on the main sites of PEGylated TPPs and the factors that influence their PEGylation. Furthermore, notable instances of PEG-modified TPPs (including antimicrobial peptides (AMPs), interferon, asparaginase and antibodies) are highlighted. Finally, we propose the chemical modification of TPPs with PEG, followed by an analysis of the current development status and future prospects of PEGylated TPPs. This work provides a comprehensive literature review in this promising field while facilitating researchers in utilizing PEG polymers to modify TPPs for disease treatment.

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The complement system as a target in cancer immunotherapy

Merle,

Roumenina

2024

Eur J Immunol

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Malignant cells are part of a complex network within the tumor microenvironment, where their interaction with host cells and soluble mediators, including complement components, is pivotal. The complement system, known for its role in immune defense and homeostasis, exhibits a dual effect on cancer progression. This dichotomy arises from its antitumoral opsonophagocytosis and cytotoxicity versus its protumoral chronic inflammation mediated by the C5a/C5aR1 axis, influencing antitumor T‐cell responses. Recent studies have revealed distinct co‐expression patterns of complement genes in various cancer types, correlating with prognosis. Notably, some cancers exhibit co‐regulated overexpression of complement genes associated with poor prognosis, while others show favorable outcomes. However, significant intra‐patient heterogeneity further complicates this classification. Moreover, the involvement of locally produced and intracellular complement proteins adds complexity to the tumor microenvironment dynamics. This review highlights the unique interplay of complement components within different cancers and patient cohorts, showing that “one size does not fit all”, for complement in cancer. It summarizes the clinical trials for complement targeting in cancer, emphasizing the need for tailored therapeutic approaches. By elucidating the mechanistic basis of complement's context‐dependent role, this review aims to facilitate the development of personalized cancer therapies, ultimately improving patient care and outcomes.

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Pegcetacoplan: A New Opportunity for Complement Inhibition in PNH

Cited by 8 publications

References 27 publications

The Complement System as a Therapeutic Target in Retinal Disease

The Complement System as a Therapeutic Target in Retinal Disease

Research progress on the PEGylation of therapeutic proteins and peptides (TPPs)

The complement system as a target in cancer immunotherapy

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