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- W2950958055 abstract "Therapeutic complement inhibition by eculizumab has revolutionized the treatment of paroxysmal nocturnal hemoglobinuria (PNH) with a major impact on its natural history. Nevertheless, emerging unmet clinical needs may benefit from the development of novel complement inhibitors. Novel strategies of complement inhibition exploit different agents targeting C5, as well as compound intercepting the complement cascade at the level of its key component C3, or even upstream at the level of component involved in complement alternative pathway initiation. Many of these agents are already in their clinical development; preliminary data together with a deep understanding of PNH biology may help to anticipate their possible clinical effect. Novel anti-C5 agents include monoclonal antibodies (even long-lasting) as well as other small molecules bioavailable by subcutaneous administration; an anti-C5 small interfering RNA has been developed too. All these anti-C5 agents seem to recapitulate safety and efficacy of current eculizumab treatment; their main improvement pertains to better patient compliance due to longer dosing interval and possible subcutaneous self-administration. The possibility of achieving a deeper C5 inhibition has been shown as well, but its actual clinical meaning remains to be elucidated. Upstream complement inhibitors include the anti-C3 small peptide compstatin (and its derivatives), and small inhibitors of complement factor D or complement factor B. This class of compound anticipates a possible efficacy in prevention of C3-mediated extravascular hemolysis, in addition to inhibition of intravascular hemolysis, possibly leading to improved hematological responses. The availability of all these compounds will result soon in a substantial improvement of PNH management." @default.
- W2950958055 created "2019-06-27" @default.
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- W2950958055 date "2017-12-07" @default.
- W2950958055 modified "2023-09-27" @default.
- W2950958055 title "Novel anti-complement agents for PNH:from eculizumab to complement inhibition 2.0" @default.
- W2950958055 hasPublicationYear "2017" @default.
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