This is the full length, pre-pro-protein structure as represented in NCBI Reference Sequence: NP_001726
. This peptide is cleaved into the complement C5 beta chain, complement C5 alpha chain and C5a anaphylatoxin (see the UniProt entry for the human protein P01031
C5 inhibition is a clinically validated mechanism that is utilised for the control and suppression of complement-induced hemolysis in patients with paroxysmal nocturnal hemoglobinuria (PNH). Eculizumab
is a clinically approved anti-C5 monoclonal antibody for PNH. Investigational Phase 1/2 anti-C5 monoclonal RG6101 (SKY59 [4
]; IMGT 783
) was granted FDA orphan drug designation
in September 2017 for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). Ra Pharmaceuticals is developing a C5 binding synthetic 15-amino-acid macrocyclic peptide (designated research code RA101495; Phase 2) for PNH and other complement-mediated illnesses. RA101495 was granted FDA orphan drug designation
for PNH in July 2017. RA101495 binds to a site on C5 distinct from the eculizumab
binding site, with the aim of overcoming eculizumab resistance, such as that observed in patients with the Arg885His C5 variant [5
] (note that RA101495 is also effective against this variant [4
]). It is also designed for subcutaneous self-administration, which would be more convenient for patients, who must be given eculizumab by i.v.
infusion by a healthcare professional.