Clinical application of polysialylated therapeutic proteins.

While protein therapeutics are invaluable in managing numerous diseases, many require frequent injections to maintain therapeutically effective concentrations, due to their short half-life in circulation. PolyXen™, a platform technology employing biodegradable, non-immunogenic and hydrophilic polysialic acids (PSA) for drug delivery, is being utilized to overcome such limitations, thereby enabling the clinical utility of a broad range of protein therapeutics. Here, we report the recent progress on two development candidates, polysialylated erythropoietin (PSA-EPO) and polysialylated deoxyribonuclease I (PSA-DNase). Polysialylation led to a significantly prolonged circulating half-life (e.g., t1/2 of PSA-EPO = ~400 h in patients after subcutaneous administration, vs. t1/2 of EPO = ~22 h), improved stability against proteases and thermal stress, reduced clearance, and enhanced in vivo efficacy. This approach has been clinically validated in phase I and II studies of PSA-EPO for managing anemia in patients with chronic kidney disease (CKD).