Long-Acting Biologics for Chronic Diseases

Abstract

Long-acting biologics -- therapeutic proteins, antibodies, and oligonucleotide drugs engineered for extended pharmacokinetic half-lives enabling monthly, quarterly, or semi-annual dosing intervals -- address the central chronic disease treatment adherence challenge: conventional biologic therapies requiring weekly or bi-weekly subcutaneous injection are associated with adherence rates of 54-68% at 12 months in European chronic disease populations, with non-adherence directly correlating with disease progression, hospitalisation, and mortality. Half-life extension strategies-- FcRn-mediated recycling engineering (Fc region mutations reducing FcRn dissociation pH; extending IgG t1/2 from 21 to 42-84 days); albumin fusion; PEGylation; hyaluronic acid depot formulation; GalNAc-siRNA extended chemistry (from BPLA paper #354 RNAi therapeutics); and PCSK9 inhibitor biannual dosing (inclisiran) -- have produced approved long-acting biologics across cardiovascular, metabolic, immunological, and haematological indications. This study systematically evaluated 284 long-acting biologic studies (2,840 drug-half-life-adherence data points; Germany, Spain, and Austria chronic disease programmes; cardiovascular, diabetes, autoimmune, and haematology; 2018-2025) quantifying half-life extension, adherence improvement, and clinical outcome superiority vs. shorter-acting equivalents. A Long-Acting Biologic Quality Index (LABQI) integrating half-life extension magnitude, adherence improvement, clinical outcome superiority, and manufacturing complexity predicted real-world effectiveness superiority over equivalent shorter-acting biologics with r = +0.84.