Efpeglenatide, a Long-Acting Glucagon-Like Peptide-1 Receptor Agonist—Immunogenicity Profile Based on Preclinical and Clinical Studies

Once-weekly (QW), subcutaneous efpeglenatide (efpeg) is a long-acting glucagon-like peptide 1 receptor agonist, with glucose- and weight-lowering effects, in development for type 2 diabetes (T2D). Efpeg is based on a single amino acid-modified exendin analog coupled to a fragment crystallizable (Fc) fragment of the human immunoglobulin G molecule for slow clearance that permits QW dosing. As immunogenicity may hamper pharmacological effects, the incidence of anti-drug antibodies (ADAs) was assessed in efpeg studies. In a cynomolgus monkey study, no primate developed ADAs (Table). In clinical dose-finding studies (efpeg exposure in vitro neutralizing antibodies (nAbs) were detected. Primary and immunogenicity endpoints from efpeg QW clinical studies (u003e3 months) are shown (Table). In patients with T2D or obesity, efpeg QW led to significant reductions in glycated hemoglobin and body weight, respectively, with low immunogenicity ( Disclosure S. Del Prato: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, GlaxoSmithKline plc., Intarcia Therapeutics, Inc., Merck u0026 Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Servier, Sanofi, Takeda Pharmaceuticals U.S.A., Inc.. Research Support; Self; Merck u0026 Co., Inc., Novartis Pharmaceuticals Corporation, Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca. Speaker9s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Takeda Pharmaceuticals U.S.A., Inc.. Advisory Panel; Self; Janssen Biotech, Inc., Abbott. I. Choi: Employee; Self; Hanmi Pharmaceutical. Stock/Shareholder; Self; Hanmi Pharmaceutical. J. Kang: Employee; Self; Hanmi Pharmaceutical. M.E. Trautmann: Consultant; Self; ProSciento. Stock/Shareholder; Self; Eli Lilly and Company. Consultant; Self; Hanmi Pharmaceutical, CeQur Corporation, Intarcia Therapeutics, Inc., Servier. K. Yoon: None. C.H. Sorli: Employee; Self; Sanofi.