Safety and Efficacy of the Complement Inhibitor AMY-101 in a Natural Model of Periodontitis in Non-human Primates

• Published in: Molecular therapy. Methods & clinical development Vol. 6; no. C; pp. 207 - 215
• Main Authors: Kajikawa, Tetsuhiro, Briones, Ruel A, Resuello, Ranillo R G, Tuplano, Joel V, Reis, Edimara S, Hajishengallis, Evlambia, Garcia, Cristina A G, Yancopoulou, Despina, Lambris, John D, Hajishengallis, George
• Format: Journal Article
• Language: English
• Published: United States Elsevier Limited 15.09.2017; American Society of Gene & Cell Therapy; Elsevier
• Subjects: AMY-101; Biofilms; Clinical trials; Cloning; complement; Complement component C3; Complement inhibitors; Complement system; compstatin; Drug dosages; Gum disease; Histology; Inflammation; Inflammatory diseases; Irritation; non-human primates; Original; Paroxysmal nocturnal hemoglobinuria; Periodontitis; Studies; compstatin; complement; inflammation; AMY-101; non-human primates; periodontitis
• ISSN: 2329-0501; 2329-0501
• DOI: 10.1016/j.omtm.2017.08.001

Periodontitis is a chronic inflammatory disease associated with overactivation of the complement system. Recent preclinical studies suggest that host-modulation therapies may contribute to effective treatment of human periodontitis, which may lead to loss of teeth and function if untreated. We previously showed that locally administered AMY-101 (Cp40), a peptidic inhibitor of the central complement component C3, can inhibit naturally occurring periodontitis in non-human primates (NHPs) when given once a week. This study was undertaken to determine the local safety of increasing doses of the drug as well as its efficacy when given at a reduced frequency or after systemic administration. Our findings have determined a local dose of AMY-101 (0.1 mg/site) that is free of local irritation and effective when given once every 3 weeks. Moreover, a daily subcutaneous dose of AMY-101 (4 mg/kg bodyweight) was protective against NHP periodontitis, suggesting that patients treated for systemic disorders (e.g., paroxysmal nocturnal hemoglobinuria) can additionally benefit in terms of improved periodontal condition. In summary, AMY-101 appears to be a promising candidate drug for the adjunctive treatment of human periodontitis, a notion that merits investigation in human clinical trials.