ATHENS, Greece—Amyndas Pharmaceuticals, a company focused on the development of novel complement therapeutics, has reported positive top-line Phase 2 results from its randomized, placebo-controlled clinical trial evaluating AMY-101 in 39 patients with periodontal inflammation and gingivitis.
AMY-101 is a novel complement C3-targeted therapeutic based on the 3rd-generation compstatin analog Cp40. Compstatins are synthetic cyclic peptides with strong affinity and selectivity for human and primate C3. Compstatins inhibit complement centrally, at the level of C3, and interrupt all downstream pathways of the complement activation cascade.
For the Phase 2 trial, AMY-101 was administered locally in the affected gingival tissues once a week for three weeks. The therapy demonstrated resolution of inflammation as measured by the reduction of bleeding (p < 0.001) and gingival inflammation index (p < 0.001). Inflammation resolution was demonstrated in a short time (21 days), and the benefit was maintained for at least 90 days without mechanical treatment. AMY-101 was also shown to be safe and well-tolerated in trial participants.
“We are excited with the robust signal for the efficacy of AMY-101 in these patients. This is not only a clear POC of AMY-101 in periodontal diseases, but also a potential paradigm shift in how these diseases can be treated. Current treatments for periodontal disease are limited to scaling and root planing, while patients with advanced periodontitis treatment may require surgical approaches,” stated Dr. Hatice Hasturk, director of the Forsyth Institute’s Center for Clinical and Translational Research, who conducted the AMY-101 trial. “The information gained from this study is very important, as it supports a potential new host-modulatory approach that can resolve periodontal inflammation, offering a more effective treatment of periodontal diseases.”
“We were impressed with the prominent therapeutic effect and long-lasting benefit of AMY-101 in the preclinical studies, and Amyndas proceeded to evaluate it in the clinic,” noted Dr. John Lambris, a leading complement researcher, the Dr. Ralph and Sallie Weaver Professor of Research Medicine at the University of Pennsylvania, inventor of AMY-101, and founder of Amyndas. “These top-line trial results now show that AMY-101 can indeed attenuate periodontal inflammation in patients and corroborate our hypothesis that it has the potential to become a new standard of care in periodontal treatment, potentially eliminating the need for recurrent invasive periodontal treatments.”
Gingivitis affects a large number of people, and if untreated can lead to periodontitis, which is a significant cause of tooth loss in adults. Approximately 743 million people — about 11.2 percent of the global population — are affected with a form of periodontitis.
The complement system has been shown to be involved in periodontal disease and inflammatory bone loss. Activation of the complement component C3 has been shown to fuel gum inflammation in preclinical studies in non-human primates. Local administration of AMY-101 was shown to reverse preexisting, naturally occurring periodontal inflammation in monkeys.
“We look forward to discussing these results with the FDA and other regulatory agencies to design the best path forward, ideally through a multi-center Phase 3 trial of AMY-101. There is a large proportion of the population that suffers from periodontal diseases and we hope to be able to provide a better treatment option,” added Dr. Despina Yancopoulou, managing director of Amyndas.
“If successful in Phase 3 clinical trials, AMY-101 has the potential to be the first local drug offering a novel mechanism of action for the treatment of periodontal diseases,” Hasturk concluded. “It is time to offer clinicians an effective alternative to combat periodontal disease.”