Amyndas announces positive top-line Phase 2 results for investigational AMY-101 in adults with periodontal inflammation and gingivitis
- Study met primary endpoint and key secondary endpoints with statistically significant and clinically meaningful resolution of periodontal inflammation
- AMY-101 was safe and well-tolerated in trial recipients
- Plan for FDA end-of-phase 2 type B meeting and preparation for pivotal phase 3 study
March 9, 2021 – Amyndas Pharmaceuticals, a clinical-stage biopharmaceutical company focused on the development of novel complement therapeutics, announced today 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, administered locally in the affected gingival tissues once a week for three weeks, demonstrated resolution of inflammation as measured by the reduction of bleeding (p < 0.001) and gingival inflammation index (p < 0.001), the main determinants of this condition. Resolution of inflammation was demonstrated in a short time (21 days) and the benefit was maintained for at least 90 days, without mechanical treatment. Importantly, AMY-101 was also shown to be safe and well-tolerated in trial participants.
Hatice Hasturk, DDS, PhD, Director of Forsyth’s Center for Clinical and Translational Research, who conducted the AMY-101 trial, commented: “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 planning, while in patients with advanced periodontitis treatment may require surgical approaches. 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.”
Gingivitis (gum inflammation) affects a large number of people, and if it goes untreated and persists can lead to periodontitis, which is a significant cause of tooth loss in adults, and one of the most prevalent diseases worldwide, affecting around 50% of the population. Approximately 743 million people (about 11.2% of the global population) are affected with a form of periodontitis that can in turn raise the risk of other conditions, such as cardiovascular disease, diabetes, arthritis, and pregnancy complications.
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, leading to destruction of tooth-supporting bone, in preclinical studies in non-human primates. AMY-101 is a novel synthetic cyclic peptide designed to inhibit the complement cascade centrally at the level of C3 and local administration was shown to reverse pre-existing, naturally occurring periodontal inflammation in monkeys (https://pubmed.ncbi.nlm.nih.gov/26728318/). “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. 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” said Dr. John Lambris, the inventor of AMY-101 and founder of Amyndas, and a leading complement researcher and Dr. Ralph and Sallie Weaver Professor of Research Medicine at the University of Pennsylvania.
“We look forward to discussing these results with the U.S. 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” said Dr. Despina Yancopoulou, PhD, MBA, Amyndas’ Managing Director.
“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. It is the time to offer clinicians an effective alternative to combat periodontal disease” added Dr. Hatice Hasturk.
Editor’s Note: Dr. Lambris is an inventor of intellectual property licensed to Amyndas by the University of Pennsylvania and may be entitled to license consideration. Dr. Lambris is also a founder of Amyndas Pharmaceuticals, and both he and the University of Pennsylvania are equity holders of the company.
About Amyndas Pharmaceuticals
Amyndas Pharmaceuticals is a clinical-stage biopharmaceutical company committed to developing the most advanced complement therapies to treat inflammatory disorders, in areas of unmet medical need for which patients need better and safer therapies. Amyndas has a robust R&D complement program with the strongest and most diversified pipeline of C3 complement inhibitors in the field. For additional information please visit www.amyndas.com.
About the Forsyth Institute
Founded in 1910, the Forsyth Institute is the only independent research organization in the United States dedicated to understanding the important connections between oral health and overall wellness. Forsyth scientists are shaping the direction of personalized medicine through pioneering biomedical research and its direct application to new diagnostics, devices, and therapies. Forsyth combines its expertise in oral and associated systemic diseases with a relentless drive to ask — and answer — critical questions about how to best alleviate daily health challenges for billions. Forsyth is a not-for-profit organization that is also committed to treating underserved populations in local communities and on a national and global scale. To learn more about Forsyth, visit www.forsyth.org.
About the phase 2 trial
The phase 2 trial (Clinicaltrials.gov: NCT0394444) was a 3-month randomized, double-blind, split-mouth study in adults with gingivitis and chronic periodontal inflammation. The two halves of the mouth were randomized in each patient to receive AMY-101 or placebo (split-mouth design). AMY-101 or placebo was injected into the affected gingival tissues, once a week for three consecutive weeks. The study enrolled 39 subjects who were followed until day 90, for safety and efficacy assessments. The primary endpoint of change in the gingival index was evaluated at 21, 28, and 90 days after initial treatment, and AMY-101 demonstrated statistically significant improvement in all evaluations.
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, discovered at the University of Pennsylvania by Professor John Lambris and his team. Compstatins inhibit complement centrally, at the level of C3, and interrupt all downstream pathways of the complement activation cascade.
By inhibiting complement centrally, at the level of C3, AMY-101 and emerging 4th-generation compstatins, being developed by Amyndas, may prove more effective in treating a wide range of complement-mediated diseases than is possible with partial inhibitors of complement (such as anti-C5 agents) or other C3 inhibitors. Moreover, the novel characteristics of AMY-101 and 4th-generation compstatins (increased target affinity, improved PK profile and enhanced solubility) can broaden the spectrum of administration routes and allow for a reduced dosing frequency in chronic regimens in comparison with other C3 inhibitors.
AMY-101 has shown preliminary efficacy in various preclinical models ranging from periodontal disease, PNH, and C3G, to hemodialysis-induced inflammation, hemorrhagic shock and malaria-induced inflammation. With a target affinity in the sub-nanomolar range and an extended plasma half-life of more than 60 hours, AMY-101 is well suited for acute, and transient or prolonged therapeutic administration. New AMY-101 formulations for bi-weekly or weekly administration, are being developed for chronic applications, such as C3G and PNH.
AMY-101 is currently being evaluated in a phase 2 clinical trial in COVID-19 patients with ARDS, which has reached interim analysis. Amyndas is also advancing AMY-101 into phase 2 / 3 clinical trials in other complement-mediated conditions, while also developing a robust pipeline of next-generation candidates for further human clinical testing.
AMY-106 is a 4th-generation compstatin in preclinical development by Amyndas, with enhanced PK and solubility, which has shown an extended residence time in the vitreous of non-human primates of over 3 months and has the potential to significantly aid in the treatment of human complement-mediated retinal diseases. AMY-106 is designed for intravitreal administration and application in the treatment of age-related macular degeneration (AMD) and other ophthalmic conditions.
Despina Yancopoulou, PhD, MBA
Managing Director, Amyndas Pharmaceuticals