- |||||||||| AMY-101 / Amyndas
Review, Journal: C3 Targeted Complement Therapy for Chronic Periodontitis - A Scoping Review. (Pubmed Central) - Dec 20, 2022
Animal studies have shown that targeting complement C3 with its inhibitor like AMY-101 may help reduce inflammatory bone loss in CP...C3 targeted complement therapy may be regarded as a valuable adjunct to non-surgical periodontal treatment for CP. However, the results are still under investigation and require further verification through clinical trials.
- |||||||||| AMY-101 / Amyndas
Journal: Complement Is Required for Microbe-Driven Induction of Th17 and Periodontitis. (Pubmed Central) - Sep 30, 2022
A recent clinical trial showed that a complement C3 inhibitor (AMY-101) causes sustainable resolution of periodontal inflammation, the main effector of tissue destruction in this oral disease...Experiments in human gingival epithelial cells showed that C3a upregulated IL-6 production in cooperation with microbial stimuli that upregulated C3a receptor expression in ERK1/2- and JNK-dependent manner. In conclusion, complement links the periodontal microbiota challenge to Th17 cell accumulation and thus integrates complement- and Th17-driven immunopathology in periodontitis.
- |||||||||| AMY-101 / Amyndas
Journal: Insight into mode-of-action and structural determinants of the compstatin family of clinical complement inhibitors. (Pubmed Central) - Sep 29, 2022
Moreover, compstatin derivatives with enhanced pharmacodynamic and pharmacokinetic profiles are in clinical development (e.g., Cp40/AMY-101)...Functional studies provide further insight into physiological complement activation and corroborate the mechanism of its compstatin-mediated inhibition. Our study may thereby guide the application of existing and development of next-generation compstatin analogs.
- |||||||||| AMY-101 / Amyndas
Journal: Complement C3 inhibition in severe COVID-19 using compstatin AMY-101. (Pubmed Central) - Aug 22, 2022
Residual C3 activity in the three nonresponders suggested the presence of a convertase-independent C3 activation pathway overriding the drug's inhibitory activity. These findings support the design of larger trials exploring the potential of C3-based inhibition in COVID-19 or other complement-mediated diseases.
- |||||||||| Review, Journal: Complement System as a New Target for Hematopoietic Stem Cell Transplantation-Related Thrombotic Microangiopathy. (Pubmed Central) - Jul 29, 2022
Thus, it seems reasonable to propose complement inhibition therapy only to those patients exhibiting a clear complement activation according to the available biomarkers. Several agents are now available to inhibit complement activity: two drugs have been successfully used in TA-TMA, particularly in pediatric cases (eculizumab and narsoplimab) and others are at different stages of development (ravulizumab, coversin, pegcetacoplan, crovalimab, avacopan, iptacopan, danicopan, BCX9930, and AMY-101).
- |||||||||| AMY-101 / Amyndas
Review, Journal: C3-targeted host-modulation approaches to oral inflammatory conditions. (Pubmed Central) - Jun 14, 2022
AMY-101 has shown safety and efficacy in reducing gingival inflammation in a recent Phase 2a clinical study. We also discuss the potential of AMY-101 to treat peri-implant inflammatory conditions, where complement also seems to be involved and there is an urgent unmet need for effective treatment.
- |||||||||| AMY-101 / Amyndas
Clinical, P2a data, Journal: Phase 2a clinical trial of complement C3 inhibitor AMY-101 in adults with periodontal inflammation. (Pubmed Central) - Jan 11, 2022
P2a
In this conceptual review we discuss the activation, crosstalk and the therapeutic options that are available for regulation of the IIIS. AMY-101 causes significant and sustainable reduction in gingival inflammation without adverse events and merits further investigation for the treatment of periodontitis and other oral or peri-implant inflammatory conditions.
- |||||||||| Actemra IV (tocilizumab) / Roche, JW Pharma
Review, Journal: Inflammatory stress in SARS-COV-2 associated Acute Kidney Injury. (Pubmed Central) - May 21, 2021
It is highly possible that SARS-COV-2 infection may trigger the activation of multiple inflammatory pathways including angiotensin II, cytokine storm such as interleukin-6 (IL-6), C-reactive protein (CRP), TGF-β signaling, complement activation, and lung-kidney crosstalk to cause AKI. Thus, treatments by targeting these inflammatory molecules and pathways with a monoclonal antibody against IL-6 (Tocilizumab), C3 inhibitor AMY-101, anti-C5 antibody, anti-TGF-β OT-101, and the use of CRRT in critically ill patients may represent as novel and specific therapies for AKI in COVID-19 patients.
- |||||||||| AMY-101 / Amyndas
Trial completion, Enrollment change: A Study of the C3 Complement Inhibitor AMY-101 in Adults With Gingivitis (clinicaltrials.gov) - Feb 21, 2021
P2a, N=39, Completed,
Thus, treatments by targeting these inflammatory molecules and pathways with a monoclonal antibody against IL-6 (Tocilizumab), C3 inhibitor AMY-101, anti-C5 antibody, anti-TGF-β OT-101, and the use of CRRT in critically ill patients may represent as novel and specific therapies for AKI in COVID-19 patients. Recruiting --> Completed | N=30 --> 39
- |||||||||| AMY-101 / Amyndas
Trial completion date, Trial initiation date, Trial primary completion date: A Study of the C3 Inhibitor AMY-101 in Patients With ARDS Due to COVID-19 (SAVE) (clinicaltrials.gov) - Feb 21, 2021
P2, N=144, Not yet recruiting,
Recruiting --> Completed | N=30 --> 39 Trial completion date: Mar 2021 --> Dec 2022 | Initiation date: Jul 2020 --> Sep 2021 | Trial primary completion date: Jan 2021 --> Sep 2022
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Biomarker, Clinical, Journal: Complement C3 vs C5 inhibition in severe COVID-19: Early clinical findings reveal differential biological efficacy. (Pubmed Central) - Oct 30, 2020
These early clinical results offer important insights into the differential mechanistic basis and underlying biology of C3 and C5 inhibition in COVID-19 and point to a broader pathogenic involvement of C3-mediated pathways in thromboinflammation. They also support the evaluation of these complement-targeting agents as COVID-19 therapeutics in large prospective trials.
- |||||||||| AMY-101 / Amyndas
Review, Journal: Complement-Dependent Mechanisms and Interventions in Periodontal Disease. (Pubmed Central) - Sep 8, 2020
Specifically, interception of the complement cascade at its central component, C3, using a locally administered small peptidic compound (Cp40/AMY-101) protected non-human primates from induced or naturally occurring periodontitis. These studies indicate that C3-targeted intervention merits investigation as an adjunctive treatment of periodontal disease in humans.
- |||||||||| AMY-101 / Amyndas
Clinical, Journal: The first case of COVID-19 treated with the complement C3 inhibitor AMY-101. (Pubmed Central) - Jun 28, 2020
C3-targeted intervention may provide broader therapeutic control of complement-mediated inflammatory damage in COVID-19 patients. Herein, we report the clinical course of a patient with severe ARDS due to COVID-19 pneumonia who was safely and successfully treated with the compstatin-based complement C3 inhibitor AMY-101.
- |||||||||| AMY-101 / Amyndas
Enrollment open, Trial completion date, Trial primary completion date: A Study of the C3 Complement Inhibitor AMY-101 in Adults With Gingivitis (clinicaltrials.gov) - Jun 4, 2020
P2a, N=30, Recruiting,
Herein, we report the clinical course of a patient with severe ARDS due to COVID-19 pneumonia who was safely and successfully treated with the compstatin-based complement C3 inhibitor AMY-101. Not yet recruiting --> Recruiting | Trial completion date: Mar 2020 --> Dec 2020 | Trial primary completion date: Jan 2020 --> Sep 2020
- |||||||||| AMY-101 / Amyndas
Journal: Taming hemodialysis-induced inflammation: Are complement C3 inhibitors a viable option? (Pubmed Central) - Oct 29, 2019
Complement activation, early during the HD process, has been shown to fuel a multitude of detrimental thromboinflammatory reactions that collectively contribute to patient morbidity. Here we discuss emerging aspects of complement's involvement in HD-induced inflammation and put forth the concept that targeted intervention at the level of C3 might constitute a promising therapeutic approach in HD patients.
- |||||||||| AMY-101 / Amyndas
Clinical, Journal: Safety profile after prolonged C3 inhibition. (Pubmed Central) - Oct 8, 2019
In addition, a biodistribution study in a rhesus monkey indicated that the distribution of Cp40 in the body is associated with the presence of C3, concentrating in organs that accumulate blood and produce C3. Overall, our data suggest that systemic C3 inhibition in healthy adult non-human primates is not associated with a weakened immune system or susceptibility to infections.
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