AMY-101
Also known as: AMY‑101, AMY101, Compstatin analog 40, compstatin Cp40, Cp40
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Summary
AMY-101 (also called Cp40 or compstatin Cp40) is an investigational cyclic peptide that selectively blocks complement component C3. It is being studied as a host‑modulation therapy for complement‑driven inflammatory conditions, most notably periodontitis, and is under exploration for kidney injury and transplant‑related complications.
Mechanism of Action
AMY-101 binds with high affinity to the central complement protein C3, preventing its cleavage into C3a and C3b and thereby halting downstream activation of the alternative, lectin, and classical pathways. By stopping C3 activation, the peptide suppresses generation of the potent anaphylatoxin C3a, opsonization by C3b, and formation of the C5‑convertase, reducing inflammatory cell recruitment and tissue damage.
What the Research Shows
Pre‑clinical work in rodents and non‑human primates showed that AMY‑101 reduces complement‑driven inflammation and bone loss in models of periodontitis. A scoping review identified three animal studies and one Phase IIa trial indicating lowered clinical periodontal parameters after local or systemic administration. The Phase IIa study reported safety and reductions in gingival inflammation, probing depth, and bleeding without serious adverse events. Reviews of complement‑targeted therapies cite AMY‑101 among promising agents for kidney diseases, transplant rejection, and COVID‑19‑associated acute kidney injury, but clinical data beyond early‑phase periodontal studies remain limited.
Reported Benefits
Early human data suggest AMY‑101 can diminish gingival inflammation, bleeding, and pocket depth when used as an adjunct to conventional periodontal therapy. Animal models consistently show protection against inflammatory bone loss and suppression of pro‑inflammatory cytokines and matrix metalloproteinases. The peptide’s selective C3 inhibition offers a mechanistic advantage by targeting a central hub of complement activation, potentially extending benefit to other complement‑mediated disorders such as transplant‑related injury or COVID‑19‑associated kidney injury.
Limitations of the Evidence
Evidence is largely confined to pre‑clinical experiments and a single Phase IIa periodontal trial; larger, controlled studies are needed to confirm efficacy and durability. The therapeutic scope beyond oral disease remains speculative, with only mechanistic rationale and limited case‑series for kidney injury. No regulatory approval has been granted, and long‑term safety, optimal dosing, and comparative effectiveness versus existing complement inhibitors are still unknown.
Safety Considerations
The Phase IIa periodontal trial reported no serious adverse events and described AMY‑101 as well tolerated. However, overall safety data are limited to early‑phase and animal studies, so rare or delayed effects cannot be excluded. As a complement inhibitor, theoretical concerns such as impaired host defense against infections exist, but these have not been documented in the published abstracts.
How It Is Administered
AMY‑101 is a peptide administered by injection, typically intravenously or subcutaneously. Formulations described in the literature are experimental solutions for clinical or pre‑clinical use; no commercial product is currently available.
Routes of Administration
Goals & Uses
- Age‑related macular degenerationOphthalmologyModerate
- Treatment of C3 glomerulopathyNephrologyLow
- Complement inhibition in COVID-19 ARDSAnti Inflammatory / RespiratoryLow
- Solid organ transplantationTransplantLow
- Complement inhibition in periodontitisAnti InflammatoryModerate
- Paroxysmal nocturnal hemoglobinuria (PNH)HematologyLow
- Atypical hemolytic uremic syndrome (aHUS)Hematology / NephrologyLow
- Paroxysmal nocturnal hemoglobinuriaHematologyLow
- Severe COVID‑19Viral InfectionModerate
Contraindications
- Active encapsulated bacterial infection (e.g., Neisseria meningitidis)Infectious DiseaseHigh
- Known hypersensitivity to compstatin or its analoguesAllergyHigh
- Uncontrolled systemic infectionInfectious DiseaseHigh
- Known hypersensitivity to AMY‑101 or any excipientAllergyHigh
Adverse Effects
- Increased susceptibility to encapsulated bacterial infectionsImmunologicalUncommon
- Injection site reactionsLocalCommon
- HeadacheNeurologicCommonPain in the head or upper neck
- Infusion‑related reactionsGeneralCommon
- InfectionsImmunologicUncommon
- Infusion-related reactionsHypersensitivityUncommon
Drug Interactions
- Immunosuppressive agentsModerate
- Eculizumab / Ravulizumab (C5 inhibitors)Moderate
- Immunosuppressants (e.g., tacrolimus)Moderate
- Broad‑spectrum antibioticsModerate
Population Constraints
- PregnancyReproductive SafetyRelative
- Pediatric patientsAgeRelative
- Pregnant or lactating womenReproductiveRelative
- Patients with renal impairmentOrgan ImpairmentRelative
Regulatory Status
- European UnionInvestigationalClinical trial applications submitted; no marketing authorization.
- United StatesInvestigationalIND filed; Phase I/II trials ongoing.
- United KingdomInvestigationalUnder MHRA review for early‑phase studies.
Not approved in any jurisdiction; currently in Phase I/II clinical studies. Developed by Amylyx Pharmaceuticals (formerly by Apellis/Compstatin).
Evidence & Sources
- Journal ArticleModerateReddy YN, Siedlecki AM, Francis JM2017-01-01T00:00:00.000000Z
- Journal ArticleModerateAgnihotri R, Gaur S2022-01-01T00:00:00.000000Z
- Journal ArticleModerateKajikawa T, et al.2022-01-01T00:00:00.000000Z
- Journal ArticleModerateHajishengallis G, et al.2019-01-01T00:00:00.000000Z
- Journal ArticleModerateChen J, et al.2021-01-01T00:00:00.000000Z
- Journal ArticleModerateLi J, et al.2025-01-01T00:00:00.000000Z
Frequently Asked Questions
What condition has AMY‑101 been tested in humans?
A Phase IIa clinical trial evaluated AMY‑101 as an adjunct to non‑surgical periodontal therapy and reported reductions in gingival inflammation and bleeding without serious adverse events.
How does AMY‑101 differ from other complement inhibitors?
Unlike agents that block downstream components such as C5, AMY‑101 targets C3, the central hub of all complement pathways, potentially providing broader inhibition of complement‑mediated inflammation.
Is AMY‑101 approved for any medical use?
No. AMY‑101 remains investigational and is not approved by regulatory agencies for any indication.
What are the main safety concerns with AMY‑101?
Early trials have not identified serious safety signals, but limited data mean that rare adverse events, especially infection risk associated with complement blockade, have not been fully characterized.
Could AMY‑101 be useful for kidney disease?
Pre‑clinical and review articles suggest that C3 inhibition might mitigate complement‑driven kidney injury, including in COVID‑19, but clinical evidence is currently lacking.
What is AMY-101?
AMY-101 (also called Cp40 or compstatin Cp40) is an investigational cyclic peptide that selectively blocks complement component C3. It is being studied as a host‑modulation therapy for complement‑driven inflammatory conditions, most notably periodontitis, and is under exploration for kidney injury and transplant‑related complications.
What is AMY-101 used for?
AMY-101 is educationally associated with: Age‑related macular degeneration, Treatment of C3 glomerulopathy, Complement inhibition in COVID-19 ARDS, Solid organ transplantation, Complement inhibition in periodontitis, Paroxysmal nocturnal hemoglobinuria (PNH), Atypical hemolytic uremic syndrome (aHUS), Paroxysmal nocturnal hemoglobinuria, Severe COVID‑19. Educational only — not medical advice.
How is AMY-101 administered?
Recorded routes of administration: Intravenous, Subcutaneous.
What are the potential side effects of AMY-101?
Reported adverse effects include: Increased susceptibility to encapsulated bacterial infections, Injection site reactions, Headache, Infusion‑related reactions, Infections, Infusion-related reactions. This list is not exhaustive — consult a qualified clinician.
Who should avoid AMY-101?
Recorded contraindications: Active encapsulated bacterial infection (e.g., Neisseria meningitidis), Known hypersensitivity to compstatin or its analogues, Uncontrolled systemic infection, Known hypersensitivity to AMY‑101 or any excipient. Consult a qualified clinician before use.