{ "id": "ep03xc8qzg", "slug": "anivamersen", "title": "Anivamersen", "updated": "2026-10-20", "topic_path": [ { "id": "life", "label": "Life and health", "api_url": "https://www.edgepedia.org/api/v1/topics/life" }, { "id": "life.health", "label": "Human health and medicine", "api_url": "https://www.edgepedia.org/api/v1/topics/life.health" }, { "id": "life.health.medicines", "label": "Medicines and therapeutics", "api_url": "https://www.edgepedia.org/api/v1/topics/life.health.medicines" }, { "id": "life.health.medicines.cardiovascular-metabolic-and-endocrine-d", "label": "Cardiovascular, metabolic, and endocrine drugs", "api_url": "https://www.edgepedia.org/api/v1/topics/life.health.medicines.cardiovascular-metabolic-and-endocrine-d" }, { "id": "life.health.medicines.cardiovascular-metabolic-and-endocrine-d.cardiovascular-drugs", "label": "Cardiovascular drugs", "api_url": "https://www.edgepedia.org/api/v1/topics/life.health.medicines.cardiovascular-metabolic-and-endocrine-d.cardiovascular-drugs" }, { "id": "life.health.medicines.cardiovascular-metabolic-and-endocrine-d.cardiovascular-drugs.antiplatelet-and-antithrombotic-agents", "label": "Antiplatelet and antithrombotic agents", "api_url": "https://www.edgepedia.org/api/v1/topics/life.health.medicines.cardiovascular-metabolic-and-endocrine-d.cardiovascular-drugs.antiplatelet-and-antithrombotic-agents" } ], "geo": [ { "id": "geo.us.t1946.life.health.medicines.cardiovascular-metabolic-and-endocrine-d.cardiovascular-drugs", "label": "United States · 1946 to 2000: Cardiovascular drugs", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.us.t1946.life.health.medicines.cardiovascular-metabolic-and-endocrine-d.cardiovascular-drugs", "path": [ { "id": "geo.us", "label": "United States", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.us" }, { "id": "geo.us.t1946", "label": "United States · 1946 to 2000", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.us.t1946" }, { "id": "geo.us.t1946.life", "label": "Life and health", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.us.t1946.life" }, { "id": "geo.us.t1946.life.health", "label": "Human health and medicine", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.us.t1946.life.health" }, { "id": "geo.us.t1946.life.health.medicines", "label": "Medicines and therapeutics", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.us.t1946.life.health.medicines" }, { "id": "geo.us.t1946.life.health.medicines.cardiovascular-metabolic-and-endocrine-d", "label": "Cardiovascular, metabolic, and endocrine drugs", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.us.t1946.life.health.medicines.cardiovascular-metabolic-and-endocrine-d" }, { "id": "geo.us.t1946.life.health.medicines.cardiovascular-metabolic-and-endocrine-d.cardiovascular-drugs", "label": "Cardiovascular drugs", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.us.t1946.life.health.medicines.cardiovascular-metabolic-and-endocrine-d.cardiovascular-drugs" } ] } ], "excerpt": "Anivamersen (RB007, R01J) is an oligonucleotide antidote that reverses the factor IXa-inhibiting RNA aptamer pegnivacogin in the REG1 anticoagulation system; its phase 3 REGULATE-PCI trial was stopped early for allergic reactions.", "snippet": "Anivamersen (RB007, R01J) is an oligonucleotide antidote that reverses the factor IXa-inhibiting RNA aptamer pegnivacogin in the REG1 anticoagulation system; its phase 3 REGULATE-PCI trial was stopped early for allergic reactions.", "node": "life.health.medicines.cardiovascular-metabolic-and-endocrine-d.cardiovascular-drugs.antiplatelet-and-antithrombotic-agents", "markdown": "# Anivamersen\n\n**Anivamersen** (development codes RB007 and R01J) is an oligonucleotide reversal agent, or antidote, designed to inactivate the anticoagulant RNA aptamer [pegnivacogin](https://www.edgepedia.org/pegnivacogin) (RB006) in the REG1 anticoagulation system, an investigational therapy for patients undergoing percutaneous coronary intervention (PCI)[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC3895957/). It is a proposed International Nonproprietary Name, formulated as a solution for intravenous injection at a concentration of 48 mg/ml, and was developed by [Regado Biosciences](https://www.edgepedia.org/regado-biosciences), Inc.[2](https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-001384-23/EE)\n\n| Key fact | Detail |\n|---|---|\n| Identity | Oligonucleotide controlling agent for pegnivacogin; sponsor codes RB007 and R01J; proposed INN anivamersen[2](https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-001384-23/EE) • [1](https://pmc.ncbi.nlm.nih.gov/articles/PMC3895957/) |\n| Mechanism | Binds pegnivacogin through Watson-Crick base pairing, altering its conformation and releasing it from factor IX and factor IXa[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC3278067/) |\n| Speed of reversal | Anticoagulation reversed within 5 minutes of anivamersen at a 1:1 ratio; in a phase 2 study, aPTT returned to baseline within a median of 1 minute with no rebound through 7 days[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC6784064/) • [3](https://pmc.ncbi.nlm.nih.gov/articles/PMC3278067/) |\n| RADAR trial (phase 2b) | 640 non-ST-elevation ACS patients randomized to pegnivacogin with 25, 50, 75, or 100% anivamersen reversal or heparin; at least 50% reversal was required for safe sheath removal[5](https://pubmed.ncbi.nlm.nih.gov/22859796/) |\n| REGULATE-PCI (phase 3) | Planned 13,200 patients, stopped after 3,232 because of excess allergic reactions in the REG1 arm (10 serious allergic events vs 1 with bivalirudin)[6](https://pubmed.ncbi.nlm.nih.gov/26547100/) • [7](https://pmc.ncbi.nlm.nih.gov/articles/PMC4900189/) |\n| Phase 3 outcome | Primary ischemic endpoint odds ratio 1.05 (95% CI 0.80 to 1.39, P = 0.72); major or minor bleeding increased (OR 1.64, P = 0.002)[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC4900189/) |\n| Historical role | The first aptamer/antidote pair to enter clinical trials[8](https://pmc.ncbi.nlm.nih.gov/articles/PMC10647184/pdf/nihms-1932667.pdf) |\n\n## Mechanism of action\n\nPegnivacogin is a single-stranded RNA aptamer, attached to a 40 kDa polyethylene glycol carrier that reduces renal clearance and prolongs anticoagulant activity beyond 30 hours, that binds and inhibits activated coagulation factor IXa[9](https://www.sciencedirect.com/science/article/abs/pii/S0140673615005152) • [10](https://www.nature.com/articles/s41392-024-02112-8.pdf). Anivamersen is its complementary controlling agent: because aptamers are sequence-defined nucleic acids, a complementary oligonucleotide can bind through Watson-Crick base pairing, alter the aptamer's three-dimensional conformation, and inactivate it[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC3895957/). Anivamersen exerts its effect by binding pegnivacogin and releasing it from factor IX or factor IXa[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC3278067/).\n\nA distinctive property of this design is titratability. The degree of reversal is directly related to the molar ratio of the two components, so anivamersen-mediated reversal can be adjusted to the patient's clinical condition rather than being fixed by the drug's pharmacokinetics[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC3895957/).\n\n## Clinical development\n\n**Early studies.** In a phase 1 trial in 85 healthy volunteers, increasing intravenous bolus doses of pegnivacogin produced dose-dependent prolongation of the activated partial thromboplastin time and activated clotting time, which anivamersen rapidly restored to baseline[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC3278067/). In an early phase 2 study of 50 patients with stable coronary artery disease, anivamersen doses of 30 to 150 mg restored the aPTT to baseline within a median of 1 minute (25th and 75th percentiles, 1 and 2 minutes), with no rebound increase through 7 days[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC3278067/).\n\n**RADAR.** The RADAR trial was a randomized, partially blinded, multicenter, active-controlled, dose-ranging phase 2b study in 640 non-ST-elevation acute coronary syndrome patients managed with an early invasive strategy. Patients received pegnivacogin 1 mg/kg, which achieved more than 99% inhibition of factor IXa, followed by anivamersen doses designed to produce 25, 50, 75, or 100% reversal, or heparin[5](https://pubmed.ncbi.nlm.nih.gov/22859796/) • [11](https://pmc.ncbi.nlm.nih.gov/articles/PMC3739693/). The 25% reversal arm was stopped after 41 patients because of excess bleeding, and major bleeding fell in a dose-related fashion with higher reversal (20, 11, 8, and 7% in the 25, 50, 75, and 100% reversal arms versus 10% with heparin)[5](https://pubmed.ncbi.nlm.nih.gov/22859796/). The trial established that at least 50% reversal is required to allow safe femoral sheath removal after catheterization[5](https://pubmed.ncbi.nlm.nih.gov/22859796/).\n\n**REGULATE-PCI.** The phase 3 REGULATE-PCI trial (NCT01848106, EudraCT 2013-001384-23) compared REG1, given as pegnivacogin 1 mg/kg before PCI with anivamersen 0.5 mg/kg (about 80% reversal) afterward, against bivalirudin at 225 hospitals in North America and Europe[6](https://pubmed.ncbi.nlm.nih.gov/26547100/) • [12](https://www.acc.org/latest-in-cardiology/clinical-trials/2015/03/13/16/56/regulate-pci). The trial intended to enroll 13,200 patients but was curtailed after 3,232 because of an excess of allergic responses: 10 serious allergic events occurred within 24 hours of dosing in REG1-treated patients versus 1 with bivalirudin, and 9 of the 10 REG1 reactions occurred within minutes of dosing and before anivamersen administration, suggesting acute infusion reactions due to pegnivacogin[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC4900189/). The primary composite endpoint of death, myocardial infarction, or stroke was not reduced (odds ratio 1.05, 95% CI 0.80 to 1.39, P = 0.72), major bleeding was unchanged (OR 3.49, 95% CI 0.73 to 16.82, P = 0.10), and major or minor bleeding appeared increased (OR 1.64, 1.19 to 2.25, P = 0.002)[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC4900189/). The EU trial record lists the trial as prematurely ended, with a global end-of-trial date of 22 August 2014[13](https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-001384-23/results).\n\n## Significance\n\nPegnivacogin and anivamersen were the first aptamer/antidote pair to enter clinical trials, and efficacy and safety were seen in phase 1, 2a, and 2b studies[8](https://pmc.ncbi.nlm.nih.gov/articles/PMC10647184/pdf/nihms-1932667.pdf). The concept, intense intraprocedural anticoagulation that can be titrated back with a matched oligonucleotide antidote, addressed a long-standing trade-off in interventional cardiology between preventing ischemic events and limiting bleeding[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC3895957/). The phase 3 program did not confirm that benefit: the trial was stopped early for allergic reactions without evidence of offsetting benefit, and a later review notes that the mechanism responsible for those reactions had not been fully elucidated[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC4900189/) • [3](https://pmc.ncbi.nlm.nih.gov/articles/PMC3278067/). Because the trial was prematurely discontinued, it could not definitively answer whether reversible anticoagulation of this kind would fulfill its promise of greater efficacy without compromising safety[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC4900189/).\n\n## References\n\n1. [A Phase 2, randomized, partially blinded, active-controlled study assessing the efficacy and safety of variable anticoagulation reversal using the REG1 system in patients with acute coronary syndromes: results of the RADAR trial (PMC)](https://pmc.ncbi.nlm.nih.gov/articles/PMC3895957/)\n2. [EU Clinical Trials Register, EudraCT 2013-001384-23, trial record (EE)](https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-001384-23/EE)\n3. [New Antithrombotic Drugs: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: ACCP Evidence-Based Clinical Practice Guidelines (PMC)](https://pmc.ncbi.nlm.nih.gov/articles/PMC3278067/)\n4. [A Mini-Review: Clinical Development and Potential of Aptamers for Thrombotic Events Treatment and Monitoring (PMC)](https://pmc.ncbi.nlm.nih.gov/articles/PMC6784064/)\n5. [RADAR trial results (PubMed)](https://pubmed.ncbi.nlm.nih.gov/22859796/)\n6. [Effect of the REG1 anticoagulation system versus bivalirudin on outcomes after percutaneous coronary intervention (REGULATE-PCI): a randomised clinical trial (PubMed)](https://pubmed.ncbi.nlm.nih.gov/26547100/)\n7. [Translation and Clinical Development of Antithrombotic Aptamers (PMC)](https://pmc.ncbi.nlm.nih.gov/articles/PMC4900189/)\n8. [In vitro selection of aptamers and their applications (PMC)](https://pmc.ncbi.nlm.nih.gov/articles/PMC10647184/pdf/nihms-1932667.pdf)\n9. [Effect of the REG1 anticoagulation system versus bivalirudin on outcomes after percutaneous coronary intervention (REGULATE-PCI), The Lancet / ScienceDirect](https://www.sciencedirect.com/science/article/abs/pii/S0140673615005152)\n10. [Landscape of small nucleic acid therapeutics: moving from the bench to the clinic as next-generation medicines (Nature)](https://www.nature.com/articles/s41392-024-02112-8.pdf)\n11. [The REG1 anticoagulation system: a novel actively controlled factor IX inhibitor using RNA aptamer technology for treatment of acute coronary syndrome (PMC)](https://pmc.ncbi.nlm.nih.gov/articles/PMC3739693/)\n12. [REGULATE-PCI clinical trial summary, American College of Cardiology](https://www.acc.org/latest-in-cardiology/clinical-trials/2015/03/13/16/56/regulate-pci)\n13. [EU Clinical Trials Register, EudraCT 2013-001384-23, clinical trial results](https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-001384-23/results)\n\n---\n*Topic: Encyclopedia › Life and health › Human health and medicine › Medicines and therapeutics › Cardiovascular, metabolic, and endocrine drugs › Cardiovascular drugs › Antiplatelet and antithrombotic agents*\n\n*Initially written Oct 20, 2026*\n\n*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*\n\nLicense: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license\n", "same_as": [], "url": "https://www.edgepedia.org/anivamersen", "markdown_url": "https://www.edgepedia.org/anivamersen.md", "license": { "name": "Edgepedia Community License 1.0", "url": "https://www.edgepedia.org/edgepedia/license", "summary": "Free with credit, commercial use included. AI training is open to everyone. For other uses, organizations over USD 100M in revenue or 100M monthly users license separately.", "spdx": "LicenseRef-Edgepedia-Community-1.0" }, "credit": "\"Anivamersen\", Edgepedia (EdgeChat), https://www.edgepedia.org/anivamersen. Edgepedia Community License 1.0.", "credit_md": "\"[Anivamersen](https://www.edgepedia.org/anivamersen)\", Edgepedia (EdgeChat), [https://www.edgepedia.org/anivamersen](https://www.edgepedia.org/anivamersen). [Edgepedia Community License 1.0](https://www.edgepedia.org/edgepedia/license).", "credit_html": "\"Anivamersen\", Edgepedia (EdgeChat), https://www.edgepedia.org/anivamersen. Edgepedia Community License 1.0.", "speakable": "Anivamersen is an oligonucleotide antidote that reverses the factor IXa-inhibiting RNA aptamer pegnivacogin in the REG1 anticoagulation system; its phase 3 REGULATE-PCI trial was stopped early for allergic reactions." }