Table 2.
Nucleic acid aptamers currently in the clinic
| Therapeutic purpose | Drug name and patent company | Target | Form and modification | Clinicaltrials.gov identifier (current status) | Condition being treated | Refs |
|---|---|---|---|---|---|---|
| Macular degeneration | Macugen® (Pegaptanib sodium) Pfizer/Eyetech |
Vascular Endothelial Growth factor isoform 165 (VEGF165) | 27-nt RNA 2′-fluoro pyrimidines, 2′-O-methyl purines, 3′-inverted dT, 40kDa PEGylated |
NCT00021736 (Phase II/III, completed); 233 NCT00040313 (Phase II, completed);234 NCT00056199 (Phase I, completed); 235 NCT00312351 (Phase 4, terminated); 236 NCT00321997 (Phase II/III, completed);237 NCT01487070 (Phase I, completed);238 Approved on Dec 2014 in the US and the EU for AMD treatment |
Age-related macular degeneration (AMD); Diabetic macular edema; Proliferative diabetic retinopathy |
14, 15, 154 |
| Zimura® (ARC1905) Ophthothech |
Complement component 5 (C5) | 38-nt RNA 2′-fluoro pyrimidines, 2′-O-methyl purines, 3′-inverted dT, 40kDa PEGylated |
NCT00709527 (Phase I, completed);239 NCT00950638 (Phase I, completed); 240 NCT02397954 (Phase II, completed);169 NCT02686658 (Phase II/III, recruiting);170 |
Age-related macular degeneration (AMD); Idiopathic Polypoidal Choroidal Vasculopathy (IPCV); Geographic Atrophy | 168 | |
| Fovista® (E10030) Opthothech/Retinal Consultants of Arizona |
Platelet-derived growth factor (PDGF) | 29-nt DNA 2′-O-methyl purines, 3′ inverted dT, 40 kDa PEGylated |
NCT00569140 (Phase I, completed);241 NCT01089517 (Phase II, completed);178 NCT02387957 (Phase II, recruiting);242 NCT02591914 (Phase I, ongoing);243 NCT01940887 (Phase III, recruiting);181 NCT01940900 (Phase III, ongoing);180 NCT01944839 (Phase III, recruiting);179 |
Age-related macular degeneration (AMD) | 174, 175 | |
| Coagulation | REG1 anticoagulation system (RB006 plus RB007) Regado Biosciences |
Coagulation factor IXa | 37-nt RNA The REG1 system consists of a drug (RB006, 37-nt RNA aptamer, 2′-ribo purine/2′-fluoro pyrimidine) and antidote (RB007, 17-nt, 40 KDa PEGylated, 2′-O-methyl antidote). |
NCT00113997 (Phase I, completed);244 NCT00715455 (Phase II, completed);189 NCT00932100 (Phase II, completed);188 NCT01872572 (Phase I, completed);190 NCT01848106 (Phase III, terminated, clinical hold due to serious anaphylactic reactions);191 |
Acute coronary syndrome (ACS); Cardiac catheterization (IV form); Coronary artery disease (CAD); Percutaneous coronary intervention (PCI) | 183–185, 187 |
| ARC1779 Archemix |
A1 domain of von Willebrand factor | 39-nt DNA 3′inverted dT, 2′-O-methyl with a single phosphorothioate linkage, 20 kDa PEGylated |
NCT00432770 (Phase I, completed);195 NCT00507338 (Phase II, terminated);198 NCT00632242 (Phase II, completed);245 NCT00694785 (Phase II, withdraw prior to enrollment);245 NCT00742612 (Phase II, terminated);197 |
Von Willebrand disease; Purpura; Thrombotic thrombocytopenic von Willebrand Disease Type-2b; Acute myocardial infarction; Percutaneous coronary intervention; Thrombosis |
192–194, 246 | |
| NU172 ARCA Biopharma |
Thrombin | 26-nt DNA Unmodified DNA |
NCT00808964 (Phase II, unknown, not verified recently);200 | Heart disease (e.g., used during cardiopulmonary bypass to maintain steady state of anticoagulation) | 199 | |
|
ARC19499 (BAX499) Baxalta US |
Tissue factor pathway inhibitor (TFPI) | 32-nt RNA 2′-O-methyl purine, 40 kDa PEGylated, 3′ inverted dT |
NCT01191372 (Phase I, terminated);203 | Hemophilia | 201, 202 | |
| Oncology | AS1411 (AGRO001) Antisoma |
Nucleolin | 26-nt DNA G-rich DNA, PEGlyated |
NCT00512083 (Phase II, completed);212 NCT00740441 (Phase II, unknown);213 NCT00881244 (Phase I, completed);211 NCT01034410 (Phase II, terminated);247 |
Acute myeloid leukemia (AML); Metastatic renal cell carcinoma; Advanced solid tumor; | 208–210 |
| NOX-A12 NOXXON Pharma |
Chemokine (C-X-C motif) ligand 12 (CXCL12) or Stromal cell-derived factor-1 (SDF-1) | 45-nt RNA (Spiegelmer®) L-Ribonucleic acid, PEGylated |
NCT00976378 (Phase I, completed);219 NCT01194934 (Phase I, completed);220 NCT01521533 (Phase II, completed);222 NCT01486797 (Phase II, ongoing, but not recruiting);221 |
Multiple myeloma (MM) and non-Hodgkin’s lymphoma (NHL); Chronic lymphocytic leukemia (CLL); Autologous stem cell transplantation; Hematopoietic stem cell transplantation; | 214, 215 | |
| Inflammation | NOX-E36 NOXXON Pharma |
Chemokine (C-C motif) ligand 2 (CCL2) | 40-nt RNA (Spiegelmer®) L-Ribonucleic acid, PEGylated |
NCT00976729 (Phase I, completed);248 NCT01085292 (Phase I/II, completed);226 NCT01372124 (Phase I, completed);249 NCT01547897 (Phase II, completed);227 |
Chronic inflammatory diseases; Type 2 diabetes mellitus; Systemic lupus erythematosus; albuminuria; Renal impairment |
74, 224, 225 |
| NOX-H94 NOXXON Pharma |
Hepcidin peptide hormone | 44-nt RNA (Spiegelmer®) L-Ribonucleic acid, PEGylated |
NCT01372137 (Phase I, completed);230 NCT01522794 (Phase I, completed);250 NCT01691040 (Phase II, completed); 231 NCT02079896 (Phase I/II, completed);232 |
Anemia; End stage renal disease; Anemia of chronic diseases; inflammation; | 228 |