Table 2.
siRNA therapeutics approved for clinical use
| Pathology/disease | Drug name | Delivery system | Mode of application | Target gene | Status/important past or ongoing studies | ClinicalTrials.gov identifier |
|---|---|---|---|---|---|---|
| Acute hepatic porphyria | Givosiran (Givlaari®) | GalNAc conjugate | s.c. | ALAS-1 | Approved (FDA: 2019, EU: 2020) | – |
| Real-world clinical management and safety | NCT04883905 | |||||
| Transthyretin-mediated amyloidosis | Patisiran (Onpattro®) | Lipid nanoparticle (DLin-MC3-DMA) | i.v. | TTR | Approved (FDA: 2018; EU: 2018) | – |
| Phase IV observational studies | NCT04561518, NCT04201418 (mutations) | |||||
| Pregnancy surveillance program | NCT05040373 | |||||
| Phase III, active, not recruiting | NCT03997383 | |||||
| Hypercholesterolemia | Inclisiran (Leqvio®) | GalNAc conjugate | s.c. | PCSK9 | Approved (EU: 2020; FDA: 2021) | – |
| Open-label extension | NCT03814187 | |||||
| Phase III, completed | ||||||
| Phase III, recruiting | NCT04765657 | |||||
| Retrospective multi-center analysis in Germany | NCT05438069 | |||||
| Homozygous familial hyper-cholesterolemia and elevated low-density lipoprotein cholesterol | Phase III, recruiting | NCT04659863 | ||||
| Phase III, recruiting | NCT04652726 | |||||
|
Hypercholesterolemia (Japanese participants with a high cardiovascular risk and elevated low-density lipoprotein cholesterol) |
Phase II, active, not recruiting | NCT04666298 | ||||
| Patients with cardiovascular disease and high cholesterol |
Phase II (ORION-3) Phase III (ORION-4) |
|||||
| Atherosclerotic cardiovascular disease | Phase III, recruiting | NCT05030428 | ||||
| Transthyretin-mediated amyloidosis | Vutrisiran (Amvuttra®) | GalNAc conjugate | s.c. | TTR | Approved (FDA: 2022) | – |
| Phase III, active, not recruiting | NCT03759379 (HELIOS-A) | |||||
| Phase III, active, not recruiting | NCT04153149 (HELIOS-B) | |||||
| Primary hyperoxaluria type 1 | Lumasiran (Oxluma®) | GalNAc conjugate | s.c. | GO | Approved (FDA: 2020; EU: 2020) | |
| Expanded access, approved for marketing | NCT04125472 | |||||
| Prospective observational study (BONAPH1DE) recruiting | NCT04982393 | |||||
| Phase III, active, not recruiting | NCT04152200 | |||||
| Primary hyperoxaluria type 1 (children and adults) | Phase III, completed | NCT03681184 | ||||
| Primary hyperoxaluria type 1 (infants and young children) | Phase III, active, not recruiting | NCT03905694 | ||||
| Phase II (long-term safety), active, not recruiting | NCT03350451 |
EU European Union, FDA US Food and Drug Administration, GalNAc N-acetylgalactosamine, i.v. intravenous, s.c. subcutaneous, siRNA small interfering RNA