Table 3.
RNA therapies in phase II or III clinical development.
| Treatment | Type | Amendment and Product Delivery | Mode of Delivery | Destination Site | Disease | Target Gene and Route | Phase and Identifier |
|---|---|---|---|---|---|---|---|
| RG-125 (AZD4076) | Anti-miR-103/107 | GalNAc-conjugated antagomiR | Subcutaneous | Liver | Type II diabetes, nonalcoholic fatty liver disease. | miR-103/107 | I/II NCT04120493 |
| Prexigebersen (BP1001-A) | ASO | Liposomal | Intravenous | Blood and/or immune cells | Acute myeloid leukemia, chronic myeloid leukemia | GRB2 mRNA | II NCT01159028; NCT04196257; NCT02781883 |
| WVE-120102 | ASO (allele-selective) | Stereopure ASO | Intrathecal | Brain | Huntington disease | U-variant of SNP rs362331 (SNP2) in HTT miRNA | I/II NCT03225846, NCT04617860 |
| siG12D-LODER | siRNA | Biodegradable polymeric matrix (PLGA) | Intratumoral | Tumor | Advanced pancreatic cancer | G12D-mutated KRAS miRNA | II NCT01188785; NCT01676259 |
| rAAV5-miHTT (AMT-130) | Pri-miR-451 backbone | Adeno-associated viral vector (AAV5) | Intrastriatal | Brain | Huntington disease | Huntingtin (HTT) miRNA | I/II NCT04120493 |
| Remlarsen (MRG-201) | miR-29 mimic. | Cholesterol-conjugated. | Intradermal | Skin | Keloid (pathological fibrosis) | miR-29 targetome | II NCT02603224, NCT03601052 |
| Miravirsen (SPC3649) | Anti-miR-122 | PS-β-d-oxy-LNA gapmer ODN | Subcutaneous | Liver | Hepatitis C virus infection | miR-122 | II NCT01646489, NCT01727934, NCT01872936, NCT01200420 |
| Olpasiran (AMG 890, ARO-LPA | siRNA | GalNAc-conjugated. | Subcutaneous | Liver | Cardiovascular disease | Apolipoprotein A (LPA) miRNA | II NCT03626662, NCT04270760 |
| Vupanorsen (AKCEA-ANGPTL3-LRx) | ASO | GalNAc-conjugated. | Subcutaneous | Liver | Dyslipidaemias, hyperlipidaemias, hyperlipoproteinaemias | Angiopoietin-like 3 (ANGPTL3) mRNA | II NCT04459767, NCT03371355, NCT04516291 |
| Danvatirsen (IONIS-STAT3-2.5Rx, AZD9150 | ASO | GalNAc-conjugated. | Intravenous | Tumor | Metastatic NSCLC, resectable early-stage NSCLC, pancreatic cancer, mismatch repair-deficient colorectal cancer | STAT3 miRNA | II NCT03819465, NCT03794544, NCT0298357 |
| Cemdisiran (ALN-CC5) | siRNA | GalNAc-conjugated. | Subcutaneous | Blood | Paroxysmal nocturnal hemoglobinuria, IgA nephropathy, Berger disease, glomerulonephritis | Complement 5 miRNA. | II NCT04601844, NCT02352493, NCT03841448, NCT03999840 |
| BMT 101 (cp-asiRNA) | Cell-penetrating asymmetrical siRNA | Carrier-free | Intradermal | Skin | Hypertrophic scar | Connective tissue growth factor (CTGF) miRNA | II NCT03133130, NCT04012099 |
| Apatorsen (OGX-427) | ASO | 2′-O-MOE-PTO gapmer | Intravenous | Tumor | Squamous cell lung cancer, non-squamous NSCLC, urological neoplasms, metastatic bladder cancer, urinary tract neoplasms, castration-resistant prostate cancer | HSP27 miRNA | II NCT01120470, NCT01454089, NCT01829113, NCT02423590 |
| Bamosiran (SYL040012) | siRNA | Carrier-free | Topical | Eye | Ocular hypertension, glaucoma | β-Adrenergic receptor 2 (ADRB2) miRNA | II NCT00990743, NCT01227291, NCT01739244, NCT02250612 |
| Donidalorsen (IONIS-PKK-LRx, ISIS 721744) | ASO | GalNAc-conjugated PS-2′-MOE ODN | Subcutaneous | Liver | Hereditary angioedema, COVID-19 | Prekallikrein (PKK) miRNA | II NCT03263507, NCT04030598, NCT04307381, NCT0454992 |
| Sepofarsen (QR-110) | ASO | Chemically modified. | Intravitreal | Eye | Leber congenital amaurosis type 10 (LCA10) is a hereditary or congenital eye disease that can cause blindness and vision and sensation disorders. It may also present with neurological manifestations. LCA10 falls under the category of eye diseases. | c.2991 + 1655A > G-mutated CEP290, pre-miRNA splicing | II/III NCT03140969, NCT03913143, NCT03913130 |
| Tominersen (RO7234292, HTT ASO, IONIS-HTTRx, ISIS-443139, ISIS-HTTRx, RG 6042) | ASO (allele-nonselective) | PS-2′-MOE gapmer | Intrathecal | Brain | Huntington disease | HTT miRNA | III NCT02519036, NCT04000594, NCT03342053, NCT03761849, NCT03842969 |
| AKCEA-TTR-LRx | ASO | GalNAc-conjugated. | Subcutaneous | Liver | Hereditary transthyretin-mediated amyloid polyneuropathy | Transthyretin (TTR) miRNA | III NCT04302064; NCT03728634; NCT04136184; NCT04136171 |
| Alicaforsen (ISIS 2302) | ASO | Phosphorothioate-modified. | Oral | Intestine | Crohn’s disease | ICAM1 miRNA | III NCT03473626, NCT00063830, NCT00063414, NCT00048113, NCT02525523 |
| Nedosiran (DCR-PHXC) | siRNA | GalNAc-conjugated. | Subcutaneous | Liver | Primary hyperoxaluria type 1 and type 2 are kidney and urological diseases characterized by excessive oxalate production. | Lactate dehydrogenase A enzyme (LDHA) miRNA. | III NCT03392896, NCT04555486, NCT04580420, NCT03847909, NCT04042402 |
| Tivanisiran (SYL1001) | siRNA | Carrier-free | Topical | Eye | Dry eye disease | TRPV1 is a member of the transient receptor potential cation channel subfamily V. | III NCT01438281, NCT01776658, NCT02455999, NCT03108664 |
| Pelacarsen (AKCEA-APO(a)-LRx, TQJ230) | siRNA | GalNAc-conjugated. | Subcutaneous | Liver | Hyperlipoproteinaemia | Apolipoprotein A miRNA | III NCT03070782, NCT03070782, NCT04023552 |
The table shows the phases of experimentation for miRNA-based therapies and their corresponding levels of study progression. This is indicated by an increase in the study phase. Abbreviations used in this text include the following: ASO, antisense oligonucleotide; GalNAc, N-acetylgalactosamine; LNA, locked nucleic acid; LODER, local drug eluter; NSCLC, non-small cell lung cancer; siRNA, small interfering RNA; SNP, single nucleotide polymorphism.