Table 4.
Highlighted LNP-based nucleic acid therapeutics in the clinic. Drug products in clinical development or approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Company code names, generic (non-proprietary) names and company names for the products are given in brackets. Table adapted from Kulkarni et al. [18]
| Product | Nucleic acid / transgene | Indication | Administration route | Clinical stage | Ref. |
|---|---|---|---|---|---|
| Gene silencing | |||||
| Onpattro®, patisiran (Alnylam Pharmaceuticals) | siRNA-TTR | ATTRv amyloidosis | Intravenous | Approved (2018) | [223] |
| ALN-VSP02 (Alnylam/Ascletis) | siRNA-VSP/VEGF-A | Solid tumors (liver involvement) | Intravenous | Phase I (completed) NCT01158079 |
[224] |
| ARB-001467 (Arbutus Biopharma) | Three siRNAs against four HBV transcripts | Hepatitis B | Intravenous | Phase 2 (completed) NCT02631096 |
[225] |
| TKM-080301, TKM-PLK1 (Arbutus Biopharma) | siRNA-PLK1 | Solid tumors (NET, ACC) | Intravenous | Phase 1/2 (completed) NCT01262235 |
[226] |
| Atu027 (Silence Therapeutics) | siRNA-PKN3 (+gemcitabine) | Advanced / metastatic pancreatic cancer | Intravenous | Phase 1/2 (completed) NCT01808638 |
[227] |
| ND-L02-s0201, BMS-986263 (Nitto Denko Corporation / Bristol-Myers Squibb) | siRNA-HSP47 | Idiopathic pulmonary fibrosis | Intravenous | Phase 2 (recruiting) NCT03538301 |
[228] |
| EPHARNA (M.D. Anderson Cancer Center) | siRNA-EphA2 | Advanced or recurrent solid tumors | Intravenous | Phase 1 (recruiting) NCT01591356 |
[229] |
| Gene expression | |||||
| Lipo-MERIT (Biontech RNA Pharmaceuticals) | Four mRNAs encoding melanoma-associated antigens | Melanoma | Intravenous | Phase 1 (recruiting) NCT02410733 |
[230] |
| IVAC_W_bre1_uID and IVAC_M_uID (Biontech RNA Pharmaceuticals) | mRNAs encoding tumor-associated antigens and/or personalized neoantigens | Triple negative breast cancer | Phase 1 (recruiting) NCT02316457 |
||
| SGT-53 (SynerGene Therapeutics) | pDNA encoding wild-type p53 (+nab-paclitaxel / gemcitabine) | Metastatic pancreatic cancer | Intravenous | Phase 2 (recruiting) NCT02340117 |
[231] |
| MTL-CEBPA (Mina Alpha) | saRNA-CEBPα | Advanced liver cancer | Intravenous | Phase 1 (recruiting) NCT02716012 |
[232] |
| Gene editing | |||||
| NTLA-2001 (Intellia Therapeutics / Regeneron) | sgRNA-TTR mRNA-Cas9 |
ATTRv amyloidosis | Intravenous | Phase 1 planned |
[233] |