Table 1.
Therapeutic oligonucleotides currently used in clinical trials of TTR amyloidosis.
| ISIS-TTRRx (ISIS Pharmaceuticals) | ALN-TTR02 (Alnylam Pharmaceuticals) | ALN-TTRSC (Alnylam Pharmaceuticals) | |
|---|---|---|---|
| mRNA target | 3′ UTR | 3′ UTR | 3′ UTR |
| Oligoncleotide | DNA | RNA | RNA |
| Nucleotide modification | PS, 2′-MOE | LNP | GalNAc |
| mRNA degradation | RNase H-dependent | RISC | RISC |
| Primary site of action | nucleus | cytoplasm | cytoplasm |
| Administration | subcutaneous | systemic infusion | subcutaneous |
| Premedication | No | Yes | No |
| Study start-estimated completion | 12/2012–11/2016 a | 11/2013–01/2017 b | 12/2014–12/2018 c |
| Dosing | weekly 300 mg (3 doses first week) | 0.3 mg/kg every 3 weeks | weekly 500 mg (5 doses first week) |
| Serum TTR knockdown | ~80% d | ~80% d | ~80% d |
| Disease | FAP, FAC, SSA | FAP | FAC |
a NCT01737398; b NCT01960348; c NCT02319005; d preliminary report.