Table 3.
Effects of small-interfering RNA on hepatitis B surface antigen in clinical trials
| Agent | siRNA target | Carrier | Treatment regimen | Efficacy* |
|---|---|---|---|---|
| ARC-520 | 2 triggers targeting the X open reading frame | Cholesterol | 4 mg/kg; single dose [74] | 0.3 log IU/mL HBsAg reduction (NA treated HBeAg-negative patients); 1.4 log IU/mL HBsAg reduction (treatment naïve HBeAg-positive patients) |
| 2 mg/kg; Q1 month × 4 doses [82] | 0.54 log IU/mL HBsAg reduction (HBeAg positive patients); 0.38 log IU/mL HBsAg reduction (HBeAg negative patients) | |||
| 4 mg/kg; Q1 month for up to 9 doses [83],† | 2.6 log IU/mL HBsAg reduction in 2 patients and HBsAg seroclearance in 1 patient (HBeAg positive patients); 0.4 log IU/mL HBsAg reduction in 4 patients and HBsAg seroclearance in 1 patient (HBeAg negative patients) | |||
| ARB-1467 | 3 triggers targeting the S and X open reading frames | Lipid nanoparticles | 0.2 mg/kg; Q1 month × 3 doses [76] | 0.6 log IU/mL HBsAg reduction |
| 0.4 mg/kg; Q1 month × 3 doses [76] | 0.7 log IU/mL HBsAg reduction (HBeAg-positive patients); 0.9 log IU/mL HBsAg reduction (HBeAg-negative patients) | |||
| 0.4 mg/kg; Q2 weeks × 5 doses [84] | Maximum individual HBsAg reduction of 2.7 log IU/mL | |||
| AB-729 | 1 trigger targeting the X open reading frame | GalNAc | 60 mg; Q1 month × 6 doses; followed by Q3 months × 2 doses [86] | 1.89 log IU/mL HBsAg reduction |
| 60 mg; Q2 months × 6 doses [86] | 1.90 log IU/mL HBsAg reduction | |||
| 90 mg; Q2 months × 6 doses [86] | 2.16 log IU/mL HBsAg reduction | |||
| 90 mg; Q3 months × 4 doses [86] | 1.86 log IU/mL HBsAg reduction | |||
| RG-6346 | 1 trigger targeting the S open reading frame | GalNAc | 1.5 mg/kg; Q1 month × 4 doses [89] | 1.64 log IU/mL HBsAg reduction |
| 3.0 mg/kg; Q1 month × 4 doses [89] | 1.91 log IU/mL HBsAg reduction (NA treated patients); 1.02 log IU/mL HBsAg reduction (treatment naïve patients) | |||
| 6.0 mg/kg; Q1 month × 4 doses [89] | 1.87 log IU/mL HBsAg reduction | |||
| VIR-2218 | 1 trigger targeting the X open reading frame | GalNAc | 20 mg or 50 mg or 100 mg or 200 mg; Q1 month × 2 doses [75] | 70.8% of patients had more than 1.0 log IU/mL reduction in HBsAg. Among patients who achieved more than 1.0 log IU/mL, 70.6% of patients achieved HBsAg nadir of below 100 IU/mL |
| 200 mg; Q1 month × 6 doses [95] | 1.89 log IU/mL HBsAg reduction | |||
| 200 mg; Q1 month × 6 doses; combined with Q1 week pegylated interferon alpha-2a for 12 doses starting from week 12 [95] | 2.03 log IU/mL HBsAg reduction | |||
| 200 mg; Q1 month × 6 doses; combined with Q1 week pegylated interferon alpha-2a for 24 doses [95] | 2.55 log IU/mL HBsAg reduction | |||
| 200 mg; Q1 month × 6 doses; combined with Q1 week pegylated interferon alpha-2a for 48 doses [95] | 2.30 log IU/mL HBsAg reduction | |||
| JNJ-3989 | 2 triggers targeting the S and X open reading frames | GalNAc | 100 mg or 200 mg or 300 mg or 400 mg; Q1 month × 3 doses [77] | 1.93 log IU/mL HBsAg reduction |
| 40 mg; Q1 month × 12 doses [96] | 1.5 log IU/mL HBsAg reduction | |||
| 100 mg; Q1 month × 12 doses; combined with JNJ-6379 (capsid assembly modulator) [96] | 1.8 log IU/mL HBsAg reduction | |||
| 100 mg; Q1 month × 12 doses [96] | 2.1 log IU/mL HBsAg reduction | |||
| 200 mg; Q1 month × 12 doses [96] | 2.6 log IU/mL HBsAg reduction |
siRNA, small-interfering RNA; HBsAg, hepatitis B surface antigen; NA, nucleos(t)ide analogue; HBeAg, hepatitis B e-antigen; GalNAc, N-acetylgalactosamine.
*
HBsAg reductions depicted as mean log IU/mL unless otherwise specified.
†
Number of doses received varied from 4–9 doses, as the trial was terminated prior to completion.