Table 2.
Summary of the studies evaluating molecules in clinical development.
| Treatment | Treatment duration | Number of patients | Virological outcome | Development stage and References |
|---|---|---|---|---|
| Pegylated IFN-lambda 120 or 180 µg qw sc |
48 weeks | 33 | At week 24 of treatment: 4/10 patients are HDV PCR-negative |
Phase 2 [148] |
| Myrcludex B 2 mg/Kg qd sc, 24 weeks followed by pegylated IFN-alpha monotherapy, 48 weeks | 72 weeks | 24 | Decline in HDV RNA at week 24 of treatment: 1.67 log10 decrease in HDV RNA |
Phase 2 [149] |
| Myrcludex B 2 mg/Kg qd sc + pegylated IFN 24 weeks followed by Pegylated IFN-alpha monotherapy, 24 weeks | 48 weeks | Decline in HDV RNA at week 24 of treatment: 2.59 log10 decrease in HDV RNA |
||
| Pegylated IFN-alpha monotherapy | 48 weeks | Decline in HDV RNA at week 24 of treatment: 2.17 log10 |
||
| Myrcludex B 2, 5 or 10 mg qd sc | 24 weeks | 120 | Decline in HDV RNA at week 24 of treatment: 2 mg: 1.75 log10 5 mg: 1.6 log10 10 mg: 2.7 log10 |
Phase 2b [150] |
| Tenofovir 245 mg qd po | 24 weeks | Decline in HDV RNA at week 24 of treatment: 0.18 log10 |
||
| Myrcludex B 2 or 5 mg qd sc + pegylated IFN-alpha sc | 48 weeks | 30 | Decline in HDV RNA at week 48 of treatment: 2 mg: 3.62 log10 5 mg: 4.48 log10 |
Phase 2 [151] |
| Myrcludex B 2 mg qd sc | 48 weeks | 15 | Decline in HDV RNA at week 48 of treatment: 2.84 log10 |
|
| Pegylated IFN-alpha sc | 48 weeks | 15 | Decline in HDV RNA at week 48 of treatment: 1.14 log10 |
|
| Lonafarnib 100 or 200 mg bid iv | 4 weeks | 14 | Decline in HDV RNA at day 28 of treatment: 100 mg: 0.73 log10 200 mg: 1.54 log10 |
Phase 2A [152] |
| Lonafarnib 200 mg bid po | 12 weeks | 3 | Variation in HDV RNA at week 12 of treatment: 0.03 log10 |
Phase 2 [153] |
| Lonafarnib 300 mg bid po | 12 weeks | 3 | Decrease in HDV RNA at week 12 of treatment: 1.78 log10 |
|
| Lonafarnib 100 mg tid po | 5 weeks | 3 | Decrease in HDV RNA at week 4 of treatment: 1.31 log10 |
|
| Lonafarnib 100 mg bid po + pegylated IFN-alpha) qw sc | 8 weeks | 3 | Decrease in HDV RNA at week 8 of treatment: 2.19 log10 |
|
| LNF 100 mg po bid + ritonavir 100 mg qd po | 8 weeks | 3 | Decrease in HDV RNA at week 8 of treatment: 2.97 log10 |
|
| Lonafarnib 50 mg bid po (increased at 4 week intervals to 75 mg and then 100 mg) + ritonavir 100 mg bid po | 24 weeks | 15 | Dose escalation possible in 10 patients At the end of treatment, mean HDV RNA decline was 1.58 ± 1.38 log10 IU/mL |
Phase 2 [154] |
| Lonafarnib 50, 75 or 100 mg qd + ritonavir 100 mg qd po | 12 or 24 weeks | 21 | Decrease in HDV RNA at week 12 of treatment: 50 mg: 1.6 log10 75 mg: 1.3 log10 100 mg: 0.83 log10 Decrease in HDV RNA up to 3.7 log10 at week 24 of treatment |
Phase 2 [155] |
| Lonafarnib 50 mg bid po + ritonavir 100 mg bid po or Lonafarnib 25 mg bid po + Ritonavir 100 mg bid po or Lonafarnib 50 mg bid po + ritonavir 100 mg bid po + pegylated IFN-alpha qw sc or Lonafarnib 25 mg bid + Ritonavir 100 mg bid + pegylated IFN-alpha qw sc or Lonafarnib 50 mg bid po + ritonavir 100 mg bid po + addition of pegylated IFN-alpha qw for weeks 12–24 |
24 weeks | 33 |
Decrease in HDV RNA at week 24 of treatment: 21 of 33 patients had a > 2 log10 decrease in HDV RNA |
Phase 2 [156] |
| REP 2139-Ca 500 mg qw iv 15 weeks followed by REP 2139-Ca qw + pegylated IFN-alpha 15 weeks followed by pegylated IFN-alpha 33 weeks | 63 weeks | 12 | - At week 30 of treatment: >5log decline in HDV RNA in 11 patients Undetectable HDV RNA in 10 patients - At the end of treatment: HBs seroconversion in 5 patients; Undetectable HDV RNA in 9 patients; −18 months after treatment: 4 patients HBsAg negative 7 patients maintain undetectable HDV RNA |
Phase 2 [157], [158] |
Abbreviations: bid, twice a day; iv, intravenous; po, per os; qw, weekly; qd, daily; sc, subcutaneous, tid, three times per day.