Phase 3 clinical trials with RNAi therapy siRNA and ASO in ATTRv-CM
| Study . | ENDEAVOUR . | APOLLO-B . | HELIOS B . | CARDIO-TTRANSFORM . |
|---|---|---|---|---|
| Main criteria of inclusion | ATTRv-CM, NYHA∗ < 4 PND†< 3, and TTR mutation Amyloid deposits MH of heart failure Involvement by echocardiogram | ATTRv-CM or ATTRwt-CM MH of heart failure | ATTRv-CM or ATTRwt-CM MH of heart failure | ATTRv-CM or ATTRwt-CM Interventricular septum thickness > 12 mm NYHA 1 to 3 |
| IMP | Revusiran | Patisiran | Vutrisiran | Eplontersen |
| Method of administration | SC | IV | SC | SC |
| Dose | 500 mg | 0.3 mg/kg | 25 mg | 45 mg |
| Rhythm of administration | 1 daily for 1 wk Then 1 every wk | Every 3 wk | Every 3 mo | Every month |
| N | 206 | 360 | 655 | 1400 |
| ATTRv, % | 100 | 20 | Unk | Unk |
| Variants | V122I, 57%; T60A, 16% | Unk | ||
| Age, y | 69 | 76 | Unk | Unk |
| NYHA3, stage, % | 31 | 8 | 0 (exclusion criteria) | Unk |
| Primary end points | CFB in 6-MWT to 18 mo; % reduction in serum TTR levels over 18 mo | CFB at mo 12 in 6-MWT | Composite end point of all-cause mortality and recurrent CV events | Composite outcome of CV mortality and recurrent CV clinical events up to wk 140 |
| End of trial | March 2017 | June 2022 | June 2024 | June 2025 |
| Results | Revusiran treatment was stopped after a median of 6.71 mo | Not yet | Not yet | |
| Primary end point | Not reached | Positive results on primary end point 6-MWT patisiran vs placebo: −8.15 mo vs −21.35 mo; P = .0162. At 12 mo∗ No effects on survival. | ||
| Safety | Mortality imbalance between treatment arms: 18 patients (12.9%) on revusiran and 2 (3.0%) on placebo during the on-treatment period | |||
| TTR knockdown | Mean > 80% reduction of serum TTR, mo 1 to 15 | Mean % reduction from baseline in serum TTR of 87% at mo 12 | ||
| Marketing authorization | No | No (not yet) | No | No |
| Study . | ENDEAVOUR . | APOLLO-B . | HELIOS B . | CARDIO-TTRANSFORM . |
|---|---|---|---|---|
| Main criteria of inclusion | ATTRv-CM, NYHA∗ < 4 PND†< 3, and TTR mutation Amyloid deposits MH of heart failure Involvement by echocardiogram | ATTRv-CM or ATTRwt-CM MH of heart failure | ATTRv-CM or ATTRwt-CM MH of heart failure | ATTRv-CM or ATTRwt-CM Interventricular septum thickness > 12 mm NYHA 1 to 3 |
| IMP | Revusiran | Patisiran | Vutrisiran | Eplontersen |
| Method of administration | SC | IV | SC | SC |
| Dose | 500 mg | 0.3 mg/kg | 25 mg | 45 mg |
| Rhythm of administration | 1 daily for 1 wk Then 1 every wk | Every 3 wk | Every 3 mo | Every month |
| N | 206 | 360 | 655 | 1400 |
| ATTRv, % | 100 | 20 | Unk | Unk |
| Variants | V122I, 57%; T60A, 16% | Unk | ||
| Age, y | 69 | 76 | Unk | Unk |
| NYHA3, stage, % | 31 | 8 | 0 (exclusion criteria) | Unk |
| Primary end points | CFB in 6-MWT to 18 mo; % reduction in serum TTR levels over 18 mo | CFB at mo 12 in 6-MWT | Composite end point of all-cause mortality and recurrent CV events | Composite outcome of CV mortality and recurrent CV clinical events up to wk 140 |
| End of trial | March 2017 | June 2022 | June 2024 | June 2025 |
| Results | Revusiran treatment was stopped after a median of 6.71 mo | Not yet | Not yet | |
| Primary end point | Not reached | Positive results on primary end point 6-MWT patisiran vs placebo: −8.15 mo vs −21.35 mo; P = .0162. At 12 mo∗ No effects on survival. | ||
| Safety | Mortality imbalance between treatment arms: 18 patients (12.9%) on revusiran and 2 (3.0%) on placebo during the on-treatment period | |||
| TTR knockdown | Mean > 80% reduction of serum TTR, mo 1 to 15 | Mean % reduction from baseline in serum TTR of 87% at mo 12 | ||
| Marketing authorization | No | No (not yet) | No | No |
6-MWT, 6-minute walk test, CFB, change from baseline; CV, cardiovascular; IMP, Investigational medicinal product; KCCQ, The Kansas City Cardiomyopathy Questionnaire; MH, medical history; NYHA, New York Heart Association; Unk, unknown.
Results have been presented but are not published yet.
CV hospitalizations and urgent heart failure visits.