Phase 3 clinical trials APOLLO A with patisiran and NEURO-TTR with inotersen for ATTRv-PN
| . | APOLLO-A . | NEURO-TTR . |
|---|---|---|
| Criteria of inclusion | NIS 5-130 TTR variant 18 to 85 y | NIS 10-130 TTR variant 18 to 82 y Amyloid deposit |
| Class | RNAi | ASO |
| IMP | Patisiran | Inotersen |
| Method of administration | IV∗ | SC |
| Dose | 0.3 mg/kg | 300 mg |
| Rhythm of administration | 1 per 3 wk | 1 per wk |
| Ratio of IMP-to-PB | 2:1 | 2:1 |
| N | 225 | 172 |
| Mean age, y | 59 | 59.2 |
| TTR variants, N | 39 | 27 |
| Val30Met TTR variants, % | 43 | 52 |
| Coutinho stage† 2 to 3 (%) | 54 | 43 |
| mNIS + 7 | 81 | 79.2 |
| Norfolk-QoL-DN | 55.5 | 48.4 |
| Primary end points | CFB of mNIS + 7 at 18 mo | CFB mNIS +7 and QOL-DN at week 66 |
| Secondary end points | CFB Norfolk QOL-DN, 10M-WT, R-ODS, and compass 31 mBMI | CFB Norfolk QOL-DN symptoms domain score, mBMI, and TTR |
| Exploratory end points | TTR, Echocardiography and measurement of NT-proBNP | |
| Results | ||
| Primary end points | ||
| LS mean changes | mNIS + 7 | mNIS + 7 |
| Placebo | +28 | +25.5 |
| IMP | −6.7 | +5.8 |
| % improvement/baseline | ||
| Placebo | 4% | 19% |
| IMP | 56% | 36% |
| Secondary end points | QOL-DN | QOL-DN (Iary end point) |
| Placebo | +19.8 | +12.7 |
| IMP | −6.7 | +1 |
| 10MWT m/s LS mean changes, PL/IMP | −0.24/+0.08 | NA |
| R-ODS LS mean changes, PL/IMP | −8.9/0.0 | NA |
| Compass31 LS mean changes, PL/IMP | +2.2/–5.3 | NA |
| mBMI LS mean changes, PL/IMP | −119/–3.7 | −0.8/–0.3 |
| Exploratory end points | ||
| Serum TTR median reduction level during the 18 mo | 81% | 74% (mean, nadir) |
| Time to reach study state, wk | 3 | 13 |
| Main AEs | Infusion-related reaction Peripheral edema | Thrombocytopenia Glomerulonephritis |
| Completed the intervention period (IMP) | 93% | 78% |
| MA | EMA-FDA | EMA-FDA |
| Coutinho stage 1 and 2 | Coutinho stage 1 and 2 |
| . | APOLLO-A . | NEURO-TTR . |
|---|---|---|
| Criteria of inclusion | NIS 5-130 TTR variant 18 to 85 y | NIS 10-130 TTR variant 18 to 82 y Amyloid deposit |
| Class | RNAi | ASO |
| IMP | Patisiran | Inotersen |
| Method of administration | IV∗ | SC |
| Dose | 0.3 mg/kg | 300 mg |
| Rhythm of administration | 1 per 3 wk | 1 per wk |
| Ratio of IMP-to-PB | 2:1 | 2:1 |
| N | 225 | 172 |
| Mean age, y | 59 | 59.2 |
| TTR variants, N | 39 | 27 |
| Val30Met TTR variants, % | 43 | 52 |
| Coutinho stage† 2 to 3 (%) | 54 | 43 |
| mNIS + 7 | 81 | 79.2 |
| Norfolk-QoL-DN | 55.5 | 48.4 |
| Primary end points | CFB of mNIS + 7 at 18 mo | CFB mNIS +7 and QOL-DN at week 66 |
| Secondary end points | CFB Norfolk QOL-DN, 10M-WT, R-ODS, and compass 31 mBMI | CFB Norfolk QOL-DN symptoms domain score, mBMI, and TTR |
| Exploratory end points | TTR, Echocardiography and measurement of NT-proBNP | |
| Results | ||
| Primary end points | ||
| LS mean changes | mNIS + 7 | mNIS + 7 |
| Placebo | +28 | +25.5 |
| IMP | −6.7 | +5.8 |
| % improvement/baseline | ||
| Placebo | 4% | 19% |
| IMP | 56% | 36% |
| Secondary end points | QOL-DN | QOL-DN (Iary end point) |
| Placebo | +19.8 | +12.7 |
| IMP | −6.7 | +1 |
| 10MWT m/s LS mean changes, PL/IMP | −0.24/+0.08 | NA |
| R-ODS LS mean changes, PL/IMP | −8.9/0.0 | NA |
| Compass31 LS mean changes, PL/IMP | +2.2/–5.3 | NA |
| mBMI LS mean changes, PL/IMP | −119/–3.7 | −0.8/–0.3 |
| Exploratory end points | ||
| Serum TTR median reduction level during the 18 mo | 81% | 74% (mean, nadir) |
| Time to reach study state, wk | 3 | 13 |
| Main AEs | Infusion-related reaction Peripheral edema | Thrombocytopenia Glomerulonephritis |
| Completed the intervention period (IMP) | 93% | 78% |
| MA | EMA-FDA | EMA-FDA |
| Coutinho stage 1 and 2 | Coutinho stage 1 and 2 |
AE, adverse event; CFB, change from baseline; EMA, European medicines agency; FDA, food and drug administration; IMP, investigational medicinal product; LS, least-squares; MA, marketing authorization; mBMI, modified body mass index; NIS, neuropathic impairment score; PB, placebo.
Greater or equal or a 0-point increase from baseline.
Coutinho stage 2 to 3, walking with aid or using a wheelchair.