Alnylam B V — Onpattro EMA EPAR public assessment report (EMEA/H/C/004699, 2018)
Alnylam B V · 2018 · EMA EPAR public assessment report · company profile →
Report summary
The EMA granted marketing authorization for Onpattro (patisiran), an orphan medicinal product, for treating hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis). Patisiran, a first-in-class siRNA therapeutic, reduces TTR protein synthesis, improving polyneuropathy and cardiac manifestations. Accelerated assessment was granted due to unmet medical need. The pivotal APOLLO study demonstrated significant improvements in neurological impairment (mNIS+7), quality of life, and cardiac parameters compared to placebo over 18 months. Non-clinical studies confirmed TTR suppression and identified liver and spleen as target organs for toxicity. Safety concerns included infusion-related reactions and liver enzyme elevations, managed with premedication and monitoring. Vitamin A supplementation is recommended due to TTR reduction. Overall, Onpattro's benefits outweigh its risks for hATTR amyloidosis patients with stage 1 or 2 polyneuropathy.
Key findings — cited to the page
| Number of IRR symptoms (events) in patisiran-LNP group | 223 events | ALN-TTR02-004 Safety Population · p.138 |
| IRR in patisiran-LNP group (Study 004) | 18.9 % | Study 004 · p.138 |
| IRR in placebo group (Study 004) | 9.1 % | Study 004 · p.138 |
| Number of IRR symptoms (events) in placebo group | 105 events | ALN-TTR02-004 Safety Population · p.138 |
| Patients with at least 1 IRR and number of IRRs (AEs) in patisiran-LNP group | 18.9 % | ALN-TTR02-004 Safety Population · p.138 |
| Patients with at least 1 IRR and number of IRRs (AEs) in placebo group | 9.1 % | ALN-TTR02-004 Safety Population · p.138 |
| Infusion-related reaction (IRR) in patisiran-LNP group | 18.9 % | ALN-TTR02-004 Safety Population · p.134 |
| patients in Study 003 with at least 1 lymphocyte count <0.5 ×10^9/L (Grade 3) | 5 | Study 003 · p.163 |
| patients with platelet counts <50 x10^9/L (CTCAE Grade 3) | 0 | Study 004 · p.163 |
| hemoglobin value (Grade 3) in one patient at baseline | 79 g/L | Study 006 · p.163 |
| IRRs (placebo) | 9.1 % | Study 004 · p.184 |
| patients in Study 006 with at least 1 post-baseline lymphocyte count of <0.8 × 10^9/L (Grade 2) | 7 | Study 006 · p.163 |
Source: Alnylam B V ↗ · License: EMA - reuse permitted with acknowledgement. Summary and findings are extracted from the published document; every figure cites its page. Informational only — not investment advice. Explore the Neurology library →