Alnylam Pharmaceuticals, Inc. — Amvuttra FDA Review (NDA215515, ORIG 1, 2022)
Alnylam Pharmaceuticals, Inc. · 2022 · FDA Review (openFDA) · company profile →
Report summary
This clinical review recommends approval for Alnylam Pharmaceuticals' Amvuttra (vutrisiran) for treating polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults. Amvuttra, an improved version of patisiran with less frequent dosing, demonstrated significant efficacy in the HELIOS-A study. Patients showed marked improvements in polyneuropathy scores (mNIS+7) and quality of life (Norfolk QoL-DN) compared to an external placebo group, alongside substantial TTR reduction. The drug's safety profile is acceptable, with common adverse events including arthralgia, dyspnea, and decreased vitamin A, which requires supplementation. No significant safety concerns were identified, and investigator financial disclosures did not impact study outcomes.
Key findings — cited to the page
| CTCAE category Grade 3 hematology abnormality (neutrophil count <1.0 x10^9/L) in vutrisiran group | 1 | Amvuttra (vutrisiran) · p.72 |
| Grade 3 abnormalities in chemistry parameters (low sodium related to renal failure) | 1 subject | HELIOS-A study · p.74 |
| Grade 3 abnormalities in chemistry parameters (low potassium related to furosemide use) | 1 subject | HELIOS-A study · p.74 |
| Grade 3 chronic kidney disease (eGFR <30 ml/min/1.73m2) | 1 subject | HELIOS-A study · p.74 |
| Applicant Proposed Indication | Treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults | Amvuttra (vutrisiran) · p.2 |
| Deaths in vutrisiran group (HELIOS-A study) | 3 | Amvuttra (vutrisiran) · p.61 |
| Received Date | April 14, 2021 | Amvuttra (vutrisiran) · p.2 |
| Death rate in patisiran active comparator group | 7 % | Patisiran · p.61 |
| Applicant Proposed Dosing Regimen | 25 mg administered by subcutaneous injection once every 3 months (quarterly) | Amvuttra (vutrisiran) · p.2 |
| Deaths in external placebo control group (APOLLO study) | 6 | APOLLO (Placebo) · p.61 |
| Death rate in external placebo control group (APOLLO study) | 8 % | APOLLO (Placebo) · p.61 |
| Deaths in patisiran active comparator group | 3 | Patisiran · p.61 |
Source: Alnylam Pharmaceuticals, Inc. ↗ · License: US Government public domain. Summary and findings are extracted from the published document; every figure cites its page. Informational only — not investment advice. Explore the Neurology library →