, Volume 78, Issue 15, pp 1625–1631 | Cite as

Patisiran: First Global Approval

  • Sheridan M. HoyEmail author
AdisInsight Report


Patisiran (ONPATTRO™) is a double-stranded small interfering RNA encapsulated in a lipid nanoparticle for delivery to hepatocytes. By specifically binding to a genetically conserved sequence in the 3′ untranslated region of mutant and wild-type transthyretin (TTR) messenger RNA, patisiran causes its degradation (via RNA interference) and subsequently a reduction in serum TTR protein levels and tissue TTR protein deposits. Patisiran has been developed by Alnylam Pharmaceuticals; it was recently approved in the USA for the treatment of the polyneuropathy of hereditary TTR-mediated amyloidosis (hATTR) in adults and subsequently approved in the EU for the treatment of hATTR in adults with stage 1 or 2 polyneuropathy. The recommended dosage, administered as a single intravenous infusion over approximately 80 min, is 0.3 mg/kg once every 3 weeks for patients weighing < 100 kg and 30 mg once every 3 weeks for patients weighing ≥ 100 kg. This article summarizes the milestones in the development of patisiran leading to these approvals.


Compliance with Ethical Standards


The preparation of this review was not supported by any external funding.

Conflict of interest

During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the author on the basis of scientific completeness and accuracy. Sheridan Hoy is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.


  1. 1.
    US National Library of Medicine. Genetics home reference: transthyretin amyloidosis. 2018. Accessed 16 Aug 2018.
  2. 2.
    Hawkins PN, Ando Y, Dispenzeri A, et al. Evolving landscape in the management of transthyretin amyloidosis. Ann Med. 2015;47(8):625–38.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    US FDA. FDA approves first-of-its kind targeted RNA-based therapy to treat a rare disease [media release]. 2018.
  4. 4.
    Alnylam Pharmaceuticals Inc. Onpattro (patisiran) lipid complex injection, for intravenous use: US prescribing information. 2018. Accessed 16 Aug 2018.
  5. 5.
    Alnylam Netherlands B.V. Onpattro 2 mg/mL concentrate for solution for infusion: EU summary of product characteristics. 2018. Accessed 5 Sept 2018.
  6. 6.
    Alnylam Pharmaceuticals Inc. Alnylam receives approval of ONPATTRO™ (patisiran) in Europe [media release]. 2018.
  7. 7.
    Alnylam Pharmaceuticals Inc. Alnylam Pharmaceuticals reports first quarter 2018 financial results and highlights recent period activity [media release]. 3 May 2018.
  8. 8.
    Coelho T, Adams D, Silva A, et al. Safety and efficacy of RNAi therapy for transthyretin amyloidosis. N Engl J Med. 2013;369(9):819–29.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Suhr OB, Coelho T, Buades J, et al. Efficacy and safety of patisiran for familial amyloidotic polyneuropathy: a phase II multi-dose study. Orphanet J Rare Dis. 2015;10:109.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Adams D, Coelho T, Conceicao I, et al. Phase 2 open-label extension (OLE) study of patisiran, an investigational RNA interference (RNAi) therapeutic for the treatment of hereditary ATTR amyloidosis with polyneuropathy [abstract no. PSY18 plus poster]. Value Health. 2017;20(5):A211–2.Google Scholar
  11. 11.
    Adams D, Gonzalez-Duarte A, O’Riordan WD, et al. Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis. N Engl J Med. 2018;379(1):11–21.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Goel V, Gosselin N, Jomphe C, et al. Population pharmacokinetic (PK)/pharmacodynamic (PD) model of serum transthyretin (TTR) following patisiran-LNP administration in healthy volunteers and patients with hereditary TTR-mediated (hATTR) amyloidosis with polyneuropathy [abstract no. EPR1139 plus presentation]. Eur J Neurol. 2018;25(Suppl. 2):354.Google Scholar
  13. 13.
    Polydefkis M, Ebenezer G, Adams D, et al. Effect of patisiran on nerve fiber density and amyloid content in skin: results from phase 2 open label extension (OLE) study in hATTR amyloidosis [abstract no. O3_3]. J Peripher Nerv Syst. 2017;22(3):360.Google Scholar
  14. 14.
    Zhang X, Goel V, Attarwala H, et al. Patisiran-LNP pharmacokinetics (PK), pharmacodynamics (PD), and exposure–response (E–R) relationship in patients with hereditary transthyretin-mediated (hATTR) amyloidosis with polyneuropathy [abstract no. EPR2142 plus presentation]. Eur J Neurol. 2018;25(Suppl. 2):460.Google Scholar
  15. 15.
    Solomon SD, Adams D, Kristen A, et al. Effects of patisiran, an RNA interference therapeutic, on cardiac parameters in patients with hereditary transthyretin-mediated amyloidosis: an analysis of the APOLLO study. Circulation. 2018.
  16. 16.
    Yamashita T, Sekijima Y, Koike H, et al. Patisiran, an investigational RNAi therapeutic for patients with hereditary transthyretin-mediated (hATTR) amyloidosis: phase 3 APOLLO study sub-analysis of Japanese patients [poster PC053]. In: XVIth International Symposium on Amyloidosis (ISA). 2018.Google Scholar
  17. 17.
    Suhr O, Gonzalez-Duarte A, O’Riordan W, et al. Long-term use of patisiran, an investigational RNAi therapeutic, in patients with hereditary transthyretin-mediated amyloidosis: baseline demographics and interim data from global open label extension study [poster]. In: XVIth International Symposium on Amyloidosis (ISA). 2018.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.SpringerAucklandNew Zealand

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