Patisiran
{{Short description|Pharmaceutical drug}}
{{Use dmy dates|date=June 2022}}
{{Infobox drug
| drug_name =
| INN =
| type =
| image = Patisiran sodium.svg
| width = 375
| alt =
| caption =
| pronounce =
| tradename = Onpattro
| Drugs.com = {{drugs.com|monograph|patisiran-sodium}}
| MedlinePlus =
| DailyMedID = Patisiran
| pregnancy_AU = D
| pregnancy_AU_comment = {{cite web | title=Updates to the Prescribing Medicines in Pregnancy database | website=Therapeutic Goods Administration (TGA) | date=21 December 2022 | url=https://www.tga.gov.au/resources/resource/guidance/updates-prescribing-medicines-pregnancy-database | access-date=2 January 2023 | archive-date=3 April 2022 | archive-url=https://web.archive.org/web/20220403064059/https://www.tga.gov.au/updates-prescribing-medicines-pregnancy-database | url-status=live }}
| pregnancy_category=
| routes_of_administration = Intravenous
| class =
| ATCvet =
| ATC_prefix = N07
| ATC_suffix = XX12
| legal_AU = S4
| legal_AU_comment = {{cite web | title=Onpattro | website=Therapeutic Goods Administration (TGA) | date=2 December 2022 | url=https://www.tga.gov.au/resources/auspmd/onpattro | access-date=28 April 2023 | archive-date=5 February 2023 | archive-url=https://web.archive.org/web/20230205203513/https://www.tga.gov.au/resources/auspmd/onpattro | url-status=live }}{{cite web | title=Onpattro patisiran 10 mg/5 mL concentrated injection for infusion vial (380813) | website=Therapeutic Goods Administration (TGA) | date=22 November 2022 | url=https://www.tga.gov.au/resources/artg/380813 | access-date=28 April 2023 | archive-date=18 December 2022 | archive-url=https://web.archive.org/web/20221218000212/https://www.tga.gov.au/resources/artg/380813 | url-status=live }}{{cite web | title=Onpattro (Alnylam Australia Pty Ltd) | website=Therapeutic Goods Administration (TGA) | date=5 December 2022 | url=https://www.tga.gov.au/resources/prescription-medicines-registrations/onpattro-alnylam-australia-pty-ltd | access-date=28 April 2023 | archive-date=27 March 2023 | archive-url=https://web.archive.org/web/20230327062431/https://www.tga.gov.au/resources/prescription-medicines-registrations/onpattro-alnylam-australia-pty-ltd | url-status=live }}
| legal_BR =
| legal_BR_comment =
| legal_CA = Rx-only
| legal_CA_comment = {{cite web |url=https://pdf.hres.ca/dpd_pm/00060392.PDF |title=Onpattro PI |archive-url=https://web.archive.org/web/20220530063104/https://pdf.hres.ca/dpd_pm/00060392.PDF |archive-date=30 May 2022}}{{cite web | title=Summary Basis of Decision (SBD) for Onpattro | website=Health Canada | date=23 October 2014 | url=https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00446&lang=en | access-date=29 May 2022 | archive-date=31 May 2022 | archive-url=https://web.archive.org/web/20220531055109/https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00446&lang=en | url-status=live }}
| legal_DE =
| legal_DE_comment =
| legal_NZ =
| legal_NZ_comment =
| legal_UK =
| legal_UK_comment =
| legal_US = Rx-only
| legal_EU = Rx-only
| legal_EU_comment =
| legal_UN =
| legal_UN_comment =
| legal_status =
| bioavailability =
| protein_bound =
| metabolism =
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| index2_label = as salt
| CAS_number = 1420706-45-1
| CAS_supplemental =
| PubChem =
| IUPHAR_ligand =
| DrugBank = DB14582
| ChemSpiderID =
| UNII = 50FKX8CB2Y
| KEGG = D11116
| KEGG2 = D10794
| ChEBI =
| ChEMBL =
| NIAID_ChemDB =
| PDB_ligand =
| synonyms = ALN-18328
| IUPAC_name =
| C=412|H=520|N=148|O=290|P=40
| StdInChIKey = UBJHFPNBJDGZHL-UHFFFAOYSA-N
}}
Patisiran, sold under the brand name Onpattro, is a medication used for the treatment of polyneuropathy in people with hereditary transthyretin-mediated amyloidosis, a fatal rare disease that is estimated to affect 50,000 people worldwide.{{cite news|url=https://www.wsj.com/articles/fda-approves-first-drug-based-on-gene-silencing-research-1533923359|title=New Kind of Drug, Silencing Genes, Gets FDA Approval|vauthors=Loftus P|date=10 August 2018|work=The Wall Street Journal|access-date=10 August 2018|url-access=subscription|archive-date=10 August 2018|archive-url=https://web.archive.org/web/20180810192502/https://www.wsj.com/articles/fda-approves-first-drug-based-on-gene-silencing-research-1533923359|url-status=live}}{{cite journal | vauthors = Elafros MA, Kvalsund MP, Callaghan BC | title = The Global Burden of Polyneuropathy-In Need of an Accurate Assessment | journal = JAMA Neurology | volume = 79 | issue = 6 | pages = 537–538 | date = June 2022 | pmid = 35404377 | pmc = 9197927 | doi = 10.1001/jamaneurol.2022.0565 | s2cid = 248083689 }}
It is the first small interfering RNA-based drug approved by the U.S. Food and Drug Administration (FDA) and the first drug approved by the FDA to treat this condition. It is a gene silencing drug that interferes with the production of an abnormal form of transthyretin.{{cite journal | vauthors = Kristen AV, Ajroud-Driss S, Conceição I, Gorevic P, Kyriakides T, Obici L | title = Patisiran, an RNAi therapeutic for the treatment of hereditary transthyretin-mediated amyloidosis | journal = Neurodegenerative Disease Management | volume = 9 | issue = 1 | pages = 5–23 | date = February 2019 | pmid = 30480471 | doi = 10.2217/nmt-2018-0033 | doi-access = free }} Patisiran utilizes a novel approach to target and reduce production of the TTR protein in the liver via the RNAi pathway.{{Cite web|title=Onpattro (patisiran)|url=https://www.centerwatch.com/directories/1067-fda-approved-drugs/listing/3946-onpattro-patisiran|access-date=2021-06-18|website=www.centerwatch.com|archive-date=24 June 2021|archive-url=https://web.archive.org/web/20210624202025/https://www.centerwatch.com/directories/1067-fda-approved-drugs/listing/3946-onpattro-patisiran|url-status=live}}
Patisiran was developed and is marketed by Alnylam.{{cite web|url=https://www.bostonglobe.com/business/2012/10/22/alnylam-genzyme-form-alliance/hPpfyV15lwB2QlDJbSssBL/story.html|title=Alnylam, Genzyme Form Alliance|work=The Boston Globe| vauthors = Reidy C |date=22 October 2012|access-date=5 May 2021|archive-date=7 May 2021|archive-url=https://web.archive.org/web/20210507121804/https://www.bostonglobe.com/business/2012/10/22/alnylam-genzyme-form-alliance/hPpfyV15lwB2QlDJbSssBL/story.html|url-status=live}} The FDA considers it to be a first-in-class medication.{{cite report | title=New Drug Therapy Approvals 2018 | website=U.S. Food and Drug Administration (FDA) | date=January 2019 | url=https://www.fda.gov/media/120357/download | format=PDF | access-date=16 September 2020 | archive-date=17 September 2020 | archive-url=https://web.archive.org/web/20200917055627/https://www.fda.gov/media/120357/download | url-status=dead }}
History
Patisiran was granted orphan drug status, fast track designation, priority review and breakthrough therapy designation due to its novel mechanism and the rarity of the condition it treats.{{cite press release |title=FDA approves first-of-its kind targeted RNA-based therapy to treat a rare disease |url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm616518.htm |publisher=U.S. Food and Drug Administration (FDA) |date=10 August 2018 |access-date=11 August 2018 |archive-date=7 September 2018 |archive-url=https://web.archive.org/web/20180907185856/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm616518.htm |url-status=dead }}{{cite web|url=https://www.medscape.com/viewarticle/900541|title=FDA OKs Patisiran (Onpattro) for Polyneuropathy in hAATR|vauthors=Brooks M|date=10 August 2018|website=Medscape|publisher=WebMD|access-date=10 August 2018|archive-date=4 July 2019|archive-url=https://web.archive.org/web/20190704112331/https://www.medscape.com/viewarticle/900541|url-status=live}} It was approved for medical use in the United States and in the European Union in August 2018.{{cite web | title=Drug Approval Package: Onpattro (patisiran) | website=U.S. Food and Drug Administration (FDA) | date=7 September 2018 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210922Orig1s000TOC.cfm | access-date=2 September 2020 | archive-date=12 April 2021 | archive-url=https://web.archive.org/web/20210412015235/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210922Orig1s000TOC.cfm | url-status=dead }}{{cite web | title=Onpattro EPAR | website=European Medicines Agency (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/onpattro | access-date=2 September 2020 | archive-date=8 November 2020 | archive-url=https://web.archive.org/web/20201108104912/https://www.ema.europa.eu/en/medicines/human/EPAR/onpattro | url-status=live }} The per-patient cost is between {{US$|451430}} and {{US$|677145}} per year, depending on the number of vials needed.{{Cite book | title = Pharmacoeconomic Review Report: Patisiran (Onpattro) (Alnylam Netherlands B.V.): Indication: Treatment of polyneuropathy in adult patients with hereditary transthyretin-mediated amyloidosis [Internet] | chapter = Executive Summary | location = Ottawa (ON): Canadian Agency for Drugs and Technologies in Health | date = August 2019 | via = National Center for Biotechnology Information | url = https://www.ncbi.nlm.nih.gov/books/NBK549697/ | access-date = 3 April 2021 | archive-date = 20 October 2021 | archive-url = https://web.archive.org/web/20211020025209/https://www.ncbi.nlm.nih.gov/books/NBK549697/ | url-status = live }}
{{cite web|url=https://www.bloomberg.com/news/articles/2018-08-10/alnylam-wins-first-u-s-drug-approval-in-rare-genetic-disease|title=Rare-Disease Treatment From Alnylam to Cost $450,000 a Year|vauthors=Lipschultz B, Cortez M|date=10 August 2018|website=Bloomberg|access-date=11 August 2018|archive-date=14 November 2019|archive-url=https://web.archive.org/web/20191114184809/https://www.bloomberg.com/news/articles/2018-08-10/alnylam-wins-first-u-s-drug-approval-in-rare-genetic-disease|url-status=live}}{{Cite web|title=Onpattro Prices, Coupons & Patient Assistance Programs|url=https://www.drugs.com/price-guide/onpattro|access-date=2021-06-23|website=Drugs.com|archive-date=24 June 2021|archive-url=https://web.archive.org/web/20210624212046/https://www.drugs.com/price-guide/onpattro|url-status=live}}
Formulation
The siRNA active component of Patisiran is formulated into lipid nanoparticles, which protect the RNA and facilitate its delivery to target tissues. The lipid nanoparticle formulation includes buffer components, as well as the lipid components DLin-MC3-DMA, Distearoylphosphatidylcholine, cholesterol, and the PEGylated lipid DMG-PEG 2000.{{cite journal | vauthors = Akinc A, Maier MA, Manoharan M, Fitzgerald K, Jayaraman M, Barros S, Ansell S, Du X, Hope MJ, Madden TD, Mui BL, Semple SC, Tam YK, Ciufolini M, Witzigmann D, Kulkarni JA, van der Meel R, Cullis PR | display-authors = 6 | title = The Onpattro story and the clinical translation of nanomedicines containing nucleic acid-based drugs | journal = Nature Nanotechnology | volume = 14 | issue = 12 | pages = 1084–1087 | date = December 2019 | pmid = 31802031 | doi = 10.1038/s41565-019-0591-y | bibcode = 2019NatNa..14.1084A | s2cid = 208621038 | url = https://pure.tue.nl/ws/files/142146193/s41565_019_0591_y.pdf | access-date = 10 March 2024 | archive-date = 19 February 2024 | archive-url = https://web.archive.org/web/20240219132613/https://pure.tue.nl/ws/files/142146193/s41565_019_0591_y.pdf | url-status = live }}
Society and culture
= Economics =
As of 2020, there were 1050 people globally receiving patisiran, generating $65.5M in net-revenues for Alnylam Pharmaceuticals.{{Cite web|title=Patisiran and Vutrisiran, in development for the Treatment of Transthyretin-Mediated Amyloidosis|url=https://www.alnylam.com/wp-content/uploads/2020/09/2020-RNAi-Roundtable_TTR_FINAL.pdf|url-status=live|access-date=|website=Alnylam Pharmaceuticals|archive-date=9 October 2021|archive-url=https://web.archive.org/web/20211009070919/https://www.alnylam.com/wp-content/uploads/2020/09/2020-RNAi-Roundtable_TTR_FINAL.pdf}}{{Cite press release|date=2021-02-11|title=Alnylam Pharmaceuticals Reports Fourth Quarter and Full Year 2020 Financial Results and Highlights Recent Period Activity|url=https://www.businesswire.com/news/home/20210211005307/en/Alnylam-Pharmaceuticals-Reports-Fourth-Quarter-and-Full-Year-2020-Financial-Results-and-Highlights-Recent-Period-Activity|access-date=2021-06-23|publisher=Alnylam|via=Business Wire|archive-date=24 June 2021|archive-url=https://web.archive.org/web/20210624203159/https://www.businesswire.com/news/home/20210211005307/en/Alnylam-Pharmaceuticals-Reports-Fourth-Quarter-and-Full-Year-2020-Financial-Results-and-Highlights-Recent-Period-Activity|url-status=live}}
References
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{{Other nervous system drugs}}
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