Lumasiran

{{Short description|Medication for the treatment of primary hyperoxaluria type 1}} {{Use American English|date=October 2020}} {{Use dmy dates|date=October 2020}} {{cs1 config |name-list-style=vanc |display-authors=6}} {{Infobox drug | image = Lumasiran 02.svg | image_class = skin-invert-image | width = 300 | alt = | caption =

| legal_AU = S4 | legal_AU_comment = <ref>{{Cite web | title=OXLUMO (Medison Pharma Australia Pty Ltd) {{!}} Therapeutic Goods Administration (TGA) | url=https://www.tga.gov.au/resources/prescription-medicines-registrations/oxlumo-medison-pharma-australia-pty-ltd | archive-url=https://web.archive.org/web/20240915052807/https://www.tga.gov.au/resources/prescription-medicines-registrations/oxlumo-medison-pharma-australia-pty-ltd | access-date=2025-10-04 | archive-date=2024-09-15}}</ref><ref name="Oxlumo APMDS">{{cite web | title=Oxlumo (lumasiran) | website=Therapeutic Goods Administration (TGA) | date=10 July 2024 | url=https://www.tga.gov.au/resources/auspmd/oxlumo-lumasiran | access-date=12 October 2024}}</ref> | legal_BR =  | legal_BR_comment = | legal_CA = Rx-only | legal_CA_comment = <ref>{{Cite web |url=https://pdf.hres.ca/dpd_pm/00064948.PDF |title= Oxlumo Lumasiran Injection Product Monograph |access-date=29 June 2022 |archive-date=29 June 2022 |archive-url=https://web.archive.org/web/20220629032304/https://pdf.hres.ca/dpd_pm/00064948.PDF |url-status=live | work = Alnylam Netherlands B.V. | publisher = The Drug and Health Product Register, The Government of Canada }}</ref><ref>{{cite web | title=Summary Basis of Decision - Oxlumo | website=Health Canada | date=23 October 2014 | url=https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00590&lang=en | access-date=6 August 2022}}</ref> | legal_DE =  | legal_DE_comment = | legal_NZ =  | legal_NZ_comment = | legal_UK =  | legal_UK_comment = | legal_US = Rx-only | legal_US_comment = <ref name="Oxlumo FDA label">{{cite web | title=Oxlumo- lumasiran injection, solution | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=16985a31-f5e4-4557-9266-fc78d4bc5055 | access-date=26 December 2020 | archive-date=4 May 2022 | archive-url=https://web.archive.org/web/20220504204250/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=16985a31-f5e4-4557-9266-fc78d4bc5055 | url-status=live }}</ref><ref name="FDA PR" /> | legal_EU = Rx-only | legal_EU_comment = <ref name="Oxlumo EPAR">{{cite web | title=Oxlumo EPAR | website=European Medicines Agency (EMA) | date=13 October 2020 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/oxlumo | access-date=26 December 2020 | archive-date=10 January 2021 | archive-url=https://web.archive.org/web/20210110093434/https://www.ema.europa.eu/en/medicines/human/EPAR/oxlumo | url-status=live }}</ref><ref>{{cite web | title=Oxlumo Product information | website=Union Register of medicinal products | url=https://ec.europa.eu/health/documents/community-register/html/h1496.htm | access-date=3 March 2023}}</ref> | legal_UN =  | legal_UN_comment = | legal_status =

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'''Lumasiran''', sold under the brand name '''Oxlumo''', is a medication for the treatment of primary hyperoxaluria type 1 (PH1).<ref name="Lumasiran PAR" /><ref name="FDA PR">{{cite press release | title=FDA Approves First Drug to Treat Rare Metabolic Disorder | website=U.S. Food and Drug Administration (FDA) | date=23 November 2020 | url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-treat-rare-metabolic-disorder | access-date=23 November 2020 | archive-date=23 November 2020 | archive-url=https://web.archive.org/web/20201123235925/http://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-treat-rare-metabolic-disorder | url-status=dead }} {{PD-notice}}</ref><ref name="FDA snapshot">{{cite web | title=Drugs Trials Snapshot: Oxlumo | website=U.S. Food and Drug Administration (FDA) | date=23 November 2020 | url=https://www.fda.gov/drugs/drug-approvals-and-databases/drugs-trials-snapshot-oxlumo | access-date=26 December 2020 | archive-date=22 December 2020 | archive-url=https://web.archive.org/web/20201222035811/https://www.fda.gov/drugs/drug-approvals-and-databases/drugs-trials-snapshot-oxlumo | url-status=live }} {{PD-notice}}</ref><ref name="D'Ambrosio_2022">{{cite journal | vauthors = D'Ambrosio V, Ferraro PM | title = Lumasiran in the Management of Patients with Primary Hyperoxaluria Type 1: From Bench to Bedside | journal = International Journal of Nephrology and Renovascular Disease | volume = 15 | issue = | pages = 197–206 | date = 2022 | pmid = 35747094 | pmc = 9211742 | doi = 10.2147/IJNRD.S293682 | doi-access = free }}</ref>

The most common side effects include injection site reactions and abdominal pain.<ref name="FDA PR" />

Lumasiran is a double-stranded small interfering ribonucleic acid (siRNA) that reduces levels of glycolate oxidase (GO) enzyme by targeting the HAO1 messenger ribonucleic acid (mRNA) in hepatocytes through RNA interference.<ref name="Lumasiran treatment protocol" /> Decreased GO enzyme levels reduce the amount of available glyoxylate, a substrate for oxalate production.<ref name="Lumasiran treatment protocol" /> This results in reduction of urinary and plasma oxalate levels, the underlying cause of disease manifestations in people with PH1.<ref name="Lumasiran treatment protocol" /> As the GO enzyme is upstream of the deficient alanine:glyoxylate aminotransferase (AGT) enzyme that causes PH1, the mechanism of action of lumasiran is independent of the underlying AGXT gene mutation.<ref name="Lumasiran treatment protocol" />

Lumasiran was approved for medical use in the European Union and in the United States in November 2020.<ref name="FDA PR" /><ref name="Oxlumo EPAR" /><ref name="Drug Approval Package">{{cite web | title=Drug Approval Package: Oxlumo | website=U.S. Food and Drug Administration (FDA) | date=21 December 2020 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214103Orig1s000TOC.cfm | access-date=17 January 2021 | archive-date=22 January 2021 | archive-url=https://web.archive.org/web/20210122053744/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214103Orig1s000TOC.cfm | url-status=dead }}</ref> The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.<ref>{{cite web | title=New Drug Therapy Approvals 2020 | website=U.S. Food and Drug Administration (FDA) | date=31 December 2020 | url=https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/new-drug-therapy-approvals-2020 | access-date=17 January 2021 | archive-date=18 January 2021 | archive-url=https://web.archive.org/web/20210118011953/https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/new-drug-therapy-approvals-2020 | url-status=dead }} {{PD-notice}}</ref><ref name="Scott_2021">{{cite journal | vauthors = Scott LJ, Keam SJ | title = Lumasiran: First Approval | journal = Drugs | volume = 81 | issue = 2 | pages = 277–282 | date = February 2021 | pmid = 33405070 | doi = 10.1007/s40265-020-01463-0 | s2cid = 230783803 }}</ref>

== Medical uses == Lumasiran is indicated for the treatment of primary hyperoxaluria type 1 (PH1) in adults and children of all ages.<ref name="Lumasiran PAR" /><ref name="FDA snapshot" />

PH1 is a rare illness that causes the liver to produce an excessive amount of oxalate.<ref name="Lumasiran PAR" /><ref name="FDA snapshot" /> Oxalate is removed by the kidneys and through the urine.<ref name="Lumasiran PAR" /> In people with PH1, the extra oxalate can cause kidney stones and kidney failure.<ref name="Lumasiran PAR" /><ref name="FDA snapshot" /> The extra oxalate can also build up, and damage other parts of the body, including eyes, heart, skin, and bone.<ref name="Lumasiran PAR" /><ref name="FDA snapshot" /> This is called 'oxalosis'.<ref name="Lumasiran PAR" />

== History == Lumasiran was evaluated by the U.S. Food and Drug Administration (FDA) in two studies of participants with PH1: a randomized, placebo-controlled trial in participants six years and older and an open-label study in participants younger than six years (NCT03681184 and NCT03905694).<ref name="FDA PR" /><ref name="FDA snapshot" /> Participants ranged in age from four months to 61 years at the first dose.<ref name="FDA PR" /> In the first study, 26 participants received a monthly injection of lumasiran followed by a maintenance dose every three months; 13 participants received placebo injections.<ref name="FDA PR" /> Neither the patients nor the healthcare providers knew which treatment was being given until after the trial was completed.<ref name="FDA snapshot" /> The primary endpoint was the amount of oxalate measured in the urine over 24 hours.<ref name="FDA PR" /><ref name="FDA snapshot" /> In the lumasiran group, participants had, on average, a 65% reduction of oxalate in the urine, compared to an average 12% reduction in the placebo group.<ref name="FDA PR" /> By the sixth month of the study, 52% of participants treated with lumasiran reached a normal 24-hour urinary oxalate level; no participants treated with the placebo did.<ref name="FDA PR" /> In the second study, 16 participants younger than six years all received lumasiran.<ref name="FDA PR" /> Using another measure of oxalate in the urine, the study showed, on average, a 71% decrease in urinary oxalate by the sixth month of the study.<ref name="FDA PR" /> The trials were conducted at 25 centers in the United States, Europe, and the Middle East.<ref name="FDA snapshot" />

The FDA granted the application for lumasiran orphan drug and breakthrough therapy designations.<ref name="FDA PR" /> In addition, the manufacturer received a rare pediatric disease priority review voucher.<ref name="FDA PR" /> The FDA granted the approval of Oxlumo to Alnylam Pharmaceuticals, Inc.<ref name="FDA PR" />

== Society and culture == ===Legal status === Lumasiran is available under the UK Early Access to Medicines Scheme (EAMS) as of July 2020.<ref name="Lumasiran PAR">{{cite web | url=https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/899859/Lumasiran_Public_Assessment_Report_PAR.pdf | title=Lumasiran: Public Assessment Report (PAR) | publisher=Medicines and Healthcare products Regulatory Agency (MHRA) | access-date=17 October 2020 | archive-date=21 October 2020 | archive-url=https://web.archive.org/web/20201021091545/https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/899859/Lumasiran_Public_Assessment_Report_PAR.pdf | url-status=live }} Contains public sector information licensed under the Open Government Licence v3.0.</ref><ref name="Lumasiran treatment protocol">{{cite web | url=https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/906983/Lumasiran_Treatment_protocol_Information_for_healthcare_professionals.pdf | title=Lumasiran: Treatment protocol: Information for healthcare professionals | publisher=Medicines and Healthcare products Regulatory Agency (MHRA) | access-date=17 October 2020 | archive-date=19 October 2020 | archive-url=https://web.archive.org/web/20201019022243/https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/906983/Lumasiran_Treatment_protocol_Information_for_healthcare_professionals.pdf | url-status=live }} Contains public sector information licensed under the Open Government Licence v3.0.</ref><ref>{{cite press release | title=Alnylam Announces that the United Kingdom's MHRA Grants Early Access to Lumasiran | website=Alnylam Pharmaceuticals, Inc. | date=13 July 2020 | url=https://investors.alnylam.com/press-release?id=25011 | access-date=17 October 2020 | archive-date=18 October 2020 | archive-url=https://web.archive.org/web/20201018041651/https://investors.alnylam.com/press-release?id=25011 | url-status=live }}</ref>

On 15 October 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Oxlumo, intended for the treatment of primary hyperoxaluria type 1 (PH1).<ref name="Oxlumo: Pending EC decision">{{cite web | title=Oxlumo: Pending EC decision | website=European Medicines Agency (EMA) | date=16 October 2020 | url=https://www.ema.europa.eu/en/medicines/human/summaries-opinion/oxlumo | access-date=16 October 2020 | archive-date=18 October 2020 | archive-url=https://web.archive.org/web/20201018081511/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/oxlumo | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref><ref>{{cite press release | title=First treatment for rare condition primary hyperoxaluria type 1 | website=European Medicines Agency (EMA) | date=15 October 2020 | url=https://www.ema.europa.eu/en/news/first-treatment-rare-condition-primary-hyperoxaluria-type-1 | access-date=16 October 2020 | archive-date=18 October 2020 | archive-url=https://web.archive.org/web/20201018004625/https://www.ema.europa.eu/en/news/first-treatment-rare-condition-primary-hyperoxaluria-type-1 | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> The applicant for this medicinal product is Alnylam Netherlands B.V.<ref name="Oxlumo: Pending EC decision" />

Lumasiran was approved for medical use in the European Union and in the United States in November 2020.<ref name="FDA PR" /><ref name="Oxlumo EPAR" /><ref name="Drug Approval Package" />

== References == {{reflist}}

== External links == * {{ClinicalTrialsGov|NCT03681184|A Study to Evaluate Lumasiran in Children and Adults With Primary Hyperoxaluria Type 1 (ILLUMINATE-A)}} * {{ClinicalTrialsGov|NCT03681184|A Study of Lumasiran in Infants and Young Children With Primary Hyperoxaluria Type 1 (ILLUMINATE-B)}}

Category:Orphan drugs Category:small interfering RNA