View source for Biology:Onasemnogene abeparvovec

{{short description|Gene therapy medication used to treat spinal muscular atrophy}}
{{Infobox drug
| drug_name = Onasemnogene abeparvovec
| INN = 
| type = <!-- empty -->
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<!-- Clinical data -->
| pronounce =
| tradename = Zolgensma
| Drugs.com = {{drugs.com|ppa|onasemnogene-abeparvovec}}
| MedlinePlus =
| licence_CA = <!-- Health Canada may use generic or brand name (generic name preferred) -->
| licence_EU = <!-- EMA uses INN (or special INN_EMA) -->
| DailyMedID = Onasemnogene_abeparvovec
| licence_US = <!-- FDA may use generic or brand name (generic name preferred) -->
| pregnancy_AU = B2
| pregnancy_AU_comment = <ref name="Zolgensma APM summary" /><ref name="AusPAR: Onasemnogene abeparvovec" />
| pregnancy_category =
| routes_of_administration = Intravascular
| class =
| ATCvet =
| ATC_prefix = M09
| ATC_suffix = AX09
| ATC_supplemental =

<!-- Legal status -->
| legal_AU = S4
| legal_AU_comment = <ref name="Zolgensma APM summary">{{cite web | title=Zolgensma | website=Therapeutic Goods Administration (TGA) | date=10 March 2021 | url=https://www.tga.gov.au/apm-summary/zolgensma | access-date=8 September 2021 | archive-date=9 September 2021 | archive-url=https://web.archive.org/web/20210909035010/https://www.tga.gov.au/apm-summary/zolgensma | url-status=live }}</ref><ref name="AusPAR: Onasemnogene abeparvovec">{{cite web | title=AusPAR: Onasemnogene abeparvovec | website=Therapeutic Goods Administration (TGA) | date=22 April 2021 | url=https://www.tga.gov.au/auspar/auspar-onasemnogene-abeparvovec | access-date=8 September 2021 | archive-date=9 September 2021 | archive-url=https://web.archive.org/web/20210909040501/https://www.tga.gov.au/auspar/auspar-onasemnogene-abeparvovec | url-status=live }}</ref>
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F-->
| legal_BR_comment =
| legal_CA = Rx-only / Schedule D
| legal_CA_comment = <ref>{{cite web | title=Summary Basis of Decision (SBD) for Zolgensma | website=Health Canada | date=23 October 2014 | url=https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00521&lang=en | access-date=29 May 2022 | archive-date=30 May 2022 | archive-url=https://web.archive.org/web/20220530050206/https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00521&lang=en | url-status=live }}</ref>
| legal_DE = <!-- Anlage I, II, III or Unscheduled-->
| legal_DE_comment =
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment =
| legal_UK = POM
| legal_UK_comment = <ref name="EMC">{{cite web | title=Zolgensma 2 x 1013 vector genomes/mL solution for infusion - Summary of Product Characteristics (SmPC) | website=(emc) | date=30 June 2020 | url=https://www.medicines.org.uk/emc/product/11572/smpc | access-date=30 July 2020 | archive-date=28 October 2020 | archive-url=https://web.archive.org/web/20201028212724/https://www.medicines.org.uk/emc/product/11572/smpc | url-status=live }}</ref>
| legal_US = Rx-only
| legal_US_comment = <ref name="Zolgensma FDA label"/><ref name="FDA Zolgensma" />
| legal_EU = Rx-only
| legal_EU_comment = <ref name="Zolgensma EPAR">{{cite web | title=Zolgensma EPAR | website=[[Organization:European Medicines Agency|European Medicines Agency]] (EMA) | date=24 March 2020 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/zolgensma | access-date=30 July 2020 | archive-date=17 July 2020 | archive-url=https://web.archive.org/web/20200717170959/https://www.ema.europa.eu/en/medicines/human/EPAR/zolgensma | url-status=live }} Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref><ref>{{cite web | title=Zolgensma Product information | website=Union Register of medicinal products | url=https://ec.europa.eu/health/documents/community-register/html/h1443.htm | access-date=3 March 2023}}</ref>
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV-->
| legal_UN_comment =
| legal_status = Rx-only

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<!-- Identifiers -->
| CAS_number_Ref =
| CAS_number = 1922968-73-7
| CAS_supplemental =
| PubChem = 384585535
| IUPHAR_ligand =
| DrugBank_Ref =
| DrugBank = DB15528
| ChemSpiderID_Ref =
| ChemSpiderID =
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = MLU3LU3EVV
| KEGG_Ref =
| KEGG = D11559
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| NIAID_ChemDB =
| PDB_ligand =
| synonyms = AVXS-101, onasemnogene abeparvovec-xioi

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<!-- Gene therapy data -->
| gt_target_gene       = ''SMN1''
| gt_vector            = [[Biology:Adeno-associated virus|Adeno-associated virus serotype 9]]
| gt_nucleic_acid_type = 
| gt_editing_method    = 
| gt_delivery_method   = 
}}

<!-- Definition and medical uses -->
'''Onasemnogene abeparvovec''', sold under the brand name '''Zolgensma''', is a [[Biology:Gene therapy|gene therapy]] medication used to treat [[Medicine:Spinal muscular atrophy|spinal muscular atrophy]] (SMA).<ref name="Zolgensma FDA label">{{cite web|date=24 May 2019|title=Zolgensma- onasemnogene abeparvovec-xioi kit full prescribing information|url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=68cd4f06-70e1-40d8-bedb-609ec0afa471|access-date=18 November 2019|website=[[Medicine:DailyMed|DailyMed]]|archive-date=19 November 2019|archive-url=https://web.archive.org/web/20191119005222/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=68cd4f06-70e1-40d8-bedb-609ec0afa471|url-status=live}}</ref><ref name="FDA Zolgensma" /> It is used as a one-time infusion into a vein.<ref name="Zolgensma FDA label"/>

<!-- Side effects and mechanism -->
Onasemnogene abeparvovec works by providing a new copy of the gene that makes the human SMN protein.<ref name="Zolgensma FDA label"/>

The treatment must be accompanied by a course of corticosteroids of at least two months. Common side effects include vomiting and increased liver enzymes.<ref name="Zolgensma FDA label" /><ref name="Zolgensma EPAR" />

<!-- History and culture -->
Onasemnogene abeparvovec was first approved for medical use in the United States in 2019 as a treatment for children less than two years old.<ref name="FDA PR2">{{cite web|date=24 May 2019|title=FDA approves innovative gene therapy to treat pediatric patients with spinal muscular atrophy, a rare disease and leading genetic cause of infant mortality|url=https://www.fda.gov/news-events/press-announcements/fda-approves-innovative-gene-therapy-treat-pediatric-patients-spinal-muscular-atrophy-rare-disease|access-date=18 November 2019|website=U.S. [[Organization:Food and Drug Administration|Food and Drug Administration]] (FDA)|archive-date=1 September 2019|archive-url=https://web.archive.org/web/20190901145211/https://www.fda.gov/news-events/press-announcements/fda-approves-innovative-gene-therapy-treat-pediatric-patients-spinal-muscular-atrophy-rare-disease|url-status=live}} {{PD-notice}}</ref><ref name="Zolgensma FDA label" /> It was later approved in other jurisdictions with similar scope.<ref name=":0">{{Cite press release|url=https://www.novartis.com/news/media-releases/novartis-receives-approval-from-japanese-ministry-health-labour-and-welfare-zolgensma-only-gene-therapy-patients-spinal-muscular-atrophy-sma|title=Novartis receives approval from Japanese Ministry of Health, Labour and Welfare for Zolgensma the only gene therapy for patients with spinal muscular atrophy (SMA)|website=Novartis|access-date=29 March 2020}}</ref><ref>{{Cite web|last=Mueller|first=Casimir Jones SC-Lisa L.|title=First Gene Therapy Products Approved in Brazil|url=https://www.lexology.com/library/detail.aspx?g=5347d335-423c-4bb8-8746-187e126c8de8|access-date=1 June 2021|website=Lexology|date=September 2020|archive-date=2 June 2021|archive-url=https://web.archive.org/web/20210602214200/https://www.lexology.com/library/detail.aspx?g=5347d335-423c-4bb8-8746-187e126c8de8|url-status=live}}</ref><ref>{{Cite web|title=New Zolgensma data demonstrate age-appropriate development when used early, real-world benefit in older children and durability 5+ years post-treatment|url=https://www.novartis.com/news/media-releases/new-zolgensma-data-demonstrate-age-appropriate-development-when-used-early-real-world-benefit-older-children-and-durability-5-years-post-treatment|access-date=1 June 2021|website=Novartis|archive-date=2 June 2021|archive-url=https://web.archive.org/web/20210602213807/https://www.novartis.com/news/media-releases/new-zolgensma-data-demonstrate-age-appropriate-development-when-used-early-real-world-benefit-older-children-and-durability-5-years-post-treatment|url-status=live}}</ref> The approval scope in certain jurisdictions, including the European Union and Canada, is somewhat different.<ref name="Zolgensma EPAR" /><ref>{{Cite web|title=Health Canada approves Zolgensma, the one-time gene therapy for pediatric patients|url=https://www.bioquebec.com/press-releases/2021/health-canada-approves-zolgensma|access-date=1 June 2021|website=bioquebec|archive-date=2 June 2021|archive-url=https://web.archive.org/web/20210602213637/https://www.bioquebec.com/press-releases/2021/health-canada-approves-zolgensma|url-status=live}}</ref><ref>{{Cite web|date=26 May 2020|title=onasemnogene abeparvovec|url=https://cadth.ca/onasemnogene-abeparvovec|access-date=1 June 2021|website=CADTH.ca|archive-date=2 June 2021|archive-url=https://web.archive.org/web/20210602220015/https://cadth.ca/onasemnogene-abeparvovec|url-status=live}}</ref>

With an introductory price of $2.125 million per treatment, onasemnogene abeparvovec is one of the most expensive drugs in the world.

==Medical uses==
Onasemnogene abeparvovec has been developed to treat [[Medicine:Spinal muscular atrophy|spinal muscular atrophy]], a disease linked to a [[Biology:Mutation|mutation]] in the ''SMN1'' gene on chromosome 5q<ref name="FDA Zolgensma">{{cite web|url=https://www.fda.gov/vaccines-blood-biologics/zolgensma|title=Zolgensma|date=6 August 2019|website=U.S. [[Organization:Food and Drug Administration|Food and Drug Administration]] (FDA)|access-date=1 November 2019|id=STN: 125694|archive-date=19 November 2019|archive-url=https://web.archive.org/web/20191119010100/https://www.fda.gov/vaccines-blood-biologics/zolgensma|url-status=live}} {{PD-notice}}</ref> and diagnosed predominantly in young children that causes progressive loss of muscle function and frequently death. The medication is administered as an intravenous infusion.<ref name=LiverTox>{{cite book | title=LiverTox: Clinical and Research Information on Drug-Induced Liver Injury | chapter=Onasemnogene Abeparvovec | publisher=NCBI Bookshelf | date=20 August 2020 | pmid=33242238 | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK564658/ | access-date=13 August 2022 | id=Bookshelf ID: NBK564658 | archive-date=14 August 2022 | archive-url=https://web.archive.org/web/20220814025857/https://www.ncbi.nlm.nih.gov/books/NBK564658/ | url-status=live }}</ref>

The treatment is approved in the United States and certain other countries for use in children with spinal muscular atrophy up to the age of two, including at the presymptomatic stage of the disease.<ref name="FDA PR2"/> In the European Union and Canada, it is indicated for the treatment of patients with spinal muscular atrophy who either have a clinical diagnosis of spinal muscular atrophy type 1 or have up to three copies of the ''SMN2'' gene.<ref name="Zolgensma EPAR" /><ref>{{Cite news|date=16 December 2020|title=Health Canada approves Zolgensma, the one-time gene therapy for pediatric patients with spinal muscular atrophy (SMA)|work=Newswire Canada|publisher=Cision|url=https://www.newswire.ca/news-releases/health-canada-approves-zolgensma-r-the-one-time-gene-therapy-for-pediatric-patients-with-spinal-muscular-atrophy-sma-1-886604228.html|access-date=2 July 2021|archive-date=3 June 2021|archive-url=https://web.archive.org/web/20210603045310/https://www.newswire.ca/news-releases/health-canada-approves-zolgensma-r-the-one-time-gene-therapy-for-pediatric-patients-with-spinal-muscular-atrophy-sma-1-886604228.html|url-status=live}}</ref>

The medication is used with corticosteroids in an effort to [[Medicine:Hepatoprotection|protect the liver]].<ref name="Zolgensma FDA label"/>

==Adverse effects==
Common adverse reactions may include nausea and elevated liver enzymes.<ref name="Zolgensma FDA label"/> Serious adverse reactions may include liver problems and low platelets.<ref name="Zolgensma FDA label"/> Transient elevated levels of cardiac troponin‑I were observed in clinical trials; the clinical importance of these findings is not known.<ref name="Zolgensma FDA label" /> However, cardiac toxicity was seen in studies of other animals.<ref name="Zolgensma FDA label" />

As the medication may reduce the platelet count, platelets may need to be checked before the medication is started, then weekly for the first month and every two weeks for the next two months until the level is back to baseline.<ref name="Zolgensma FDA label"/> Liver function should be monitored for three months after administration.<ref>{{cite press release|url=https://www.fda.gov/news-events/press-announcements/fda-approves-innovative-gene-therapy-treat-pediatric-patients-spinal-muscular-atrophy-rare-disease|title=FDA approves innovative gene therapy to treat pediatric patients with spinal muscular atrophy, a rare disease and leading genetic cause of infant mortality|date=11 September 2019|website=U.S. [[Organization:Food and Drug Administration|Food and Drug Administration]] (FDA)|access-date=18 November 2019|archive-date=1 September 2019|archive-url=https://web.archive.org/web/20190901145211/https://www.fda.gov/news-events/press-announcements/fda-approves-innovative-gene-therapy-treat-pediatric-patients-spinal-muscular-atrophy-rare-disease|url-status=live}} {{PD-notice}}</ref>

==Mechanism of action==
SMA is a neuromuscular disorder caused by a [[Biology:Mutation|mutation]] in the ''SMN1'' gene, which leads to a decrease in SMN protein, a protein necessary for survival of motor neurons. Onasemnogene abeparvovec is a biologic drug consisting of [[Biology:Self-complementary adeno-associated virus|AAV9]] virus [[Biology:Capsid|capsid]]s that contains a ''SMN1'' [[Biology:Transgene|transgene]] along with synthetic [[Biology:Promoter (genetics)|promoters]].<ref name="EMC" /> Upon administration, the AAV9 viral vector delivers the ''SMN1'' transgene to the affected motor neurons, where it leads to an increase in SMN protein.{{citation needed|date=August 2021}}

==History==
Onasemnogene abeparvovec was developed by the US biotechnology startup AveXis, which was acquired by [[Company:Novartis|Novartis]] in 2018,<ref>{{Cite press release|url=https://www.novartis.com/news/media-releases/novartis-successfully-completes-acquisition-avexis-inc|title=Novartis successfully completes acquisition of AveXis, Inc.|publisher=Novartis|access-date=6 October 2018|archive-date=9 September 2019|archive-url=https://web.archive.org/web/20190909202153/https://www.novartis.com/news/media-releases/novartis-successfully-completes-acquisition-avexis-inc|url-status=live}}</ref> based on the work at the Institut de Myologie in France.<ref>{{cite press release | title=AveXis receives FDA approval for Zolgensma, the first and only gene therapy for pediatric patients with spinal muscular atrophy (SMA) | website=Novartis | date=24 May 2019 | url=https://www.novartis.com/news/media-releases/avexis-receives-fda-approval-zolgensma-first-and-only-gene-therapy-pediatric-patients-spinal-muscular-atrophy-sma | access-date=13 August 2022}}</ref>

The U.S. [[Organization:Food and Drug Administration|Food and Drug Administration]] (FDA) granted the application for onasemnogene abeparvovec-xioi fast track, [[Medicine:Breakthrough therapy|breakthrough therapy]], [[Medicine:Priority review|priority review]], and [[Chemistry:Orphan drug|orphan drug]] designations.<ref name="FDA PR2"/> The FDA also awarded the manufacturer a rare pediatric disease priority review voucher, and granted the approval of Zolgensma to AveXis Inc.<ref name="FDA PR2"/>

In June 2015, the European Commission granted orphan designation for the drug.<ref>{{cite web | title=EU/3/15/1509 | website=European Medicines Agency | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu3151509 | access-date=19 November 2019 | archive-date=19 November 2019 | archive-url=https://web.archive.org/web/20191119012740/https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu3151509 | url-status=live }}</ref> In July 2019, the drug was removed from the Committee for Medicinal Products for Human Use (CHMP) accelerated assessment program.<ref>{{cite web | title=Novartis' Zolgensma Joins Growing List of Medicines to Lose Accelerated Assessment Status in EU | website=RAPS | url=https://www.raps.org/news-and-articles/news-articles/2019/7/novartis-zolgensma-joins-growing-list-of-medicine | access-date=19 November 2019 | archive-date=19 November 2019 | archive-url=https://web.archive.org/web/20191119013546/https://www.raps.org/news-and-articles/news-articles/2019/7/novartis-zolgensma-joins-growing-list-of-medicine | url-status=live }}</ref>

In May 2019, onasemnogene abeparvovec received US FDA approval as a treatment for children less than two years old.<ref name="FDA PR2"/> Since 2019, the treatment has been reimbursed in Qatar<ref>{{Cite web|url=https://thepeninsulaqatar.com/article/20/11/2019/HMC-implements-innovative-gene-therapy-to-treat-congenital-spinal-muscular-atrophy|title=HMC implements innovative gene therapy to treat congenital spinal muscular atrophy|date=20 November 2019|website=The Peninsula|access-date=29 March 2020|archive-date=29 March 2020|archive-url=https://web.archive.org/web/20200329174230/https://thepeninsulaqatar.com/article/20/11/2019/HMC-implements-innovative-gene-therapy-to-treat-congenital-spinal-muscular-atrophy|url-status=live}}</ref> and Israel<ref>{{Cite web|url=https://www.jewishpress.com/news/health-and-medicine/in-first-worlds-most-expensive-medicine-used-to-treat-israeli-toddler/2019/11/21/|title=In First, World's Most Expensive Medicine Used to Treat Israeli Toddler|vauthors=Julian HL|access-date=29 March 2020|archive-date=29 March 2020|archive-url=https://web.archive.org/web/20200329174233/https://www.jewishpress.com/news/health-and-medicine/in-first-worlds-most-expensive-medicine-used-to-treat-israeli-toddler/2019/11/21/|url-status=live}}</ref> In March 2020, onasemnogene abeparvovec was granted regulatory approval in Japan with the label identical to the US one.<ref name=":0" /> Also in March 2020, the [[Organization:European Medicines Agency|European Medicines Agency]] recommended a conditional [[Medicine:Marketing authorization|marketing authorization]] for use in people with SMA type 1 or with any SMA type and having no more than three copies of the ''SMN2'' gene.<ref name=":1">{{Cite press release|url=https://www.ema.europa.eu/en/news/new-gene-therapy-treat-spinal-muscular-atrophy|title=New gene therapy to treat spinal muscular atrophy|date=27 March 2020|website=European Medicines Agency|access-date=29 March 2020|archive-date=29 March 2020|archive-url=https://web.archive.org/web/20200329133729/https://www.ema.europa.eu/en/news/new-gene-therapy-treat-spinal-muscular-atrophy|url-status=live}}</ref><ref name="Zolgensma EPAR" /> In May 2020, Onasemnogene abeparvovec was conditionally approved in Europe.<ref name="Zolgensma EPAR" /><ref name="EU approval">{{cite press release |title=Global Novartis News Archive |url=https://www.novartis.com/news/media-releases/avexis-receives-ec-approval-and-activates-%22day-one%22-access-program-zolgensma-only-gene-therapy-spinal-muscular-atrophy-sma |website=Novartis |access-date=20 May 2020 |archive-date=29 May 2020 |archive-url=https://web.archive.org/web/20200529202855/https://www.novartis.com/news/media-releases/avexis-receives-ec-approval-and-activates-%22day-one%22-access-program-zolgensma-only-gene-therapy-spinal-muscular-atrophy-sma |url-status=live }}</ref>

In August 2020, onasemnogene abeparvovec was granted regulatory approval in Brazil by the [[Organization:Brazilian Health Regulatory Agency|Brazilian Health Regulatory Agency]] (ANVISA).<ref>{{Cite web|title=Medicamento conhecido como mais caro do mundo recebe registro da Anvisa|url=https://g1.globo.com/ciencia-e-saude/noticia/2020/08/17/medicamento-conhecido-como-mais-caro-do-mundo-recebe-registro-da-anvisa.ghtml|access-date=18 August 2020|website=G1|language=pt-br|archive-date=31 August 2020|archive-url=https://web.archive.org/web/20200831001220/https://g1.globo.com/ciencia-e-saude/noticia/2020/08/17/medicamento-conhecido-como-mais-caro-do-mundo-recebe-registro-da-anvisa.ghtml|url-status=live}}</ref>

In December 2020, onasemnogene abeparvovec was approved for medical use in Canada.<ref>{{Cite press release|date=16 December 2020|url=https://www.newswire.ca/news-releases/health-canada-approves-zolgensma-r-the-one-time-gene-therapy-for-pediatric-patients-with-spinal-muscular-atrophy-sma-1-886604228.html|title=Health Canada approves Zolgensma, the one-time gene therapy for pediatric patients with spinal muscular atrophy (SMA)|access-date=27 May 2021|publisher=Novartis Pharmaceuticals Canada|via=[[Company:Cision|Cision]]|archive-date=3 June 2021|archive-url=https://web.archive.org/web/20210603045310/https://www.newswire.ca/news-releases/health-canada-approves-zolgensma-r-the-one-time-gene-therapy-for-pediatric-patients-with-spinal-muscular-atrophy-sma-1-886604228.html|url-status=live}}</ref><ref>{{cite web|url=https://pdf.hres.ca/dpd_pm/00059243.PDF|title=PRODUCT MONOGRAPH INCLUDING PATIENT MEDICATION INFORMATION : ZOLGENSMA|website=Pdf.hres.ca|access-date=24 March 2022|archive-date=14 June 2021|archive-url=https://web.archive.org/web/20210614123306/https://pdf.hres.ca/dpd_pm/00059243.PDF|url-status=live}}</ref>

Onasemnogene abeparvovec was approved for medical use in Australia in February 2021.<ref name="Zolgensma APM summary" /><ref name="AusPAR: Onasemnogene abeparvovec" /><ref>{{Cite web|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2021-PI-01276-1|title=TGA eBS - Product and Consumer Medicine Information Licence|website=Ebs.tga.gov.au|access-date=24 March 2022|archive-date=9 September 2021|archive-url=https://web.archive.org/web/20210909062631/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2021-PI-01276-1|url-status=live}}</ref>

An official approval in Russia was granted in December 2021.<ref>{{Cite web |title=Минздрав зарегистрировал препарат для лечения СМА «Золгенсма» |url=https://www.vedomosti.ru/society/news/2021/12/09/899915-minzdrav-zaregistriroval-preparat |access-date=2022-07-08 |website=Ведомости |language=ru |archive-date=10 December 2021 |archive-url=https://web.archive.org/web/20211210202718/https://www.vedomosti.ru/society/news/2021/12/09/899915-minzdrav-zaregistriroval-preparat |url-status=live }}</ref>

According to Singapore's Health Sciences Authority register, Zolgensma was approved on April 21.<ref>{{Cite news |last=Iau |first=Jean |date=2023-05-19 |title=Toddler with rare genetic condition can be treated after $2m raised, drug registered |language=en |work=The Straits Times |url=https://www.straitstimes.com/singapore/toddler-with-rare-genetic-condition-to-receive-treatment-after-2-mil-crowdfunding-and-drug-getting-registered |access-date=2023-05-20 |issn=0585-3923}}</ref>

==Society and culture==
=== Economics ===
The drug carries a list price of {{US$|2.125 million}} per treatment, making it the most expensive medication in the world {{as of|2019|lc=yes}}.<ref name="Guard2019">{{Cite news|url=https://www.theguardian.com/science/2019/may/25/21m-novartis-gene-therapy-to-become-worlds-most-expensive-drug|title=$2.1m Novartis gene therapy to become world's most expensive drug|date=25 May 2019|newspaper={{wipe|The Guardian}}|access-date=25 May 2019|agency=Reuters|location=London|archive-date=7 November 2020|archive-url=https://web.archive.org/web/20201107231233/https://www.theguardian.com/science/2019/may/25/21m-novartis-gene-therapy-to-become-worlds-most-expensive-drug|url-status=live}}</ref> In its first full quarter of sales {{US$|160 million}} of medication was sold.<ref name=Miller2019>{{cite news|url=https://www.reuters.com/article/us-novartis-gene-therapy/novartis-zolgensma-study-halted-by-fda-amid-safety-questions-idUSKBN1X90XS|title=Novartis' Zolgensma study halted by FDA amid safety questions|last1=Miller|first1=John|date=30 October 2019|access-date=30 October 2019|work={{wipe|Reuters}}|archive-date=30 October 2019|archive-url=https://web.archive.org/web/20191030092649/https://www.reuters.com/article/us-novartis-gene-therapy/novartis-zolgensma-study-halted-by-fda-amid-safety-questions-idUSKBN1X90XS|url-status=live}}</ref>

In Japan, the drug was made available through the public health care system on 20 May 2020, making it the most expensive drug covered by the Japanese public health care system.<ref name='pharmanews18401'>[https://answers.ten-navi.com/pharmanews/18401/ 初の「億超え新薬」ゾルゲンスマの薬価はどう決まったか] {{Webarchive|url=https://web.archive.org/web/20200815113845/https://answers.ten-navi.com/pharmanews/18401/ |date=15 August 2020 }} (Japanese). AnswersNews.</ref> The Central Social Insurance Medical Council, responsible for approving the universal drug fee schedule in Japan, has negotiated the price down to {{JPY|167,077,222}} (approx. USD {{To USD round|167077222|JPN|sf=3}}) per patient.<ref>[https://www.mhlw.go.jp/hourei/doc/hourei/H200519S0020.pdf 厚生労働省告示第二百十四号] {{Webarchive|url=https://web.archive.org/web/20201031225847/https://www.mhlw.go.jp/hourei/doc/hourei/H200519S0020.pdf |date=31 October 2020 }} (Japanese). Ministry of Health, Labour and Welfare, Japan.</ref><ref>[https://www.novartis.co.jp/sites/www.novartis.co.jp/files/pr20200520.pdf 脊髄性筋萎縮症に対する遺伝子治療用製品「ゾルゲンスマ®点滴静注」薬価基準収載のお知らせ] {{Webarchive|url=https://web.archive.org/web/20201028210704/https://www.novartis.co.jp/sites/www.novartis.co.jp/files/pr20200520.pdf |date=28 October 2020 }} (Japanese). Novartis Pharma.</ref>

===Controversy ===
In the months leading up to the medication's approval by the US [[Organization:Food and Drug Administration|Food and Drug Administration]] (FDA), a [[Social:Whistleblower|whistleblower]] informed Novartis that certain studies of the medication had been subject to data manipulation.<ref name=Erman2019>{{cite news |vauthors=Erman M |title=Novartis blames former AveXis executives for Zolgensma data manipulation |url=https://news.yahoo.com/novartis-blames-former-avexis-execs-151942378.html |access-date=26 September 2019 |agency={{wipe|Reuters}} |date=24 September 2019 |archive-date=26 September 2019 |archive-url=https://web.archive.org/web/20190926205430/https://news.yahoo.com/novartis-blames-former-avexis-execs-151942378.html |url-status=live }}</ref> Novartis fired two AveXis executives it determined responsible for the alleged data manipulation but informed the FDA of the data integrity issue only in June 2019, a month after the drug's approval.<ref name=Erman2019/> The delay drew strong condemnation from the FDA.<ref>{{cite press release | title=Statement on data accuracy issues with recently approved gene therapy | website=U.S. [[Organization:Food and Drug Administration|Food and Drug Administration]] (FDA) | date=19 November 2019 | url=https://www.fda.gov/news-events/press-announcements/statement-data-accuracy-issues-recently-approved-gene-therapy | archive-url=https://web.archive.org/web/20191119010154/https://www.fda.gov/news-events/press-announcements/statement-data-accuracy-issues-recently-approved-gene-therapy | archive-date=19 November 2019 | url-status=live | access-date=1 December 2019}} {{PD-notice}}</ref> In October 2019, the company admitted to not having informed the FDA and the [[Organization:European Medicines Agency|European Medicines Agency]] (EMA) for seven months about toxic effects of the intravenous formulation observed in laboratory animals.<ref>{{Cite news|url=https://www.reuters.com/article/us-novartis-zolgensma-idUSKBN1XB4SC|title=Novartis says delayed telling FDA of Zolgensma concern due to 'mistake'|date=1 November 2019|work=Reuters|access-date=11 November 2019|archive-date=11 November 2019|archive-url=https://web.archive.org/web/20191111185235/https://www.reuters.com/article/us-novartis-zolgensma-idUSKBN1XB4SC|url-status=live}}</ref> Due to data manipulation issue, the EMA withdrew their decision to allow an accelerated assessment of the medication.<ref>{{cite web |title=Zolgensma°: the drug of extremes |url=https://english.prescrire.org/en/6D1C355D9A772C0070646CD88C375155/Download.aspx |access-date=22 May 2020 |page=107 |date=April 2020 |archive-date=29 October 2020 |archive-url=https://web.archive.org/web/20201029001030/https://english.prescrire.org/en/6D1C355D9A772C0070646CD88C375155/Download.aspx |url-status=live }}</ref>

In December 2019, Novartis announced that it would donate 100 doses of onasemnogene abeparvovec per year to children outside the US through a global lottery. The decision, which has been claimed by Novartis to be based on a recommendation by unnamed [[Philosophy:Bioethics|bioethicists]],<ref name="R">{{cite news |url=https://www.reuters.com/article/us-novartis-gene-therapy/novartis-in-talks-with-patients-upset-about-lottery-like-gene-therapy-giveaway-idUKKBN1YO2BR |title=Novartis in talks with patients upset about lottery-like gene therapy giveaway |publisher=Reuters |date=20 December 2019 |access-date=29 May 2021 |archive-date=1 June 2021 |archive-url=https://web.archive.org/web/20210601200115/https://www.reuters.com/article/us-novartis-gene-therapy/novartis-in-talks-with-patients-upset-about-lottery-like-gene-therapy-giveaway-idUKKBN1YO2BR |url-status=live }}</ref> was received with much criticism by the European Commission,<ref>{{Cite web|url=https://www.europarl.europa.eu/doceo/document/P-9-2020-000202-ASW_EN.html|title=Answer given by Ms Kyriakides on behalf of the European Commission|vauthors=Kyriakides S|date=19 February 2020|website=European Parliament|access-date=21 April 2020|archive-date=28 October 2020|archive-url=https://web.archive.org/web/20201028212409/https://www.europarl.europa.eu/doceo/document/P-9-2020-000202-ASW_EN.html|url-status=live}}</ref> some European healthcare regulators<ref>{{Cite web|url=https://beneluxa.org/news1|title=No "lottery for life" - Statement by Beneluxa Health Ministers addressing the global managed access program designed by Novartis and Avexis|date=30 January 2020|website=Beneluxa|access-date=21 April 2020|archive-date=22 May 2020|archive-url=https://web.archive.org/web/20200522033518/https://beneluxa.org/news1|url-status=live}}</ref> and patient groups who see it as emotionally burdening, suboptimal, and ethically questionable.<ref>{{Cite web|url=https://www.sma-europe.eu/news/avxs-101-zolgensma-to-be-made-available-globally-through-a-controversial-programme/|title=AVXS-101 (Zolgensma) to be made available globally through a controversial programme|website=SMA Europe|date=26 December 2019|access-date=21 April 2020|archive-date=13 March 2020|archive-url=https://web.archive.org/web/20200313145046/https://www.sma-europe.eu/news/avxs-101-zolgensma-to-be-made-available-globally-through-a-controversial-programme/|url-status=live}}</ref> Novartis did not consult with families or doctors before announcing the scheme.<ref>{{cite news |url=https://www.theguardian.com/society/2019/dec/20/lottery-prize-zolgensma-drug-zolgensma-children-muscle-wasting-disease |title=Dismay at lottery for $2.1m drug to treat children with muscle-wasting disease |newspaper=The Guardian |date=20 December 2019 |access-date=21 December 2019 |archive-date=21 December 2019 |archive-url=https://web.archive.org/web/20191221220120/https://www.theguardian.com/society/2019/dec/20/lottery-prize-zolgensma-drug-zolgensma-children-muscle-wasting-disease |url-status=live }}</ref><ref>{{cite news |url=https://www.wsj.com/articles/novartis-to-offer-worlds-most-expensive-drug-for-free-via-lottery-11576767894 |title=Novartis to Offer World's Most Expensive Drug for Free Via Lottery |newspaper={{wipe|The Wall Street Journal}} |date=19 December 2019 |url-access=subscription |access-date=21 December 2019 |archive-date=21 December 2019 |archive-url=https://web.archive.org/web/20191221220121/https://www.wsj.com/articles/novartis-to-offer-worlds-most-expensive-drug-for-free-via-lottery-11576767894 |url-status=live }}</ref>

=== Names ===
Onasemnogene abeparvovec is the [[Medicine:International nonproprietary name|international nonproprietary name]] (INN)<ref>{{cite journal | vauthors=((World Health Organization)) | year=2018 | title=International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 79 | journal=WHO Drug Information | volume=32 | issue=1 | pages=95–6 | hdl=10665/330941 | hdl-access=free }}</ref> and the United States Adopted Name (USAN).<ref>{{cite web | title=Onasemnogene abeparvovec (USAN/INN) | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/substance/384585535 | access-date=9 September 2021 | archive-date=9 September 2021 | archive-url=https://web.archive.org/web/20210909035005/https://pubchem.ncbi.nlm.nih.gov/substance/384585535 | url-status=live }}</ref>

== References ==
{{reflist}}

== External links ==
* {{cite web| url = https://druginfo.nlm.nih.gov/drugportal/name/onasemnogene%20abeparvovec | publisher = U.S. National Library of Medicine| work = Drug Information Portal| title = Onasemnogene abeparvovec }}


{{DEFAULTSORT:Onasemnogene Abeparvovec}}
[[Category:Breakthrough therapy]]
[[Category:Experimental drugs]]
[[Category:Gene therapy]]
[[Category:Orphan drugs]]

{{Sourceattribution|Onasemnogene abeparvovec|1}}