View source for Tofersen

{{Short description|Medication}}
{{Use American English|date=April 2023}}
{{Use dmy dates|date=September 2024}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Infobox drug
| image             = Tofersen.svg
| width             = 300
| alt               =
| caption           =
<!-- Clinical data -->
| pronounce         =
| tradename         = Qalsody
| Drugs.com         = {{drugs.com|monograph|tofersen}}
| MedlinePlus       = a623024
| DailyMedID        = Tofersen
| pregnancy_AU      = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_AU_comment =
| pregnancy_category=
| routes_of_administration = [[Intrathecal]]
| ATC_prefix        = N07
| ATC_suffix        = XX22
<!-- Legal status -->
| legal_AU          = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled -->
| legal_AU_comment  =
| legal_BR          = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment  =
| legal_CA          = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_CA_comment  =
| legal_DE          = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment  =
| legal_NZ          = <!-- Class A, B, C -->
| legal_NZ_comment  =
| legal_UK          = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->
| legal_UK_comment  =
| legal_US          = Rx-only
| legal_US_comment  = <ref name="Qalsody FDA label">{{cite web | title=Qalsody- tofersen injection | website=DailyMed | date=25 April 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=81356b45-1cb7-4eef-88ea-e44cc18b47c5 | access-date=10 June 2023 | archive-date=8 May 2023 | archive-url=https://web.archive.org/web/20230508092955/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=81356b45-1cb7-4eef-88ea-e44cc18b47c5 | url-status=live }}</ref><ref name="FDA Qalsody">{{cite press release | title=FDA approves treatment of amyotrophic lateral sclerosis associated with a mutation in the SOD1 gene | publisher=U.S. [[Food and Drug Administration]] (FDA) | date=25 April 2023 | url=https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-amyotrophic-lateral-sclerosis-associated-mutation-sod1-gene | access-date=25 April 2023 | archive-date=25 April 2023 | archive-url=https://web.archive.org/web/20230425172813/https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-amyotrophic-lateral-sclerosis-associated-mutation-sod1-gene | url-status=live }} {{PD-notice}}</ref>
| legal_EU          = Rx-only
| legal_EU_comment  = <ref name="Qalsody EPAR" /><ref name="Qalsody PI" />
| legal_UN          = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment  =
| legal_status      = <!-- For countries not listed above -->
<!-- Pharmacokinetic data -->
| bioavailability   =
| protein_bound     =
| metabolism        =
| metabolites       =
| onset             =
| elimination_half-life =
| duration_of_action=
| excretion         =
<!-- Identifiers -->
| CAS_number        = 2088232-70-4
| PubChem           =
| DrugBank          = DB14782
| UNII              = 2NU6F9601K
| KEGG              = D11811
<!-- Chemical and physical data -->
| IUPAC_name        =
| C = 230 | H = 317 | N = 72 | O = 123 | P = 19 | S = 15
}}
'''Tofersen''', sold under the brand name '''Qalsody''', is a [[medication]] used for the treatment of [[amyotrophic lateral sclerosis]] (ALS).<ref name="FDA Qalsody" /> Tofersen is an [[antisense oligonucleotide]] that targets the production of [[superoxide dismutase 1]], an enzyme whose mutant form is commonly associated with amyotrophic lateral sclerosis. It is administered as an [[intrathecal]] injection.<ref name="FDA Qalsody" />
The most common side effects include fatigue, arthralgia (joint pain), increased cerebrospinal (brain and spinal cord) fluid white blood cells, and myalgia (muscle pain).<ref name="FDA Qalsody" />
Tofersen was approved for medical use in the United States in April 2023,<ref name="FDA Qalsody" /><ref>{{cite press release | title=FDA Grants Accelerated Approval for Qalsody (tofersen) for SOD1-ALS, a Major Scientific Advancement as the First Treatment to Target a Genetic Cause of ALS | publisher=Biogen | via=GlobeNewswire | date=25 April 2023 | url=https://www.globenewswire.com/news-release/2023/04/25/2654404/0/en/FDA-Grants-Accelerated-Approval-for-QALSODY-tofersen-for-SOD1-ALS-a-Major-Scientific-Advancement-as-the-First-Treatment-to-Target-a-Genetic-Cause-of-ALS.html | access-date=25 April 2023 | archive-date=25 April 2023 | archive-url=https://web.archive.org/web/20230425191620/https://www.globenewswire.com/news-release/2023/04/25/2654404/0/en/FDA-Grants-Accelerated-Approval-for-QALSODY-tofersen-for-SOD1-ALS-a-Major-Scientific-Advancement-as-the-First-Treatment-to-Target-a-Genetic-Cause-of-ALS.html | url-status=live }}</ref> and in the European Union in May 2024.<ref name="Qalsody EPAR" /> The US [[Food and Drug Administration]] (FDA) considers it to be a [[first-in-class medication]].<ref name="New Drug Therapy Approvals 2023">{{cite report | title=New Drug Therapy Approvals 2023 | website=U.S. [[Food and Drug Administration]] (FDA) | date=January 2024 | url=https://www.fda.gov/media/175253/download | format=PDF | access-date=9 January 2024 | archive-url=https://web.archive.org/web/20240110032419/https://www.fda.gov/media/175253/download | archive-date=10 January 2024 | url-status=live }}</ref>
== Medical uses ==
Tofersen is [[indicated]] to treat people with amyotrophic lateral sclerosis (ALS) associated with a mutation in the superoxide dismutase 1 (SOD1) gene (SOD1-ALS).<ref name="FDA Qalsody" />
==History==
Tofersen was developed by [[Ionis Pharmaceuticals]] and was licensed to, and co-developed by, [[Biogen]].<ref>{{cite news|last=Liu|first=Angus|date=1 May 2019|title=Biogen's antisense ALS drug shows promise in early clinical trial|url=https://www.fiercebiotech.com/research/biogen-s-antisense-als-drug-shows-promise-early-clinical-study|work=[[FierceBiotech]]|access-date=25 April 2023|archive-date=2 February 2023|archive-url=https://web.archive.org/web/20230202115409/https://www.fiercebiotech.com/research/biogen-s-antisense-als-drug-shows-promise-early-clinical-study|url-status=live }}</ref><ref>{{cite news |last=Langreth|first=Robert|date=22 March 2023|title=Biogen's ALS Drug Gets Partial Backing From FDA Panel|url=https://www.bloomberg.com/news/articles/2023-03-22/biogen-s-als-drug-tofersen-gets-partial-backing-from-fda-panel|work=[[Bloomberg News]]|access-date=25 April 2023 }}</ref>
The effectiveness of tofersen was evaluated in a 28-week, randomized, double-blind, placebo-controlled clinical study in 147 participants with weakness attributable to amyotrophic lateral sclerosis and a superoxide dismutase 1 (SOD-1) mutation confirmed by a central laboratory.<ref name="FDA Qalsody" /> The study randomly assigned 108 participants in a 2:1 ratio to receive treatment with either tofersen 100 mg (n = 72) or placebo (n = 36) for 24 weeks (three loading doses followed by five maintenance doses).<ref name="FDA Qalsody" /> The participants were approximately 43% female; 57% male; 64% White; and 8% Asian.<ref name="FDA Qalsody" /> The average age was 49.8 years (range from 23 to 78 years).<ref name="FDA Qalsody" />
The stage III [[clinical trial]] was conducted by the Neuroscience Institute and Sheffield Institute for Translational Neuroscience (SITraN), both at the University of Sheffield.<ref>{{Cite web |date=28 April 2023 |title=FDA approves drug which helps to slow progression of rare form of MND |url=https://www.sheffield.ac.uk/news/fda-approves-drug-which-helps-slow-progression-rare-form-mnd |access-date=16 May 2024 |website=www.sheffield.ac.uk |language=en}}</ref>
The US [[Food and Drug Administration]] (FDA) granted the application for tofersen [[priority review]], [[orphan drug]], and [[Fast track (FDA)|fast track]] designations.<ref name="FDA Qalsody" /><ref name="New Drug Therapy Approvals 2023" />
== Society and culture ==
=== Economics ===
Only around 1-2% of ALS cases diagnosed in the United States each year carry the specific SOD1 mutation targeted by the drug.<ref>{{cite journal | vauthors = Berdyński M, Miszta P, Safranow K, Andersen PM, Morita M, Filipek S, Żekanowski C, Kuźma-Kozakiewicz M | title = SOD1 mutations associated with amyotrophic lateral sclerosis analysis of variant severity | journal = Scientific Reports | volume = 12 | issue = 1 | pages = 103 | date = January 2022 | pmid = 34996976 | pmc = 8742055 | doi = 10.1038/s41598-021-03891-8 | bibcode = 2022NatSR..12..103B }}</ref> Fewer than 500 patients a year are expected to be eligible for the drug, which is expected to cost over $100,000 for a year's treatment.<ref name="FDA Qalsody" /><ref>{{cite news|last=Constantino|first=Annika|date=25 April 2023|title=FDA grants accelerated approval for Biogen ALS drug that treats rare form of the disease|url=https://www.cnbc.com/2023/04/25/fda-grants-accelerated-approval-biogen-als-drug.html|work=[[CNBC]]|access-date=25 April 2023|archive-date=25 April 2023|archive-url=https://web.archive.org/web/20230425174051/https://www.cnbc.com/2023/04/25/fda-grants-accelerated-approval-biogen-als-drug.html|url-status=live }}</ref><ref>{{cite news|last=Constantino|first=Annika|date=22 March 2023|title=FDA advisors vote against effectiveness of Biogen's ALS drug for rare and aggressive form of the disease|url=https://www.cnbc.com/2023/03/22/fda-advisors-vote-against-effectiveness-of-biogen-als-drug.html|work=[[CNBC]]|access-date=25 April 2023|archive-date=10 April 2023|archive-url=https://web.archive.org/web/20230410174144/https://www.cnbc.com/2023/03/22/fda-advisors-vote-against-effectiveness-of-biogen-als-drug.html|url-status=live }}</ref><ref>{{cite news|last=Robins|first=Rebecca|date=25 April 2023|title=F.D.A. Approves Drug for Rare Form of A.L.S.|url=https://www.nytimes.com/2023/04/25/business/biogen-fda-als-drug.html|work=[[The New York Times]]|access-date=25 April 2023|archive-date=25 April 2023|archive-url=https://web.archive.org/web/20230425172634/https://www.nytimes.com/2023/04/25/business/biogen-fda-als-drug.html|url-status=live }}</ref>
== Legal status ==
In February 2024, the [[Committee for Medicinal Products for Human Use]] of the [[European Medicines Agency]] adopted a positive opinion, recommending the granting of a marketing authorization under exceptional circumstances for the medicinal product Qalsody, intended for the treatment of a type of amyotrophic lateral sclerosis caused by a defective superoxide dismutase 1 (SOD1) protein.<ref name="Qalsody EPAR" /><ref>{{cite press release | title=New treatment for rare motor neuron disease recommended for approval | website=[[European Medicines Agency]] (EMA) | date=23 February 2024 | url=https://www.ema.europa.eu/en/news/new-treatment-rare-motor-neurone-disease-recommended-approval | access-date=24 February 2024}}</ref> The applicant for this medicinal product is Biogen Netherlands B.V.<ref name="Qalsody EPAR">{{cite web | title=Qalsody EPAR | website=[[European Medicines Agency]] (EMA) | date=22 February 2024 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/qalsody | access-date=24 February 2024}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> Tofersen was approved for medical use in the European Union in May 2024.<ref name="Qalsody PI">{{cite web | title=Qalsody PI | website=Union Register of medicinal products | date=3 June 2024 | url=https://ec.europa.eu/health/documents/community-register/html/h1783.htm | access-date=7 September 2024}}</ref>
== References ==
{{reflist}}
{{Other nervous system drugs}}
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{{Authority control}}
[[Category:Amyotrophic lateral sclerosis]]
[[Category:Therapeutic gene modulation]]
[[Category:Orphan drugs]]