Luspatercept

{{Short description|Pharmaceutical drug}} {{Use dmy dates|date=April 2022}} {{Infobox drug | image = | alt = | caption =

| pronounce = {{IPAc-en||l|ʊ|s|ˈ|p|æ|t|ər|s|ɛ|p|t}}<br />{{respell|luus|PAT|ər|sept}} | tradename = Reblozyl | Drugs.com = {{drugs.com|monograph|luspatercept-aamt}} | MedlinePlus = a620043 | DailyMedID = Luspatercept | pregnancy_AU = D | pregnancy_AU_comment = <ref name="Reblozyl APM summary">{{cite web | title=Reblozyl | website=Therapeutic Goods Administration (TGA) | date=7 September 2021 | url=https://www.tga.gov.au/apm-summary/reblozyl | access-date=17 September 2021 | archive-date=18 September 2021 | archive-url=https://web.archive.org/web/20210918053531/https://www.tga.gov.au/apm-summary/reblozyl | url-status=live }}</ref> | pregnancy_category= | routes_of_administration = Subcutaneous injection | class = | ATC_prefix = B03 | ATC_suffix = XA06

| legal_AU = S4 | legal_AU_comment = <ref name="Reblozyl APM summary" /><ref>{{cite web | title=AusPAR: Luspatercept | website=Therapeutic Goods Administration (TGA) | date=28 April 2022 | url=https://www.tga.gov.au/auspar/auspar-luspatercept | access-date=28 April 2022 | archive-date=28 April 2022 | archive-url=https://web.archive.org/web/20220428073526/https://www.tga.gov.au/auspar/auspar-luspatercept | url-status=live }}</ref> | legal_BR =  | legal_BR_comment = | legal_CA = Rx-only | legal_CA_comment = / Schedule D<ref>{{cite web | title=Summary Basis of Decision (SBD) for Reblozyl | website=Health Canada | date=23 October 2014 | url=https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00507&lang=en | access-date=29 May 2022 | archive-date=28 May 2023 | archive-url=https://web.archive.org/web/20230528002016/https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00507&lang=en | url-status=live }}</ref><ref>{{cite web | title=Health product highlights 2021: Annexes of products approved in 2021 | website=Health Canada | date=3 August 2022 | url=https://www.canada.ca/en/health-canada/services/publications/drugs-health-products/health-product-highlights-2021/appendices.html | access-date=25 March 2024 | archive-date=25 March 2024 | archive-url=https://web.archive.org/web/20240325234307/https://www.canada.ca/en/health-canada/services/publications/drugs-health-products/health-product-highlights-2021/appendices.html | url-status=live }}</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="Reblozyl FDA label">{{cite web | title=Reblozyl- luspatercept injection, powder, lyophilized, for solution | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=82f4d266-3f52-41eb-86ba-0abf3cf468e8 | access-date=17 September 2021 | archive-date=18 September 2021 | archive-url=https://web.archive.org/web/20210918053532/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=82f4d266-3f52-41eb-86ba-0abf3cf468e8 | url-status=live }}</ref> | legal_EU = Rx-only | legal_EU_comment = <ref name="Reblozyl EPAR" /><ref>{{cite web | title=Reblozyl Product information | website=Union Register of medicinal products | url=https://ec.europa.eu/health/documents/community-register/html/h1452.htm | access-date=3 March 2023 | archive-date=21 March 2025 | archive-url=https://web.archive.org/web/20250321182234/https://ec.europa.eu/health/documents/community-register/html/h1452.htm | url-status=live }}</ref> | legal_UN =  | legal_UN_comment = | legal_status =

| IUPAC_name = | C=3350 | H=5070 | N=906 | O=1044 | S=38 }}

'''Luspatercept''', sold under the brand name '''Reblozyl''', is a medication used for the treatment of anemia in beta thalassemia and myelodysplastic syndromes.<ref name="Reblozyl FDA label" />

The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.<ref>{{cite web | title=New Drug Therapy Approvals 2019 | website=U.S. Food and Drug Administration | date=31 December 2019 | url=https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/new-drug-therapy-approvals-2019 | access-date=15 September 2020}}{{dead link|date=May 2025|bot=medic}}{{cbignore|bot=medic}}</ref>

== Medical uses == Luspatercept<ref>{{Cite web |title=Real-World Effectiveness of Luspatercept on Transfusion Dependence Examined by Analysis Group Researchers |url=https://www.analysisgroup.com/news-and-events/news/real-world-effectiveness-of-luspatercept-on-transfusion-dependence-examined-by-analysis-group-researchers/ |access-date=2025-04-28 |website=www.analysisgroup.com}}</ref> is indicated for the treatment of adults with transfusion-dependent anemia due to very low, low and intermediate-risk myelodysplastic syndromes (MDS) with ring sideroblasts, who had an unsatisfactory response to or are ineligible for erythropoietin-based therapy.<ref name="Reblozyl EPAR" />

Luspatercept is indicated for the treatment of adults with transfusion-dependent anaemia associated with beta thalassaemia.<ref name="Reblozyl EPAR" />

== Side effects == Possible adverse effects include temporary bone pain, joint pains (arthralgias), dizziness, elevated blood pressure (hypertension) and elevated uric acid levels (hyperuricemia). There was also an increased risk of thrombosis (blood clots) in patients who have risk factors for thrombosis who are taking luspatercept.<ref name="Taher">{{cite journal | vauthors = Taher AT, Musallam KM, Cappellini MD | title = β-Thalassemias | journal = The New England Journal of Medicine | volume = 384 | issue = 8 | pages = 727–743 | date = February 2021 | pmid = 33626255 | doi = 10.1056/NEJMra2021838 | s2cid = 232049825 }}</ref>

== Structure and mechanism == Luspatercept is a recombinant fusion protein derived from human activin receptor type IIb (ActRIIb) linked to a protein derived from immunoglobulin G.<ref>{{cite web | url = https://evsexplore.semantics.cancer.gov/evsexplore/concept/ncit/C104012 | title = Luspatercept | work = NCI Thesaurus | publisher = National Cancer Institute}}</ref> It binds TGF (transforming growth factor beta) superfamily ligands to reduce SMAD signaling. The reduction in SMAD signaling leads to enhanced erythroid maturation.<ref name="Taher" />

== History == Phase III trials evaluated the efficacy of luspatercept for the treatment of anemia in the hematological disorders beta thalassemia<ref>{{cite web |title=A Phase 3, Double-Blind, Placebo Controlled Multicenter Study to Determine the Efficacy and Safety of Luspatercept (ACE-536) in Adults With Transfusion Dependent Beta (B)-Thalassemia |url=https://www.clinicaltrials.gov/ct2/show/NCT02604433 |publisher=clinicaltrials.gov |access-date=5 May 2022 |date=21 January 2022 |archive-date=19 April 2023 |archive-url=https://web.archive.org/web/20230419092634/https://www.clinicaltrials.gov/ct2/show/NCT02604433 |url-status=live }}</ref> and myelodysplastic syndromes.<ref>{{cite web |title=A Phase 3, Double-blind, Randomized Study to Compare the Efficacy and Safety of Luspatercept (ACE-536) Versus Placebo for the Treatment of Anemia Due to the IPSS-R Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes in Subjects With Ring Sideroblasts Who Require Red Blood Cell Transfusions. |url=https://www.clinicaltrials.gov/ct2/show/NCT02631070 |publisher=clinicaltrials.gov |access-date=5 May 2022 |date=19 November 2021 |archive-date=7 June 2023 |archive-url=https://web.archive.org/web/20230607142222/https://clinicaltrials.gov/ct2/show/NCT02631070 |url-status=live }}</ref>

It was developed by Acceleron Pharma in collaboration with Celgene.<ref>{{cite web |url=http://www.acceleronpharma.com/products/luspatercept/ |title=Luspatercept: Our Lead Product Candidate |publisher=Acceleron Pharma |date= |access-date=22 May 2017 |archive-date=5 March 2017 |archive-url=https://web.archive.org/web/20170305123310/http://www.acceleronpharma.com/products/luspatercept/ |url-status=dead }}</ref>

The U.S. Food and Drug Administration (FDA) granted approval for luspatercept–aamt in November 2019, for the treatment of anemia (lack of red blood cells) in adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions.<ref name="FDA PR">{{cite press release | title=FDA approves first therapy to treat patients with rare blood disorder | website=U.S. Food and Drug Administration (FDA) | date=8 November 2019 | url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-therapy-treat-patients-rare-blood-disorder | archive-url=https://web.archive.org/web/20191113231630/https://www.fda.gov/news-events/press-announcements/fda-approves-first-therapy-treat-patients-rare-blood-disorder | archive-date=13 November 2019 | url-status=dead | access-date=13 November 2019}} {{PD-notice}}</ref><ref>{{cite web | title=Reblozyl (luspatercept-aamt) FDA Approval History | website=Drugs.com | url=https://www.drugs.com/history/reblozyl.html | archive-url=https://web.archive.org/web/20191113233045/https://www.drugs.com/history/reblozyl.html | archive-date=13 November 2019 | url-status=live | access-date=13 November 2019}}</ref><ref>{{cite press release | title=FDA Approves Reblozyl (luspatercept-aamt) for the Treatment of Anemia in Adults With Beta Thalassemia Who Require Regular Red Blood Cell Transfusions | website=Celgene | date=8 November 2019 | url=https://ir.celgene.com/press-releases/press-release-details/2019/FDA-Approves-REBLOZYL-luspatercept-aamt-for-the-Treatment-of-Anemia-in-Adults-With-Beta-Thalassemia-Who-Require-Regular-Red-Blood-Cell-Transfusions/default.aspx | archive-url=https://web.archive.org/web/20191113233542/https://ir.celgene.com/press-releases/press-release-details/2019/FDA-Approves-REBLOZYL-luspatercept-aamt-for-the-Treatment-of-Anemia-in-Adults-With-Beta-Thalassemia-Who-Require-Regular-Red-Blood-Cell-Transfusions/default.aspx | archive-date=13 November 2019 | url-status=live | access-date=13 November 2019}}</ref><ref name="FDA Snapshot">{{cite web | title=Drug Trials Snapshots: Reblozyl | website=U.S. Food and Drug Administration (FDA) | date=8 November 2019 | url=http://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-reblozyl | access-date=26 January 2020}}{{dead link|date=May 2025|bot=medic}}{{cbignore|bot=medic}} {{PD-notice}}</ref> Luspatercept was approved for medical use in the European Union in June 2020.<ref name="Reblozyl EPAR">{{cite web | title=Reblozyl EPAR | website=European Medicines Agency (EMA) | date=28 April 2020 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/reblozyl | access-date=26 September 2020 | archive-date=9 January 2021 | archive-url=https://web.archive.org/web/20210109053407/https://www.ema.europa.eu/en/medicines/human/EPAR/reblozyl | 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 U.S. Food and Drug Administration (FDA) awarded orphan drug status in 2013, and fast track designation in 2015.<ref>{{cite press release |url=http://www.businesswire.com/news/home/20150518005252/en/FDA-Fast-Track-Designation-Granted-Luspatercept-Treatment |title=FDA Fast Track Designation Granted to Luspatercept for the Treatment of Patients with Beta-Thalassemia |publisher=Acceleron/Celgene |via=Business Wire |date=18 May 2015 |access-date=22 May 2017 |archive-date=11 October 2021 |archive-url=https://web.archive.org/web/20211011100743/https://www.businesswire.com/news/home/20150518005252/en/FDA-Fast-Track-Designation-Granted-Luspatercept-Treatment |url-status=live }}</ref>

== Research == Luspatercept is being evaluated for use in adults with non-transfusion dependent beta thalassemia.<ref name="Piga BEYOND TRIAL">{{cite journal | vauthors = Piga A, Perrotta S, Gamberini MR, Voskaridou E, Melpignano A, Filosa A, Caruso V, Pietrangelo A, Longo F, Tartaglione I, Borgna-Pignatti C, Zhang X, Laadem A, Sherman ML, Attie KM | display-authors = 6 | title = Luspatercept improves hemoglobin levels and blood transfusion requirements in a study of patients with β-thalassemia | journal = Blood | volume = 133 | issue = 12 | pages = 1279–1289 | date = March 2019 | pmid = 30617198 | doi = 10.1182/blood-2018-10-879247 | pmc = 6440118 | doi-access = free }}</ref>

== References == {{reflist}}

Category:Drugs developed by Bristol Myers Squibb Category:Orphan drugs Category:Recombinant proteins