Luspatercept

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Luspatercept
Clinical data
Pronunciation /lʌsˈpætərsɛpt/
lus-PAT-ər-sept
Trade names Reblozyl
Other namesACE-536, luspatercept-aamt
AHFS/Drugs.com Monograph
MedlinePlus a620043
License data
Pregnancy
category
Routes of
administration 		Subcutaneous injection
ATC code
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
Formula C3350H5070N906O1044S38
Molar mass 75958.99 g·mol−1

Luspatercept, sold under the brand name Reblozyl, is a medication used for the treatment of anemia in beta thalassemia and myelodysplastic syndromes. [5]

Contents

The US Food and Drug Administration (FDA) considers it to be a first-in-class medication. [8]

Medical uses

Luspatercept 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. [6]

Luspatercept is indicated for the treatment of adults with transfusion-dependent anaemia associated with beta thalassaemia. [6]

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. [9]

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. [10] It binds TGF (transforming growth factor beta) superfamily ligands to reduce SMAD signaling. The reduction in SMAD signaling leads to enhanced erythroid maturation. [9]

History

Phase III trials evaluated the efficacy of luspatercept for the treatment of anemia in the hematological disorders beta thalassemia [11] and myelodysplastic syndromes. [12]

It was developed by Acceleron Pharma in collaboration with Celgene. [13]

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. [14] [15] [16] [17] Luspatercept was approved for medical use in the European Union in June 2020. [6]

The U.S. Food and Drug Administration (FDA) awarded orphan drug status in 2013, and fast track designation in 2015. [18]

Research

Luspatercept is being evaluated for use in adults with non-transfusion dependent beta thalassemia. [19]

Related Research Articles

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Thalassemias are inherited blood disorders that result in abnormal hemoglobin. Symptoms depend on the type of thalassemia and can vary from none to severe. Often there is mild to severe anemia as thalassemia can affect the production of red blood cells and also affect how long the red blood cells live. Symptoms of anemia include feeling tired and having pale skin. Other symptoms of thalassemia include bone problems, an enlarged spleen, yellowish skin, pulmonary hypertension, and dark urine. Slow growth may occur in children. Symptoms and presentations of thalassemia can change over time. Thalassemia is also known as Cooley's anemia or Mediterranean anemia.

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<span class="mw-page-title-main">Beta thalassemia</span> Blood disorder

Beta thalassemias are a group of inherited blood disorders. They are forms of thalassemia caused by reduced or absent synthesis of the beta chains of hemoglobin that result in variable outcomes ranging from severe anemia to clinically asymptomatic individuals. Global annual incidence is estimated at one in 100,000. Beta thalassemias occur due to malfunctions in the hemoglobin subunit beta or HBB. The severity of the disease depends on the nature of the mutation.

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References

  1. 1 2 "Reblozyl". Therapeutic Goods Administration (TGA). 7 September 2021. Retrieved 17 September 2021.
  2. ↑ "AusPAR: Luspatercept". Therapeutic Goods Administration (TGA). 28 April 2022. Retrieved 28 April 2022.
  3. ↑ "Summary Basis of Decision (SBD) for Reblozyl". Health Canada. 23 October 2014. Retrieved 29 May 2022.
  4. ↑ "Health product highlights 2021: Annexes of products approved in 2021". Health Canada . 3 August 2022. Retrieved 25 March 2024.
  5. 1 2 "Reblozyl- luspatercept injection, powder, lyophilized, for solution". DailyMed. Retrieved 17 September 2021.
  6. 1 2 3 4 "Reblozyl EPAR". European Medicines Agency (EMA). 28 April 2020. Retrieved 26 September 2020. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  7. ↑ "Reblozyl Product information". Union Register of medicinal products. Retrieved 3 March 2023.
  8. ↑ "New Drug Therapy Approvals 2019". U.S. Food and Drug Administration. 31 December 2019. Retrieved 15 September 2020.
  9. 1 2 Taher AT, Musallam KM, Cappellini MD (February 2021). "β-Thalassemias". The New England Journal of Medicine. 384 (8): 727–743. doi:10.1056/NEJMra2021838. PMID   33626255. S2CID   232049825.
  10. ↑ "Luspatercept". NCI Thesaurus. National Cancer Institute.
  11. ↑ "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". clinicaltrials.gov. 21 January 2022. Retrieved 5 May 2022.
  12. ↑ "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". clinicaltrials.gov. 19 November 2021. Retrieved 5 May 2022.
  13. ↑ "Luspatercept: Our Lead Product Candidate". Acceleron Pharma. Archived from the original on 5 March 2017. Retrieved 22 May 2017.
  14. ↑ "FDA approves first therapy to treat patients with rare blood disorder". U.S. Food and Drug Administration (FDA) (Press release). 8 November 2019. Archived from the original on 13 November 2019. Retrieved 13 November 2019.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  15. ↑ "Reblozyl (luspatercept-aamt) FDA Approval History". Drugs.com. Archived from the original on 13 November 2019. Retrieved 13 November 2019.
  16. ↑ "FDA Approves Reblozyl (luspatercept-aamt) for the Treatment of Anemia in Adults With Beta Thalassemia Who Require Regular Red Blood Cell Transfusions". Celgene (Press release). 8 November 2019. Archived from the original on 13 November 2019. Retrieved 13 November 2019.
  17. ↑ "Drug Trials Snapshots: Reblozyl". U.S. Food and Drug Administration (FDA). 8 November 2019. Retrieved 26 January 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  18. ↑ "FDA Fast Track Designation Granted to Luspatercept for the Treatment of Patients with Beta-Thalassemia" (Press release). Acceleron/Celgene. 18 May 2015. Retrieved 22 May 2017– via Business Wire.
  19. ↑ Piga A, Perrotta S, Gamberini MR, Voskaridou E, Melpignano A, Filosa A, et al. (March 2019). "Luspatercept improves hemoglobin levels and blood transfusion requirements in a study of patients with β-thalassemia". Blood. 133 (12): 1279–1289. doi: 10.1182/blood-2018-10-879247 . PMC   6440118 . PMID   30617198.
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