|Other names||ACE-536, luspatercept-aamt|
|Main uses||Low red blood cells in beta thalassemia or myelodysplastic syndrome|
|Side effects||Tiredness, headache, muscle pain, dizziness, nausea, cough, allergic reactions|
|Typical dose||1 mg/kg q 21 days|
|Chemical and physical data|
|Molar mass||75958.99 g·mol−1|
Luspatercept, sold under the brand name Reblozyl, is a medication used for the treatment of low red blood cells in beta thalassemia and myelodysplastic syndrome (MDS). In MDS it is used for cases in which the risk of blood cancer is no more than moderate and erythropoietin does not work. It is given by injection under the skin.
Common side effects include tiredness, headache, muscle pain, dizziness, nausea, cough, and allergic reactions. Other side effects may include blood clots and high blood pressure. Use in pregnancy may harm the baby. It is an erythroid maturation agent which works by blocking SMAD2 and SMAD3 pathways.
Luspatercept was approved for medical use in the United States in 2019 and Europe in 2020. In the United States it costs about 11,000 USD for 75 mg as of 2021. In Canada this amount costs about 6,600 CAD. While it is approved in the United Kingdom and Europe it is not currently available there as of 2021.
Luspatercept is used in adults with transfusion dependent beta thalassemia and was shown to reduce transfusion burden by 33% compared to placebo as well as reducing serum ferritin (storage iron) concentrations. But the medication had no significant effect with regards to decreasing liver or heart iron concentrations. 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. Luspatercept is currently being evaluated for use in adults with non-transfusion dependent beta thalassemia.
It is initially given at a dose of 1 mg/kg every 21 days.
Mechanism of action
Luspatercept is a recombinant fusion protein derived from human activin receptor type IIb (ActRIIb) linked to a protein derived from immunoglobulin G. It binds TGF (transforming growth factor beta) superfamily ligands to reduce SMAD signaling. The reduction in SMAD signaling leads to enhanced erythroid maturation.
It was developed by Acceleron Pharma in collaboration with Celgene. The U.S. Food and Drug Administration (FDA) awarded orphan drug status in 2013, and fast track designation in 2015, for both indications.
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. Luspatercept was approved for medical use in the European Union in June 2020.
- "Reblozyl- luspatercept injection, powder, lyophilized, for solution". DailyMed. Archived from the original on 18 September 2021. Retrieved 17 September 2021.
- "Reblozyl". Therapeutic Goods Administration (TGA). 7 September 2021. Archived from the original on 18 September 2021. Retrieved 17 September 2021.
- "Luspatercept-aamt Monograph for Professionals". Drugs.com. Archived from the original on 27 January 2020. Retrieved 24 November 2021.
- "Reblozyl EPAR". European Medicines Agency (EMA). 28 April 2020. Archived from the original on 9 January 2021. Retrieved 26 September 2020.
- "Reblozyl". Archived from the original on 9 January 2021. Retrieved 24 November 2021.
- "Reblozyl Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 11 October 2021. Retrieved 24 November 2021.
- "Luspatercept (Reblozyl)" (PDF). CADTH. Archived (PDF) from the original on 28 June 2021. Retrieved 24 November 2021.
- "Luspatercept". SPS - Specialist Pharmacy Service. 4 January 2016. Archived from the original on 11 December 2021. Retrieved 24 November 2021.
- 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.
- 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.
- "Luspatercept". NCI Thesaurus. National Cancer Institute. Archived from the original on 31 October 2021. Retrieved 5 October 2021.
- "Luspatercept: Our Lead Product Candidate". Acceleron Pharma. Archived from the original on 5 March 2017. Retrieved 22 May 2017.
- "FDA Fast Track Designation Granted to Luspatercept for the Treatment of Patients with Beta-Thalassemia" (Press release). Acceleron/Celgene. 18 May 2015. Archived from the original on 11 October 2021. Retrieved 22 May 2017 – via Business Wire.
- Clinical trial number NCT02604433 for "An Efficacy and Safety Study of Luspatercept (ACE-536) Versus Placebo in Adults Who Require Regular Red Blood Cell Transfusions Due to Beta (β) Thalassemia (BELIEVE)" at ClinicalTrials.gov
- Clinical trial number NCT02631070 for "A Study of Luspatercept (ACE-536) to Treat Anemia Due to Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MEDALIST)" at ClinicalTrials.gov
- "Luspatercept". AdisInsight. Archived from the original on 18 August 2017. Retrieved 1 February 2017.
- "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. This article incorporates text from this source, which is in the public domain.
- "Reblozyl (luspatercept-aamt) FDA Approval History". Drugs.com. Archived from the original on 13 November 2019. Retrieved 13 November 2019.
- "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.
- "Drug Trials Snapshots: Reblozyl". U.S. Food and Drug Administration (FDA). 8 November 2019. Archived from the original on 3 December 2020. Retrieved 26 January 2020. This article incorporates text from this source, which is in the public domain.
- "New Drug Therapy Approvals 2019". U.S. Food and Drug Administration. 31 December 2019. Archived from the original on 16 September 2020. Retrieved 15 September 2020.