Luspatercept: First Approval
Luspatercept (REBLOZYL®) is an erythroid maturation agent developed by Acceleron Pharma and Celgene Corporation for the treatment of anaemia associated with myelodysplastic syndromes, myelofibrosis and beta-thalassaemia. Based primarily on the results of the phase III BELIEVE trial, subcutaneous luspatercept was recently approved in the USA for the treatment of anaemia associated with beta-thalassaemia. This article summarizes the milestones in the development of luspatercept leading to this first approval.
Compliance with Ethical Standards
The preparation of this review was not supported by any external funding.
Conflict of interest
During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the authors on the basis of scientific completeness and accuracy. A. Markham, a contracted employee of Adis International Ltd/Springer Nature, is responsible for the article content and declares no relevant conflicts of interest.
- 1.Celgene Corporation, Acceleron Pharma Inc. Celgene Corporation and Acceleron Pharma announce submission of luspatercept marketing authorization application to the European Medicines Agency (EMA) for MDS and Beta-Thalassemia [media release]. 29 Apr 2019. http://www.celgene.com.
- 4.Celgene Corporation. Reblozyl® (luspatercept-aamt): US prescribing information. 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761136lbl.pdf. Accessed 26 Nov 2019.
- 5.Bristol-Myers Squibb. Bristol-Myers Squibb and Acceleron Pharma provide update on FDA Advisory Committee for Reblozyl® (luspatercept-aamt) [media release]. 6 Dec 2019. https://news.bms.com/.
- 6.Acceleron Pharma Inc. SEC Filing Form 10-K. 2018. https://www.sec.gov/Archives/edgar/data/1280600/000128060019000012/xlrn-20181231x10k.htm. Accessed 26 Nov 2019.
- 7.Acceleron Pharma Inc., Celgene Corporation. Acceleron Pharma announces global collaboration with Celgene Corporation on ACE-536 Program [media release]. 4 Aug 2011. http://www.acceleronpharma.com.
- 8.Bristol-Myers Squibb. Bristol-Myers Squibb completes acquisition of Celgene, creating a leading Biopharma company [media release]. 20 Nov 2019. https://news.bms.com/
- 10.Martinez P, Bhasin M, Li R, et al. Luspatercept inhibits PSMAD2/3 signaling and promotes erythroid maturation through a GATA1 dependent mechanism [abstract no. S842]. HemaSphere. 2018;2(Suppl 2):370.Google Scholar
- 11.Porter J, Shah F, Drasar E, et al. The BELIEVE Trial: results of a phase 3, randomised, double-blind, placebo-controlled study of luspatercept in adult b-thalassaemia patients who require regular red blood cell (RBC) transfusions [abstract no. BSH19-PO-124]. Br J Haematol. 2019;185(Suppl 1):112–3.Google Scholar
- 13.Viprakasit V, Taher A, Hermine O, et al. Evaluating luspatercept responders in the phase 3, randomized, double-blind, placebo-controlled BELIEVE trial of luspatercept in adult beta-thalassemia patients (pts) who require regular red blood cell (RBC) transfusions [abstract no. 3545]. Blood. 2019;134(Suppl 1).CrossRefGoogle Scholar
- 15.Fenaux P, Platzbecker U, Mufti GJ, et al. The MEDALIST trial: results of a phase 3, randomized, double-blind, placebo-controlled study of luspatercept to treat anemia in patients with very low-, low-, or intermediate-risk myelodysplastic syndromes (MDS) with ring sideroblasts (RS) who require red blood cell (RBC) transfusions [abstract no. 1]. Blood. 2018;132(Suppl 1).Google Scholar
- 16.Fenaux P, Mufti GJ, Buckstein R, et al. Assessment of longer-term efficacy and safety in the phase 3, randomized, double-blind, placebo-controlled MEDALIST trial of luspatercept to treat anemia in patients (pts) with revised international prognostic scoring system (IPSS-R) very low-, low-, or intermediate-risk myelodysplastic syndromes (MDS) with ring sideroblasts (RS) who require red blood cell (RBC) transfusions [abstract no. 841]. Blood. 2019;134(Suppl 1).Google Scholar
- 17.Bristol-Myers Squibb; Acceleron Pharma Inc. Reblozyl® (luspatercept-aamt) studies evaluating treatment of anemia in rare blood diseases presented at American Society of Hematology (ASH) annual meeting [media release]. 9 Dec 2019. https://news.bms.com/.
- 18.Giagounidis A, Germing U, Gotze K, et al. Luspatercept increases hemoglobin and reduces transfusion burden in patients with lower-risk myelodysplastic syndromes (MDS): long-term results from phase 2 PACE-MDS study [abstract no. P666]. Haematologica. 2017;102(Suppl 2):264.Google Scholar
- 19.Gerds AT, Vannucchi AM, Passamonti F, et al. A phase 2 study of luspatercept in patients with myelofibrosis-associated anemia [abstract no. 557]. Blood. 2019;134(Suppl 1).Google Scholar
- 20.US Food & Drug Administration. FDA approves first therapy to treat patients with rare blood [media release]. 8 Nov 2019. https://www.fda.gov.