Celgene, Acceleron’s novel anemia drug gets FDA green light for rare blood disorder

By Rajaneesh K. Gopinath, Ph.D.

Reblozyl, became the first and only erythroid maturation agent to be FDA approved for the treatment of anemia in adults with beta thalassemia who require regular blood transfusions.

Introduction

Beta thalassemia is a rare, inherited blood disorder caused due to mutations in the HBB gene on chromosome 11. It is characterized by ineffective erythropoiesis, which is an abnormally low production of healthy red blood cells (RBCs) with hemoglobin, an iron-containing protein that transports oxygen in our body. The disease severity can be classified into major, intermediate or minor, based on the presence of mutations in one or two alleles. Low levels of hemoglobin cause anemia where patients experience weakness, fatigue and more serious complications due to the lack of oxygen. Although a bone marrow transplant offers a cure in many young people, the most prevalent treatment involves lifelong regimens of multiple blood transfusions which further warrants chelation therapies in some patients who experience iron overload. Last June, Bluebird Bio’s Zynteglo received conditional approval from the European Commission to treat transfusion-dependent β-thalassemia in patients 12 years and older who have no other treatment options (1).

FDA Approval of Reblozyl

Last Friday, the U.S. Food and Drug Administration (USFDA) approved Reblozyl (luspatercept-aamt), making it the first and only FDA-approved erythroid maturation agent (2,3). The agent reduces the RBC transfusion burden in patients by regulating their late-stage RBC maturation. This approval is on the back of statistically significant data achieved in Phase 3, BELIEVE trial (NCT02604433) that evaluated the safety and efficacy of Reblozyl in treating anemic adults with beta thalassemia who require regular RBC transfusions. In the Reblozyl arm, 21.4% of patients achieved more than 33% reduction in RBC transfusion during weeks 13–24, as compared to 4.5% in the placebo arm (risk difference [95% CI]: 17.0 [10.4, 23.6], P<0.0001), thereby reaching the primary endpoint. The study also met key secondary endpoints, by reducing transfusion burden by 33% during weeks 37-48, which was achieved in 19.6% of patients in the Reblozyl® arm versus only 3.6% in the placebo arm (risk difference [95% CI]: 16.1 [9.8, 22.4], P<0.0001).

Approval History

Reblozyl was co-developed by Celgene Corporation (NASDAQ: CELG) and Acceleron Pharma Inc. (NASDAQ: XLRN) as part of a global collaboration that goes way back to 2011. Last April, they announced USFDA’s acceptance of Reblozyl’s Biologics License Application (BLA) in Myelodysplastic Syndromes (MDS) and Beta-Thalassemia (4). The drug then went on to receive both Fast Track and Orphan Drug designation by the FDA.

Both companies expressed their excitement over the news. “Today’s approval is an important milestone and underscores our continued commitment to patients with hematology disorders,” said Nadim Ahmed, President, Global Hematology and Oncology for Celgene. “There are very limited options for patients living with anemia due to beta thalassemia who are dependent on long term red blood cell transfusions. We are pleased to make Reblozyl available as a new therapy for these patients to help address their anemia, a significant clinical complication of beta thalassemia.”

“We’re thrilled that Acceleron’s first approved medicine is one with the potential to help patients with beta thalassemia, who have been in need of new treatments for this lifelong disease,” said Habib Dable, President and Chief Executive Officer of Acceleron. “We are enormously grateful to the patients, families and caregivers who participated in and supported our research. Their contributions have been essential in helping to ensure that Reblozyl would emerge successfully from our longstanding collaboration with Celgene.”

According to Reuter’s, Reblozyl would be priced at $3,441 for a 25-milligram vial and is expected to enter the market within a week of its approval (5). The FDA is currently reviewing the drug for the treatment of MDS based on the results from the Phase 3 MEDALIST trial.

References

1. https://www.nature.com/articles/d41587-019-00026-3
2. 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
3. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-luspatercept-aamt-anemia-patients-beta-thalassemia
4. https://www.drugs.com/history/reblozyl.html
5. https://www.reuters.com/article/us-celgene-fda/u-s-fda-approves-celgenes-rare-blood-disorder-drug-idUSKBN1XI25M

Author

Rajaneesh K. Gopinath