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FDA Approves Luspatercept for Anemia Associated With Beta Thalassemia

Lisa Astor
Published Online:7:46 PM, Fri November 8, 2019
FDA logo black and whiteThe FDA has approved luspatercept-aamt (Reblozyl) for the treatment of anemia in adult patients with beta thalassemia who need regular red blood cell (RBC) transfusions.1

“Today’s approval is an important milestone and underscores our continued commitment to patients with hematology disorders,” Nadim Ahmed, president, Global Hematology and Oncology, Celgene, said in a statement. “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.” Celgene and Acceleron Pharma are jointly developing luspatercept in a global collaboration.

This approval is the first for an erythroid maturation agent, which regulates late-stage red blood cell maturation.

“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,” Habib Dable, president and CEO of Acceleron, said in a statement. “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.”

Findings from the pivotal randomized, double-blind, placebo-controlled, multicenter phase III BELIEVE trial supported the approval.

A total of 336 patients with beta thalassemia requiring regular RBC transfusions were included in the trial. In the trial, the need for regular RBC transfusions was defined as 6 to 20 RBC units every 24 weeks with no more than 35 days lasting between transfusions in that period of time. Patients were eligible to receive best supportive care during the trial, including RBC transfusions; iron-chelating agents; antibiotic, antiviral, and antifungal therapies; and/or nutritional support, as needed.

The primary endpoint of this trial was a ≥33% reduction in transfusion burden, with a reduction of ≥2 RBC units, during weeks 13 to 24, when compared with a 12-week baseline period. Secondary endpoints included ≥33% reduction in RBC transfusion burden at weeks 37 to 48, ≥50% reduction in transfusion burden at weeks 13 to 24, ≥50% reduction in transfusion burden at weeks 37 to 48, and mean change in transfusion burden at weeks 13 to 24. Moreover, achievement of ≥33% reduction in RBC transfusion burden over any consecutive 12 weeks on study was also evaluated.

Findings demonstrated that 21.4% of patients in the luspatercept arm achieved the primary endpoint compared with 4.5% of those on placebo (odds ratio, 5.79) (risk difference, 17.0; 95% CI, 10.4-23.6; P < .0001). Specifically, 19.6% patients on luspatercept achieved a ≥33% reduction in RBC transfusion burden at weeks 37 to 48 compared with 3.6% of those receiving placebo (risk difference, 16.1; 95% CI, 9.8-22.4; P <.0001).1,2

In the luspatercept arm (n = 224), 7.6% and 10.3% achieved a ≥50% reduction in RBC transfusion burden at weeks 13 to 24 and 37 to 48, respectively, versus 1.8% and 0.9% of those on placebo (P = .0303 and P = .0017, respectively), leading to a difference of mean change from baseline in transfusion burden from week 13 to week 24 was 1.35 units (P <.0001).2

Additionally, 70.5% patients who received luspatercept achieved a ≥33% RBC transfusion reduction over any consecutive 12 weeks versus 29.5% of patients in the placebo arm (P <.0001). For the other transfusion burden reduction endpoints, statistically significant differences were also observed.

Adverse events (AEs) observed in the trial that occurred more frequently with the use of luspatercept than placebo included headache (26% vs 24%, respectively), bone pain (20% vs 8%), arthralgia (19% vs 12%), fatigue (14% vs 13%), cough (14% vs 11%), abdominal pain (14% vs 12%), diarrhea (12% vs 10%) and dizziness (11% vs 5%).

Thromboembolic events, including deep vein thromboses, pulmonary embolus, portal vein thrombosis, and ischemic stroke were observed in 3.6% of patients in the luspatercept arm. Hypertension was also reported in 10.7% of patients receiving luspatercept.

Serious AEs were observed in 3.6% of patients, with 1% of these events including cerebrovascular accident and deep vein thrombosis. One patient in the trial died due to an unconfirmed case of acute myeloid leukemia.

Five percent of patients discontinued treatment with luspatercept in the trial due to AEs, most commonly due to arthralgia (1%), back pain (1%), bone pain (<1%), and headache (<1%). Dose reductions occurred in 2.7% of patients receiving luspatercept and dose interruptions occurred in 15.2%.

The FDA indicated that the recommended starting dose for luspatercept is 1 mg/kg once every 3 weeks administered subcutaneously.3
 
 
References
  1. FDA Approves REBLOZYL® (luspatercept-aamt) for the Treatment of Anemia in Adults With Beta Thalassemia Who Require Regular Red Blood Cell Transfusions [press release]. Summit, NJ & Cambridge, MA: Celgene Corporation & Acceleron Pharma Inc.; November 8, 2019. https://bwnews.pr/33t9M3a. Accessed November 8, 2019.
  2. Cappelini MD, Viprakasit V, Taher A, et al. The BELIEVE Trial: results of a phase 3, randomized, double-blind, placebo-controlled study of luspatercept in adult beta-thalassemia patients who require regular red blood cell (RBC) transfusions. Blood. 2018;132:163. doi: 10.1182/blood-2018-163.
  3. FDA approves luspatercept-aamt for anemia in patients with beta thalassemia. FDA website. Posted November 8, 2019. https://bit.ly/34JAJA0. Accessed November 8, 2019.


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