The Food and Drug Administration (FDA) has accepted for Priority Review the supplemental Biologics License Application for luspatercept-aamt, an erythroid maturation agent, for the treatment of anemia in adults with nontransfusion dependent (NTD) beta thalassemia.

The application is supported by data from the randomized, double-blind, placebo-controlled phase 2 BEYOND study (ClinicalTrials.gov Identifier: NCT03342404), which evaluated the efficacy and safety of luspatercept in 145 adults with NTD beta thalassemia. Patients were randomly assigned 2:1 to receive luspatercept or placebo, in addition to best supportive care. The primary endpoint was the proportion of patients who had an increase from baseline of at least 1.0g/dL in mean of hemoglobin (Hb) values over a continuous 12-week interval from week 13 to week 24 in the absence of transfusions.

Results showed that 77.7% (n=74/96) of patients treated with luspatercept had at least a 1.0g/dL mean Hb increase from baseline vs 0% (n=0/49) of those who received placebo (P <.0001). Among those treated with luspatercept, the primary endpoint was achieved by 72.7% (n=40/55) of patients with mean baseline Hb of less than 8.5g/dL and 82.9% (n=34/41) of patients with mean baseline Hb of 8.5g/dL or higher, compared with none of the patients in the placebo group (both P<0.0001). Improvements in patient-reported quality of life outcomes were also observed with luspatercept.

The most common treatment-emergent adverse events in the luspatercept and placebo arms, respectively, were bone pain (36.5% vs 6.1%), headache (30.2% vs 20.4%), and arthralgia (29.2% vs 14.3%). There were no malignancies or thromboembolic events reported for patients treated with luspatercept.

Updated analyses from the BEYOND study will be presented at the 63rd American Society of Hematology Annual Meeting and Exposition from December 11 to 14.

A Prescription Drug User Fee Act (PDUFA) target date of March 27, 2022 has been set for the application. 

Luspatercept-aamt is currently marketed under the brand name Reblozyl® and is approved for the treatment of anemia in adults with beta thalassemia who require regular red blood cell transfusion. It is also approved for the treatment of anemia in adults with lower-risk myelodysplastic syndromes.

References

  1. US Food and Drug Administration accepts for Priority Review supplemental Biologics License Application for Reblozyl® (luspatercept-aamt) in adults with non-transfusion dependent (NTD) beta thalassemia. News release. December 3, 2021. https://www.businesswire.com/news/home/20211203005095/en/U.S.-Food-and-Drug-Administration-Accepts-for-Priority-Review-supplemental-Biologics-License-Application-for-Reblozyl%C2%AE-luspatercept-aamt-in-Adults-with-Non-Transfusion-Dependent-NTD-Beta-Thalassemia
  2. Bristol Myers Squibb and Acceleron present first results from phase 2 BEYOND study of Reblozyl® (luspatercept-aamt) in adults with non-transfusion dependent (NTD) beta thalassemia. News release. June 11, 2021. https://news.bms.com/news/corporate-financial/2021/Bristol-Myers-Squibb-and-Acceleron-Present-First-Results-from-Phase-2-BEYOND-Study-of-Reblozylluspatercept-aamt-in-Adults-with-Non-Transfusion-DependentNTDBeta-Thalassemia/default.aspx.