FDA Grants Priority Review to Luspatercept-aamt for Anemia in Adults With NTD Beta Thalassemia

The FDA has accepted and granted priority review to the supplemental biologics license application (sBLA) for luspatercept-aamt (Rebozyi) to treat anemia in adult patients with non-transfusion dependent (NTD) beta thalassemia, according to a press release by Bristol Myers Squibb.¹

The sBLA, which is supported by data from the phase 2 BEYOND clinical trial, has been given a Prescription Drug User Fee Act target action date of March 27, 2022.

“Patients with non-transfusion dependent beta thalassemia may not require lifelong blood transfusions for survival, but their need for effective treatment options is significant as they face a range of clinical complications due to chronic anemia and iron overload,” said Noah Berkowitz, MD, PhD, senior vice president, Hematology Development, Bristol Myers Squibb, in a press release.

In the phase 2, double-blind, randomized, placebo-controlled, multicenter BEYOND study (NCT03342404), luspatercept 1 mg/kg administered every 3 weeks was combined with best supportive care (BSC) and compared with an arm of subcutaneous placebo administered every 21 days plus BSC.²

The overall goal of the study is to determine the efficacy and safety of luspatercept. The primary end point of the study is the percentage of patients achieving erythroid response. The key secondary end points included various patient-reported outcomes, mean change from baseline in hemoglobin values in absence of transfusion, and percentage of patients with an erythroid response.

The first results from the study showed that in 145 patients, 77.7% of patients who received luspatercept achieved a hemoglobin increase compared with none of the patients in the placebo arm (P < .0001). The primary end point of ≥ 1.0 g/dL mean increase in hemoglobin was met. The study also showed positive results for the key secondary end point: 52.1% of patients in the luspatercept/BSC arm achieved a mean hemoglobin increase of ≥ 1.5 g/dL compared to baseline. In comparison, no patients in the placebo/BSC arm achieved an increase in hemoglobin from baseline (P < .0001). Notably, changes from baseline in patient-reported outcomes were associated with increases in hemoglobin.³

Overall, 89.6% of patients who were treated with luspatercept remained transfusion-free at weeks 1through 24 compared with only 67.3% of the placebo group (P = .0013).

Bone pain, headache, and arthralgia were treatment-emergent adverse events that occurred in at least 5% of patients in the BEYOND study. With luspatercept treatment, 36.5% of patients experienced bone pain versus 6.1% of the placebo arm. Headache occurred in 30,.25 of the luspatercept arm versus 20.4% of the placebo arm, and arthralgia occurred in 29.2% versus 14.3%, respectively.

Updated findings from the study will be presented during the upcoming American Society of Hematology Annual Meeting and Exposition.¹

“Reblozyl is an important therapy approved for anemia associated with beta thalassemia and lower-risk myelodysplastic syndromes in multiple countries, including the United States and within the European Union. Along with our partners at Merck, we are committed to continuing to advance our clinical program for Reblozyl and look forward to working with the FDA during its review of our application for this underserved patient population,” said Berkowitz in the press release.

_References:

_{1. U.S. 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. Accessed December 3, 2021. https://bit.ly/3G8jJpN}

_{2. A study to determine the efficacy and safety of luspatercept in adults with non transfusion dependent beta (β)-thalassemia (BEYOND). Clinicaltrials.gov. Accessed December 3, 2021. https://bit.ly/2ZRBJ8h}

_{3. 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. June 11, 2021. Accessed December 3, 2021. https://bit.ly/3xQAWkt}