Phase II BEYOND Trial Results Announced: Luspatercept Improves Quality of Life in Adults with Non-Transfusion-Dependent (NTD) β-Thalassemia
Jun 15, 2021 13:55
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13:55
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Recently, Bristol-Myers Squibb (NYSE: BMY) and Acceleron Pharma (NASDAQ: XLRN) jointly announced the initial data from the Phase II BEYOND clinical trial. The study aims to evaluate the world's first red blood cell maturation agent, luspatercept, in combination with best supportive care for adult patients with non-transfusion-dependent (NTD) β-thalassemia.AnemiaThe efficacy and safety of the treatment. The study results were presented at the Plenary Session of the European Hematology Association (EHA) 2021 Virtual Congress (Abstract #S101). The study results showed that,77.1% of patients treated with luspatercept achieved a hemoglobin increase (≥1.0 g/dL), compared with 0% in the placebo group. Changes in patient-reported outcomes were also associated with the hemoglobin increase. Non-transfusion-dependent β-thalassemia refers to patients with thalassemia who do not require lifelong regular red blood cell transfusions; these patients typically only require occasional or frequent transfusions during specific periods.
β-thalassemia is a hereditary blood disorder caused by hemoglobin gene defects, and is the most common autosomal recessiveHeredityOne of the diseases.According to statistics, the overall annual incidence rate among symptomatic individuals is 1 per 100,000 worldwide and 1 per 10,000 in the European Union. This disease is associated with ineffective erythropoiesis, which leads to the production of abnormal red blood cells and a reduced red blood cell count, frequently resulting in severe anemia. Under these circumstances, patients are typically weakened and may develop other complications along with serious health issues.
BEYOND is a Phase II, randomized, double-blind, placebo-controlled, multicenter study designed to evaluate the efficacy and safety of luspatercept versus placebo for the treatment of adult non-transfusion-dependent β-thalassemia. Eligible patients are those with β-thalassemia or hemoglobin (Hb) E/β-thalassemia, aged ≥18 years, who received ≤5 units of red blood cell transfusions within 24 weeks prior to randomization, with a mean baseline Hb level ≤10.0 g/dL.
In this study, 145 patients were randomized in a 2:1 ratio to receive luspatercept 1 mg/kg (titratable to 1.25 mg/kg) or placebo, administered subcutaneously every 3 weeks for ≥48 weeks. Patients in both groups continued to receive best supportive care, including red blood cell transfusions and iron chelation therapy. The primary endpoint was a mean hemoglobin (Hb) increase of ≥1.0 g/dL from baseline during any consecutive 12-week period between weeks 13 and 24 in the absence of red blood cell transfusions. Secondary endpoints included the proportion of patients maintaining transfusion independence during weeks 1–24 and achieving an Hb increase of ≥1.5 g/dL from baseline during weeks 13–24, as well as the mean change in the Tiredness/Weakness (T/W) score of the Non-Transfusion-Dependent Thalassemia Patient-Reported Outcomes (NTDT-PRO) (higher scores indicate worse quality of life [QoL]).
In the absence of red blood cell transfusions, over a consecutive 12-week period from Week 13 to Week 24, 74 of 96 patients (77.1%) treated with luspatercept achieved the primary study endpoint, defined as an increase in mean Hb of ≥1.0 g/dL from baseline, compared with 0 of 49 patients (0%) in the placebo group (P<0.0001).In the luspatercept group, 40 of 55 patients (72.7%) with a mean baseline Hb <8.5 g/dL achieved the primary endpoint, compared with 0 in the placebo group (P<0.0001). Additionally, 34 of 41 patients (82.9%) in the luspatercept group with a mean baseline Hb ≥8.5 g/dL achieved the primary endpoint, compared with 0 in the placebo group (P<0.0001). According to the key secondary endpoint results, during weeks 13–24, 50 of 96 patients (52.1%) in the luspatercept group achieved a mean increase in Hb of ≥1.5 g/dL, compared with 0 (0%) in the placebo group (P<0.0001). A total of 89.6% of patients in the luspatercept group maintained transfusion independence during weeks 1–24, compared with 67.3% in the placebo group (P=0.0013). Improvements in patient-reported QoL outcomes (fatigue and weakness) were associated with the increase in Hb.
Treatment-emergent adverse events of any grade occurring in ≥5% of patients were most commonly bone pain (luspatercept group 36.5% vs. placebo group 6.1%), headache (30.2% vs. 20.4%), and arthralgia (29.2% vs. 14.3%). Among patients treated with luspatercept, no malignant`Tumor`or reports of thrombotic events.
Luspatercept is the world's first and currently only erythroid maturation agent for the treatment of anemia associated with beta-thalassemia and lower-risk myelodysplastic syndromes, as well as other related anemias. It has reportedly been approved in the European Union, the United States, and Canada.For eligible patients, luspatercept has become an important treatment option. Luspatercept should not be used as a substitute for red blood cell transfusions in patients requiring immediate correction of anemia.
"Chronic anemia and iron overload experienced by patients with non-transfusion-dependent β-thalassemia can lead to a range of clinical complications. Therefore, there is an urgent need for treatment options," said Dr. Ali Taher, MD, FRCP, and BEYOND investigator at the American University of Beirut. "Based on the results of the BEYOND study, luspatercept demonstrates the clinical potential to sustainably increase hemoglobin levels in most patients, regardless of their baseline hemoglobin status. Additionally, luspatercept was observed to improve the quality of life in adult patients with non-transfusion-dependent β-thalassemia."
“In the BEYOND study, luspatercept significantly improved patient outcomes, which is highly encouraging to us,” said Mr. Habib Dable, President and Chief Executive Officer of Acceleron. “These data further strengthen our confidence. We firmly believe that luspatercept has the potential to become a transformative treatment option to benefit an important patient population worldwide that currently lacks better treatment options.”
“The findings presented at the EHA Congress further underscore the multiple benefits of luspatercept in treating anemia and achieving transfusion independence. Additionally, luspatercept has demonstrated potential in the treatment of non-transfusion-dependent diseases, a patient population facing a range of severe complications that often have lifelong health implications,” said Dr. Noah Berkowitz, Senior Vice President of Hematology Development at Bristol-Myers Squibb. “We will continue to collaborate with our partner Acceleron to advance the clinical development of luspatercept for anemia-related hematologic diseases.”
Note: Luspatercept has not yet been approved in mainland China.
References:
REBLOZYL Summary of Product Characteristics. Accessed May 2021.
REBLOZYL U.S. Prescribing Information. Accessed May 2021.
REBLOZYL Canada Product Monograph. Accessed May 2021.
ClinicalTrials.gov. A Study to Determine the Efficacy and Safety of Luspatercept in Adults With Non Transfusion Dependent Beta (β)-Thalassemia (BEYOND). Available at: https://www.clinicaltrials.gov/ct2/show/NCT03342404?term=BEYOND&cond=Beta-Thalassemia&rank=2. Accessed May 2021.
Galanello R, Origa R. Beta thalassemia. Orphanet Journal of Rare Diseases. 2010;5(11). Available at: https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-5-11. Accessed May 2021.
Musallam, K. M., Rivella, S., Vichinsky, E., & Rachmilewitz, E. A. (2013). Non-transfusion-dependent thalassemias. Haematologica, 98(6), 833–844. https://doi.org/10.3324/haematol.2012.066845. Accessed May 2021.
Currently, treatment options for β-thalassemia-associated anemia are limited. The primary treatment includes frequent red blood cell transfusions, which may lead to iron overload and subsequently cause severe complications such as organ damage. 5 Non-transfusion-dependent thalassemia refers to a form of thalassemia that does not require lifelong regular red blood cell transfusions for survival; these patients typically only require occasional or frequent transfusions during specific periods. Luspatercept is a first-in-class erythroid maturation agent that has been demonstrated in animal models to promote late-stage erythroid maturation. To date,Luspatercept has been approved in the United States for the treatment of adult patients with beta-thalassemia who require regular red blood cell transfusions, and for adult patients with very low- to intermediate-risk myelodysplastic syndromes with ring sideroblasts (MDS-RS) or myelodysplastic/myeloproliferative neoplasms who have failed erythropoiesis-stimulating agent therapy and require 2 or more units of red blood cell transfusions over 8 weeks.TumorAnemia associated with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) in adult patients.
BEYOND is a Phase II, randomized, double-blind, placebo-controlled, multicenter study designed to evaluate the efficacy and safety of luspatercept versus placebo for the treatment of adult non-transfusion-dependent β-thalassemia. Eligible patients are those with β-thalassemia or hemoglobin (Hb) E/β-thalassemia, aged ≥18 years, who received ≤5 units of red blood cell transfusions within 24 weeks prior to randomization, with a mean baseline Hb level ≤10.0 g/dL.
In this study, 145 patients were randomized in a 2:1 ratio to receive luspatercept 1 mg/kg (titratable to 1.25 mg/kg) or placebo, administered subcutaneously every 3 weeks for ≥48 weeks. Patients in both groups continued to receive best supportive care, including red blood cell transfusions and iron chelation therapy. The primary endpoint was a mean hemoglobin (Hb) increase of ≥1.0 g/dL from baseline during any consecutive 12-week period between weeks 13 and 24 in the absence of red blood cell transfusions. Secondary endpoints included the proportion of patients maintaining transfusion independence during weeks 1–24 and achieving an Hb increase of ≥1.5 g/dL from baseline during weeks 13–24, as well as the mean change in the Tiredness/Weakness (T/W) score of the Non-Transfusion-Dependent Thalassemia Patient-Reported Outcomes (NTDT-PRO) (higher scores indicate worse quality of life [QoL]).
In the absence of red blood cell transfusions, over a consecutive 12-week period from Week 13 to Week 24, 74 of 96 patients (77.1%) treated with luspatercept achieved the primary study endpoint, defined as an increase in mean Hb of ≥1.0 g/dL from baseline, compared with 0 of 49 patients (0%) in the placebo group (P<0.0001).In the luspatercept group, 40 of 55 patients (72.7%) with a mean baseline Hb <8.5 g/dL achieved the primary endpoint, compared with 0 in the placebo group (P<0.0001). Additionally, 34 of 41 patients (82.9%) in the luspatercept group with a mean baseline Hb ≥8.5 g/dL achieved the primary endpoint, compared with 0 in the placebo group (P<0.0001). According to the key secondary endpoint results, during weeks 13–24, 50 of 96 patients (52.1%) in the luspatercept group achieved a mean increase in Hb of ≥1.5 g/dL, compared with 0 (0%) in the placebo group (P<0.0001). A total of 89.6% of patients in the luspatercept group maintained transfusion independence during weeks 1–24, compared with 67.3% in the placebo group (P=0.0013). Improvements in patient-reported QoL outcomes (fatigue and weakness) were associated with the increase in Hb.
Treatment-emergent adverse events of any grade occurring in ≥5% of patients were most commonly bone pain (luspatercept group 36.5% vs. placebo group 6.1%), headache (30.2% vs. 20.4%), and arthralgia (29.2% vs. 14.3%). Among patients treated with luspatercept, no malignant`Tumor`or reports of thrombotic events.
Luspatercept is the world's first and currently only erythroid maturation agent for the treatment of anemia associated with beta-thalassemia and lower-risk myelodysplastic syndromes, as well as other related anemias. It has reportedly been approved in the European Union, the United States, and Canada.For eligible patients, luspatercept has become an important treatment option. Luspatercept should not be used as a substitute for red blood cell transfusions in patients requiring immediate correction of anemia.
"Chronic anemia and iron overload experienced by patients with non-transfusion-dependent β-thalassemia can lead to a range of clinical complications. Therefore, there is an urgent need for treatment options," said Dr. Ali Taher, MD, FRCP, and BEYOND investigator at the American University of Beirut. "Based on the results of the BEYOND study, luspatercept demonstrates the clinical potential to sustainably increase hemoglobin levels in most patients, regardless of their baseline hemoglobin status. Additionally, luspatercept was observed to improve the quality of life in adult patients with non-transfusion-dependent β-thalassemia."
“In the BEYOND study, luspatercept significantly improved patient outcomes, which is highly encouraging to us,” said Mr. Habib Dable, President and Chief Executive Officer of Acceleron. “These data further strengthen our confidence. We firmly believe that luspatercept has the potential to become a transformative treatment option to benefit an important patient population worldwide that currently lacks better treatment options.”
“The findings presented at the EHA Congress further underscore the multiple benefits of luspatercept in treating anemia and achieving transfusion independence. Additionally, luspatercept has demonstrated potential in the treatment of non-transfusion-dependent diseases, a patient population facing a range of severe complications that often have lifelong health implications,” said Dr. Noah Berkowitz, Senior Vice President of Hematology Development at Bristol-Myers Squibb. “We will continue to collaborate with our partner Acceleron to advance the clinical development of luspatercept for anemia-related hematologic diseases.”
Note: Luspatercept has not yet been approved in mainland China.
References:
REBLOZYL Summary of Product Characteristics. Accessed May 2021.
REBLOZYL U.S. Prescribing Information. Accessed May 2021.
REBLOZYL Canada Product Monograph. Accessed May 2021.
ClinicalTrials.gov. A Study to Determine the Efficacy and Safety of Luspatercept in Adults With Non Transfusion Dependent Beta (β)-Thalassemia (BEYOND). Available at: https://www.clinicaltrials.gov/ct2/show/NCT03342404?term=BEYOND&cond=Beta-Thalassemia&rank=2. Accessed May 2021.
Galanello R, Origa R. Beta thalassemia. Orphanet Journal of Rare Diseases. 2010;5(11). Available at: https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-5-11. Accessed May 2021.
Musallam, K. M., Rivella, S., Vichinsky, E., & Rachmilewitz, E. A. (2013). Non-transfusion-dependent thalassemias. Haematologica, 98(6), 833–844. https://doi.org/10.3324/haematol.2012.066845. Accessed May 2021.