Luspatercept improves erythroid response in transfusion-dependent beta-thalassemia

A randomized phase 3 trial designed to evaluate luspatercept for adults with transfusion-dependent beta-thalassemia achieved its primary and key secondary endpoints, according to the agent’s manufacturers.

Luspatercept (Celgene and Acceleron) is a first-in-class erythroid maturation agent believed to regulate late-stage red blood cell maturation.

The double-blind, multicenter BELIEVE study evaluated the efficacy and safety of luspatercept plus best supportive care for adults with transfusion-dependent beta-thalassemia.

Erythroid response — defined as at least a 33% reduction from baseline in red blood cell transfusion burden, with a reduction of at least two units during the protocol-defined period of 12 consecutive weeks (week 13 to week 24) — served as the primary endpoint.

Results showed luspatercept significantly improved red blood cell transfusion burden compared with placebo.

The trial also met all key secondary endpoints, including statistically significant improvements in red blood cell transfusion burden from baseline of at least a 33% from week 37 to week 48; at least a 50% reduction during the period from week 13 to week 24; at least a 50% reduction during the period from week 37 to week 48; and a mean change in transfusion burden from week 13 to week 24.

Luspatercept’s adverse event profile appeared consistent with previously reported data.

“For decades, the management of beta-thalassemia in adults has been limited to transfusions and iron chelation. Reduction of transfusion burden represents an important step forward for patients with this rare and debilitating blood disease,” Jay Backstrom, MD, chief medical officer for Celgene, said in a press release.

As HemOnc Today previously reported, the randomized phase 3 MEDALIST study — which compared luspatercept with placebo for patients with very low-, low- or intermediate-risk myelodysplastic syndrome with chronic anemia — met its primary and key secondary endpoints. Patients in the MEDALIST trial were refractory to, intolerant of or ineligible for treatment with an erythropoietin-stimulating agent. They also were ring sideroblast positive and required frequent red blood cell transfusions.

“The BELIEVE study marks the second positive phase 3 study for luspatercept and underscores the potential of this erythroid maturation agent to impact a range of diseases associated with chronic anemia,” Habib Dable, president and CEO of Acceleron, said in the release. “We continue to explore luspatercept across our broader development programs.”

A phase 3 trial is planned to evaluate the agent as first-line treatment for patients with lower-risk myelodysplastic syndrome. Phase 2 trials are underway to evaluate luspatercept for nontransfusion-dependent beta-thalassemia and myelofibrosis.

Data from the BELIEVE and MEDALIST trials will be submitted for presentation at future medical meetings. Company officials expect to submit regulatory applications for luspatercept in the United States and Europe in the first half of next year.

A randomized phase 3 trial designed to evaluate luspatercept for adults with transfusion-dependent beta-thalassemia achieved its primary and key secondary endpoints, according to the agent’s manufacturers.

Luspatercept (Celgene and Acceleron) is a first-in-class erythroid maturation agent believed to regulate late-stage red blood cell maturation.

The double-blind, multicenter BELIEVE study evaluated the efficacy and safety of luspatercept plus best supportive care for adults with transfusion-dependent beta-thalassemia.

Erythroid response — defined as at least a 33% reduction from baseline in red blood cell transfusion burden, with a reduction of at least two units during the protocol-defined period of 12 consecutive weeks (week 13 to week 24) — served as the primary endpoint.

Results showed luspatercept significantly improved red blood cell transfusion burden compared with placebo.

The trial also met all key secondary endpoints, including statistically significant improvements in red blood cell transfusion burden from baseline of at least a 33% from week 37 to week 48; at least a 50% reduction during the period from week 13 to week 24; at least a 50% reduction during the period from week 37 to week 48; and a mean change in transfusion burden from week 13 to week 24.

Luspatercept’s adverse event profile appeared consistent with previously reported data.

“For decades, the management of beta-thalassemia in adults has been limited to transfusions and iron chelation. Reduction of transfusion burden represents an important step forward for patients with this rare and debilitating blood disease,” Jay Backstrom, MD, chief medical officer for Celgene, said in a press release.

As HemOnc Today previously reported, the randomized phase 3 MEDALIST study — which compared luspatercept with placebo for patients with very low-, low- or intermediate-risk myelodysplastic syndrome with chronic anemia — met its primary and key secondary endpoints. Patients in the MEDALIST trial were refractory to, intolerant of or ineligible for treatment with an erythropoietin-stimulating agent. They also were ring sideroblast positive and required frequent red blood cell transfusions.

“The BELIEVE study marks the second positive phase 3 study for luspatercept and underscores the potential of this erythroid maturation agent to impact a range of diseases associated with chronic anemia,” Habib Dable, president and CEO of Acceleron, said in the release. “We continue to explore luspatercept across our broader development programs.”

A phase 3 trial is planned to evaluate the agent as first-line treatment for patients with lower-risk myelodysplastic syndrome. Phase 2 trials are underway to evaluate luspatercept for nontransfusion-dependent beta-thalassemia and myelofibrosis.

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Data from the BELIEVE and MEDALIST trials will be submitted for presentation at future medical meetings. Company officials expect to submit regulatory applications for luspatercept in the United States and Europe in the first half of next year.