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Luspatercept increased hemoglobin, decreased transfusion requirement in beta-thalassemia
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SAN FRANCISCO – The recombinant fusion protein luspatercept increased hemoglobin levels in patients with nontransfusion-dependent beta-thalassemia, according to study results presented at the ASH Annual Meeting and Exposition.
Luspatercept (ACE-536, Acceleron Pharma) — which contains a modified activin receptor type IIB linked to the Fc protein of human immunoglobulin 1 (IgG1) — also decreased the need for transfusion and serum ferritin levels in transfusion-dependent patients with beta-thalassemia, results showed.
“This compound has demonstrated an ability to correct anemia and improve the clinical condition of thalassemia in animal models,” Antonio G. Piga, MD, of the Azienda Ospedaliero-Universitaria San Luigi Gonzaga in Turin, Italy, said during a press briefing. “It has been tested in humans in phase 1 and now phase 2, and these results in beta-thalassemia are extremely exciting.”
The analysis included 23 patients who were nontransfusion dependent — or who had received fewer than 4 units of red blood cells 8 weeks prior to baseline — who had an 8.3-g/dL mean baseline hemoglobin level. The study also included an additional seven patients who were transfusion dependent, defined by the receipt of at least 4 units of red blood cells 8 weeks prior to baseline.
The median age of patients was 34.5 years (range, 20-57), 53% were male and 83% had previously undergone splenectomy.
All patients received subcutaneous luspatercept every 3 weeks for up to five doses in 0.2-mg/kg, 0.4-mg/kg, 0.6-mg/kg, 0.8-mg/kg or 1-mg/kg doses.
The primary endpoint was a ≥1.5 g/dL hemoglobin increase for at least 2 weeks for nontransfusion-dependent patients, and a transfusion burden reduction of ≥20% over 12 weeks for transfusion-dependent patients.
Researchers noted 75% of all patients who received 0.8-mg/kg or 1-mg/kg doses of luspatercept achieved the study’s primary endpoint.
All seven transfusion-dependent patients experienced a ˃60% reduction in their transfusion burdens.
Four of five transfusion-dependent patients with iron overload at baseline had a decrease in liver iron concentration ranging from 0.7 mg/g to 4.7 mg/g at 16 weeks. All five patients exhibited 12% to 60% reductions in serum ferritin levels from baseline.
Among nontransfusion-dependent patients, eight of 12 who had iron overload at baseline experienced ≥1 mg/g decreases in liver iron concentration by 16 weeks.
One transfusion-dependent and one nontransfusion-dependent patient each experienced the resolution of long-standing leg ulcers after 3 months of treatment, Piga said.
The most common adverse events associated with luspatercept were bone pain (20%), headache (17%), myalgia (13%) and asthenia (10%). Data showed there were no changes in platelet or white blood cells, and there were no serious adverse events.
“These are preliminary results and we are very excited to start a large phase 3 trial to [confirm them],” Piga said.
For more information:
Piga AG. Abstract #53. Presented at: ASH Annual Meeting and Exposition; Dec. 6-9, 2014; San Francisco.
Disclosure: The researchers report research funding and honoraria from; board of directors/advisory roles and employment with; and equity ownership in Acceleron Pharma, ApoPharma, Celgene and Novartis.
Perspective
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Julie Panepinto, MD, MSPH
The next step for beta-thalassemia with this agent is looking at phase 3 studies. Is there really a significant improvement in anemia as they test this in a large group of patients? These are very promising data that will allow us to move forward to the next step in research.
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