From ASH 2014: Promising Phase 2 Results with ACE-536 in β-Thalassemia

SAN FRANCISCO — ACE-536, a recombinant fusion protein containing modified activin receptor type IIB and IgG Fc, has shown promising results in the treatment of β-thalassemia, according to results from a preliminary Phase 2 trial presented at the ASH Annual Meeting, December 7, 2014.

The agent appears to increase hemoglobin production – counteracting the decrease in hemoglobin characteristic of β-thalassemia – by binding with ligands in the TGF-β super-family and promoting late-stage erythroid differentiation. Its mechanism of action is distinct from erythropoeitin-stimulating agents (ESAs). Typically, the researchers noted, patients with this condition do not respond well to conventional ESAs.

Lead author Antonio G. Piga, MD, of University Hospital San Luigi Gonzaga in Torino, Italy, presented preliminary results from this ongoing, phase 2, multicenter, open-label, dose-finding study, that evaluated ACE-536’s ability to stimulate more effective erythropoiesis. Of the 30 adults with β-thalassemia included, seven patients were transfusion-dependent (TD; defined as ≥4 units RBCs/8 weeks prior to baseline) and 23 were non-transfusion dependent (NTD; defined as <4 units RBCs/8 weeks prior to baseline).

Patients received subcutaneous injection of ACE-536 once every 3 weeks, for up to five doses, at sequentially increasing dose levels, with a 2-month follow-up. Dr. Piga discussed preliminary data from the first 30 patients enrolled in the first five cohorts as of July 2014.

ACE-536 led to a maximum increase in hemoglobin of ≥1.5 g/dL from baseline in seven (64%) of NTD patients in the 0.6–1.0 mg/kg cohorts, while ACE-536 significantly reduced transfusion burden (>50%) in all seven TD patients in these dose cohorts. Serum ferritin levels, as well, decreased 12 to 60 percent from baseline.

On the safety side, ACE-536 was generally well tolerated, with no serious adverse events related to the treatment. The most frequently reported adverse event included bone pain, headache, and myalgia.

Overall, these data “strongly support further evaluation of ACE-536 in patients with β-thalassemia,” the investigators wrote.  Although these results are preliminary, Dr. Piga is hopeful that they will pave the way for developing the first-ever treatment for this condition. “As no treatments are approved for β-thalassemia, we are optimistic that ongoing studies will support use of this treatment, with the goal of reducing or even eliminating blood transfusions for these patients,” he said.

Source: ACE-536 Increases Hemoglobin and Decreases Transfusion Burden and Serum Ferritin in Adults with Beta-Thalassemia: Preliminary Results from a Phase 2 Study. Abstract #53. Presented at the American Society of Hematology Annual Meeting, December 7, 2014.

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