Date: 2014-11-13
Type of information: Presentation of results at a congress
phase: 2a
Announcement: presentation of results at the American Society of Nephrology (ASN) Kidney Week 2014 meeting in Philadelphia, PA
Company: Acceleron Pharma (USA - MA)
Product: sotatercept
Action
mechanism: Sotatercept is an activin receptor type IIA fusion protein that acts as a ligand trap for members in the Transforming Growth Factor-Beta (TGF-β) superfamily involved in the late stages of erythropoiesis (red blood cell production). Sotatercept regulates late-stage erythrocyte (red blood cell) precursor cell differentiation and maturation. This mechanism of action is distinct from that of erythropoietin (EPO), which stimulates the proliferation of early-stage erythrocyte precursor cells. Sotatercept binds with high affinity to activin A and other proteins in the TGF-β superfamily and inhibits signaling through the ActRIIA receptor. In preclinical studies, administration of sotatercept or a mouse version of the molecule to mice and cynomolgus monkeys was associated with increases in erythropoiesis and total red cell mass. The precise actions of sotatercept underlying the promotion of erythropoiesis are under investigation. Acceleron and Celgene are developing sotatercept in anemia indications where the product’s unique pharmacology could potentially provide an innovative and differentiated alternative to existing anemia therapies. Celgene, is conducting the phase 2 clinical trial of sotatercept in patients with end-stage renal disease on hemodialysis.
Disease: patients with end-stage renal disease on hemodialysis
Therapeutic area: Hematological diseases - Renal diseases
Country:
Trial details:
Latest
news: * On November 13, 2014, Acceleron Pharma, a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of novel protein therapeutics for cancer and rare diseases, reported that investigators on the sotatercept program presented interim clinical data demonstrating encouraging effects of sotatercept on vascular calcification, bone mineral density, and hemoglobin levels in patients with end-stage renal disease on hemodialysis. The data were presented at the American Society of Nephrology (ASN) Kidney Week 2014 meeting in Philadelphia, PA.
Vascular Calcification: Many patients on hemodialysis suffer from rapidly increasing vascular calcification which can lead to serious and often fatal cardiovascular disease. Sotatercept slowed progression of vascular calcification in the abdominal aorta.
• Dose dependent change from baseline in total Agatston score over approximately 8 months was 58.4%, 24.9%, 17.3% and 3.4% in the placebo, 0.3, 0.5 and 0.7 mg/kg cohorts, respectively.
Renal Osteodystrophy Hemodialysis patients also suffer from renal osteodystrophy with aberrant bone metabolism characterized by increases in trabecular and decreases in cortical bone mineral density leading to increased risk of fractures. Sotatercept treatment led to decreases in trabecular and increases in cortical bone mineral density over approximately 8 months.
• Dose dependent decreases in trabecular bone mineral density
o Changes in the lumbar spine bone mineral density were 12.6%, 8.0%, 0.5% and -2.7% in the placebo, 0.3, 0.5 and 0.7 mg/kg cohorts, respectively.
• Dose dependent increases in cortical bone mineral density
o Changes in the femoral neck cortical bone mineral density were -0.9%, -1.4%, 1.6% and 3.0% in the placebo, 0.3, 0.5 and 0.7 mg/kg cohorts, respectively.
o Changes in the total hip cortical bone mineral density were -0.1%, -1.1%, 0.5% and 2.7% in the placebo, 0.3, 0.5 and 0.7 mg/kg cohorts, respectively.
Anemia: Sotatercept also produced dose dependent increases in hemoglobin in these patients on hemodialysis during the first 28-day dose cycle.
• A hemoglobin increase of ≥1.0 g/dL was achieved by 13%, 38%, 43% and 60% of the patients in the placebo, 0.3, 0.5 and 0.7 mg/kg cohorts, respectively.
• Treatment with EPO for hemoglobin levels below 9 g/dL was given to 63%, 25%, 29% and 0% of the patients in the placebo, 0.3, 0.5 and 0.7 mg/kg cohorts, respectively.
Sotatercept was generally well-tolerated and most treatment emergent adverse events were mild or moderate in severity, unrelated to study drug, relatively similar between groups, and generally consistent with subjects’ medical histories. The most common treatment emergent adverse events were fatigue, pain, constipation, nausea, viral infection, hypertension, fall, dizziness and increased blood phosphorus.
