Acceleron Pharma Inc's collaboration partner, Celgene, has initiated a phase II clinical trial of sotatercept in patients with end stage renal disease on hemodialysis. Sotatercept is a novel and first-in-class activin type IIA receptor (ActRIIA) fusion protein that acts during late-stage erythropoiesis (red blood cell production) to increase the production of mature red blood cells into circulation.
Acceleron will receive a $7 million milestone payment from Celgene for the achievement of this event and is also eligible to receive future development, regulatory and commercial milestones of up to $360 million for the sotatercept programme.
"In previous clinical studies, sotatercept has shown encouraging activity by increasing red blood cells as well as bone mass in patients," said Matthew Sherman, MD, chief medical officer at Acceleron. "We believe that the distinct profile of sotatercept could benefit many patients, including those who have end stage renal disease, the most advanced stage of chronic kidney disease. We look forward to the ongoing development of this promising protein therapeutic candidate, which is also being studied in phase II trials in several rare hematologic diseases, including beta-thalassemia and myelodysplastic syndromes."
The phase II clinical trial in patients with end stage renal disease (ESRD) who are on hemodialysis is designed as a two-part study to assess the safety and efficacy of sotatercept as a therapy to treat anemia and potentially to control the adverse manifestations of chronic kidney disease mineral and bone disorder (CKD-MBD). Patients in both parts of the study must first be on a stable dose of an erythropoiesis stimulating agent (ESA) to maintain hemoglobin levels and will then be switched to treatment with sotatercept after an ESA treatment free period of approximately five days.
The first part is a dose-escalation study of intravenous (IV) and subcutaneous (SC) routes of administration of sotatercept in approximately 60 patients to evaluate pharmacokinetics, safety and tolerability. Patients in the dose escalation part of the study will be given sotatercept once every fourteen days up to a total of eight doses and followed for approximately four months after their last dose.
The first part of the study is designed to inform the dosing regimens to be tested in the second part of the clinical trial. The second part will be a randomized, controlled study of approximately 230 patients to evaluate the efficacy and safety of sotatercept versus an erythropoiesis stimulating agent (ESA). Efficacy measures for part two of the study include the change in mean hemoglobin concentration from baseline and the ability of sotatercept to maintain patients' hemoglobin levels within a target range after switching from an ESA to sotatercept. Measures of biomarkers for bone remodeling and mineral metabolism also will be studied.
Chronic Kidney Disease (CKD) is a serious condition characterized by the progressive loss of kidney function and is most often caused by diabetes or high blood pressure. CKD is classified in five stages according to the degree of kidney impairment.
Sotatercept is an activin receptor type IIA fusion protein that acts as a ligand trap for members in the Transforming Growth Factor-Beta (TGF-ß) 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. Acceleron and Celgene are jointly developing sotatercept as part of a global collaboration. Sotatercept is currently in multiple phase II clinical trials.
Acceleron is focused on the discovery, development and commercialization of novel protein therapeutics for cancer and rare diseases.