Celgene Corporation and Acceleron Pharma, Inc. recently announced they have entered into a joint development and commercialization agreement for ACE-536 for the treatment of anemia. The companies already have a collaboration around sotatercept (ACE-011) entered in 2008. Under the new agreement, the companies will collaborate to develop both products and potentially others for treating anemia across a wide range of indications.

Celgene and Acceleron will jointly develop, manufacture, and commercialize ACE-536, a novel protein therapeutic that inhibits members of the TGF-beta superfamily involved in erythropoiesis, for the treatment of anemia. Additionally, Celgene will have an option to future Acceleron programs developed for anemia. Celgene will make an upfront payment to Acceleron of $25 million.

“Acceleron has uncovered an exciting new approach to treating disorders of erythropoiesis, and we are pleased to broaden our successful partnership with Celgene,” said John Knopf, PhD, CEO of Acceleron. “Acceleron and Celgene can now combine our strengths to develop molecules to treat a broad array of under-served diseases and conditions in which patients suffer from anemia. To that end, we look forward to initiating the Phase I clinical trial of ACE-536 within the next few months. ACE-536 is our fourth internally discovered and developed drug to enter the clinic.”

“Celgene and Acceleron have a strong partnership that continues to advance innovative therapies in areas of great unmet medical need,” said Tom Daniel, PhD, President, Research, Celgene. “The work we will embark on with ACE-536 is a natural extension of our strong presence in hematology. We look forward to exploring the potential of ACE-536 for patients with anemia worldwide.”

Under the terms of the agreement, Acceleron will be responsible for conducting the Phase I and initial Phase II clinical trials, and Celgene will conduct the subsequent Phase II and Phase III clinical studies. Acceleron will manufacture ACE-536 for the Phase I and Phase II clinical trials, and Celgene will have responsibility for the manufacture of Phase III and commercial supplies. Acceleron will pay a share of the development expenses through the end of 2012, and Celgene will be responsible for development costs thereafter. Acceleron is eligible to receive development, regulatory, and commercial milestones of up to $217 million for the ACE-536 program. The companies will co-promote the products in North America. Acceleron will receive tiered double-digit royalties on worldwide net sales.

ACE-536 is a ligand trap that inhibits members of the TGF-beta superfamily involved in late stages of erythropoiesis. ACE-536 and sotatercept are biochemically distinct molecules and may have unique pharmacological attributes that enable their preferential use in particular anemia indications. In preclinical studies, ACE-536 promotes red blood cell (RBC) formation in the absence of erythropoietin (EPO) signaling, has distinct effects from EPO on RBC differentiation, and acts on a different population of progenitor blood cells than EPO during RBC development.

Sotatercept, a soluble receptor fusion protein composed of extracellular domain of the human activin receptor type IIA (ActRIIA) fused to human immunoglobulin, is a biologic therapeutic. Blocking signaling through ActRIIA may be a way to increase red blood cell production, promote bone formation, and inhibit tumor growth and metastasis. Sotatercept is the first in a novel class of anemia therapies. In Phase I clinical studies in healthy volunteers, sotatercept was generally well tolerated, and increased levels of hemoglobin and hematocrit, biomarkers of bone formation, and bone mineral density. The most common clinically significant adverse events observed included increased hemoglobin and increased hematocrit, which were pharmacologic effects of the drug, and also headache, all of which were manageable and reversible. Sotatercept is currently being studied in Phase II clinical trials in patients with chemotherapy-induced anemia and in patients with end-stage renal disease on hemodialysis.

Celgene Corporation, headquartered in Summit, NJ, is an integrated global pharmaceutical company engaged primarily in the discovery, development, and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation. Acceleron is a privately held biopharmaceutical company committed to discover, develop, manufacture, and commercialize novel protein therapeutics for orphan diseases and cancer. Acceleron’s scientific approach takes advantage of its unique insight to discover first-in-class therapies based on the TGF-beta protein superfamily. Acceleron utilizes proven biotherapeutic technologies and capitalizes on the company’s internal GMP manufacturing capability to advance its therapeutic programs rapidly and efficiently.