Shire is shelling out $45 million up front as part of an exclusive collaboration with Acceleron Pharma centered on development of the latter’s activin receptor type IIb (ActRIIb) programs outside North America. The collaboration will focus on Acceleron’s lead neuromuscular diseases candidate, ACE-031, which is currently undergoing a Phase IIa trial for the treatment of Duchenne muscular dystrophy (DMD). Shire says ACE-031 and other ActRIIb molecules have potential utility in the treatment of other muscular and neuromuscular disorders.
The firms will jointly work on a worldwide Phase II/III development program for ACE-031. Commercial supplies of the drug for both companies will be produced at Shire’s facility in Lexington, MA. If the drug is subsequently approved, Acceleron will commercialize ACE-031 in the U.S. and Canada, and Shire retains commercialization rights for the rest of the world. Last month ACE-031 was granted both orphan-drug designation and fast-track designation by FDA for the treatment of DMD.
As part of its deal with Shire, Acceleron could receive additional development, regulatory, and sales-related milestones of up to $165 million for successful commercialization of ACE-0341 in DMD, and up to another $288 million for commercialization of other drugs and indications. Shire will also contribute to global development costs.
Shire says the deal represents an ideal fit in terms of its drug-development strategy. “Working with Acceleron on the development of ACE-031 for DMD allows us to use our expertise to help patients suffering from this devastating disease, as well as expand our pipeline into a new therapeutic area,” remarks Sylvie Grégoire, president of Shire Human Genetic Therapies.
ACE-031 is designed to build muscle and increase muscle strength by inhibiting molecules that bind to and signal through the cell surface ActRIIB receptor. ACE-031 is a recombinant fusion protein comprising a portion of the human ActRIIB receptor with a human antibody. Acceleron claims the resulting molecule is a freely circulating, decoy version of ActRIIB that removes proteins such as GDF-8 (myostatin) and other related molecules involved in limiting the growth and strength of muscle. The firm says early clinical studies have shown that a single high dose of ACE-031 resulted in participants developing about 1 kg of muscle within two weeks.
Acceleron is focused on developing biologics that modulate the growth of bone, muscle, fat, and the vasculature for the treatment of relevant diseases. The firm’s strategy is to develop antagonists of the relevant proteins within the growth and differentiation factor protein superfamily, which controls the growth and repair of a range of body tissues.
Acceleron’s clinical pipeline includes ACE-011, a fully human, soluble fusion protein derived from the extracellular domain of ActRIIA. In development in collaboration with Celgene, ACE-011 is currently undergoing Phase II trials for the treatment of chemotherapy-induced anemia. Acceleron claims Phase I studies involving healthy post-menopausal women have also shown that as well as boosting hemoglobin and red blood cell levels, ACE-011 therapy results in increased bone formation biomarkers, and significantly increased total hip bone mineral density. The firm claims the candidate could potentially be used to treat multiple facets of cancer, including anemia caused by chemotherapy, malignant bone disease, and the underlying tumor itself.