The Medicines Company will develop and commercialize for Alnylam Pharmaceuticals a series of its RNA interference (RNAi) therapeutics targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) for treating excess cholesterol in the blood, in a collaboration that could net Alnylam as much as $205 million.
The collaboration will focus on drug candidates within Alnylam’s ALN-PCS program, includes a PCSK9 synthesis inhibitor that reduces intracellular and extracellular levels of the protein, resulting in lowered plasma levels of LDL-C or “bad” cholesterol.
The Medicines Company will pay Alnlyam $25 million cash up-front, and up to $180 million tied to undisclosed potential development and commercial milestones. Alnylam will also be eligible for scaled double-digit royalties on global products sales of ALN-PCS products.
Alnylam’s ALN-PCS program includes the intravenous RNAi therapeutic ALN-PCS02, which has completed a Phase I trial; and ALN-PCSsc, an injectable RNAi therapeutic now in preclinical development. Alnylam will continue the program for an estimated one to two years while the preclinical and Phase I clinical studies are being completed, with the Medicines Company leading and funding development from Phase II forward and commercializing the ALN-PCS program if successful.
PCSK9 proteins are the target of other drugs further along in development, including monoclonal antibody candidates from a Sanofi-Regeneron collaboration and from Amgen, the latter in Phase III trials.
“We believe that the ALN-PCS program holds great promise for the development of a significant therapeutic option for patients with hypercholesterolemia, and that the unique mechanism of action for ALN-PCS could provide a differentiated and potentially best-in-class strategy for PCSK9 antagonism,” John Maraganore, Ph.D., Alnylam’s CEO, said in a statement.
The Medicines Company says the collaboration will allow it to join Alnylam in advancing treatments complementary to Angiomax® (bivalirudin), a drug it licenses from Biogen Idec and which was developed by a team led by Dr. Maraganore before he joined Alnylam. Angiomax is an anticlotting medicine for patients whose coronary artery plaque has ruptured while their clogged arteries are being reopened through stents. The Medicines Company’s pipeline includes MDCO-216 (ApoA-1 Milano), a form of HDL-C with potential to lower cholesterol through reverse cholesterol transport.
ALN-PCS is part of Alnylam’s "5x15" product development and commercialization strategy focused on RNAi therapeutics.