Under this exclusive global development andcommercialization alliance, Alnylam would also be eligible to receive scaleddouble-digit royalties on global products sales of ALN-PCS products.
"This new alliance unites two organizations with ashared culture and commitment to innovation. In my view and past experience,there could be no stronger partner for our ALN-PCS program than The MedicinesCompany, which has demonstrated industry-wide leadership in the advancement ofcardiovascular medicines to patients and remarkable success in its strategy ofin-licensing, developing, and commercializing breakthrough products," said Dr. JohnMaraganore, CEO of Alnylam. "For Alnylam, this new partnership enables theadvancement of ALN-PCS, an important program within our 'Alnylam 5x15' productdevelopment and commercialization strategy focused on RNAi therapeuticsdirected toward genetically validated targets. We believe that the ALN-PCSprogram holds great promise for the development of a significant therapeuticoption for patients with hypercholesterolemia, and that the unique mechanism ofaction for ALN-PCS could provide a differentiated and potentially best-in-classstrategy for PCSK9 antagonism."
PCSK9 (proprotein convertase subtilisin/kexin type9) is a protein that regulates low-density lipoprotein (LDL) receptor levels onhepatocytes; gain-of-function human mutations in PCSK9 are associated withhypercholesterolemia while loss-of-function mutations are associated with lowerlevels of LDL cholesterol and a reduced risk of cardiovascular disease. ALN-PCSis a PCSK9 synthesis inhibitor that reduces intracellular and extracellularlevels of PCSK9 resulting in lowered plasma levels of LDL-C. Also of interestin this collaboration is MDCO-216, a naturally occurring variant of a proteinfound in high-density lipoprotein (HDL) that is a reverse cholesterol transportagent designed to reduce atherosclerotic plaque burden development and therebyreduce the risk of adverse thrombotic events.
"Our focuson acute and intensive care medicine has led us to a leadership position withAngiomax (bivalirudin) and potentially with cangrelor in the management ofpatients in extreme risk as a consequence of the rupture of their vulnerablecoronary artery plaque at and around the time of acute coronary syndromes," saidDr. Clive Meanwell, chairman and CEO of The Medicines Company. "Meantime, wehave made progress with MDCO-216 (ApoA-1 Milano), a turbocharged form of HDL-C whichhas the potential to modify disease through reverse cholesterol transport."
Meanwell finds the collaboration with Alnylam "exciting"because as a leader in their field of RNAi, the company "adds a secondpotentially disease modifying approach and more cutting edge technology to ourportfolio. We have seen that PCSK9 gene silencing can substantially reduceLDL-cholesterol in patients and has epidemiological and disease mechanismsstudies suggest this can further reduce the risks of the world's number onekiller, coronary artery disease. Clearly we see the complementarity ofapproaches which increase 'good cholesterol' and decrease 'bad cholesterol'. Welook forward to working with our colleagues at Alnylam for whom we have thegreatest respect and admiration based upon earlier collaborations particularlyaround Angiomax, which was invented by John Maraganore."
Under this alliance, The Medicines Company andAlnylam intend to collaborate on the advancement of the ALN-PCS program.Alnylam's ALN-PCS program includes ALN-PCS02, an intravenously administered RNAitherapeutic which has completed a Phase I trial, and ALN-PCSsc, asubcutaneously administered RNAi therapeutic currently in preclinicaldevelopment.
Alnylam will continue the program for an estimatedone to two years to complete certain pre-clinical and Phase I clinical studies.The Medicines Company is responsible for leading and funding development fromPhase II forward and commercializing the ALN-PCS program if successful.
As some market-watchers have noted, the move to team up with Alnylam to attack a relatively new and uncertain cholesterol target may have much to do with the fact The Medicines Company could face generic competition for Angiomax as early as 2015. The company has reached agreement with some companies to delay their entry into that market until 2019, but several other companies with designs on a generic version of Angiomax have yet to be convinced to do the same.