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Merck & Co.’s PCSK9 inhibitor MK-0616 showcases the potential of macrocycles as oral drugs for extracellular targets, even as several companies explore intracellular and macrocycle–drug conjugate possibilities.
Merck & Co. has started phase III testing of its oral macrocyclic peptide inhibitor of PCSK9 for atherosclerotic cardiovascular disease, one of the biggest killers worldwide. If successful, the drug will have to play catch-up against much-heralded but, as yet, little-used injectable PCSK9-targeted therapeutics. An oral option could make all the difference, hopes Merck — while also renewing interest in the potential of macrocyclic agents.