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Oral PCSK9 Inhibitor Developed Using mRNA Technology

Using novel mRNA display screening technology, researchers developed MK-0616, an oral PCSK9 inhibitor that “has the potential to be a highly effective cholesterol lowering therapy for patients in need … allowing more patients to achieve LDL-C goals and reduce cardiovascular risk earlier in their treatment journey.”

In addition to novel mRNA display screening technology, structure-based drug design enabled by novel synthetic chemistry was used to identify an agent “with exquisite potency and selectivity for PCSK9,” write the authors. In a single rising-dose phase 1 clinical trial, MK-0616 was administered once daily for 14 days, with these results: “MK-0616 displayed high affinity (Ki = 5pM) for PCSK9 in vitro and sufficient safety and oral bioavailability preclinically to enable advancement into the clinic. In Phase 1 clinical studies in healthy adults, single oral doses of MK-0616 were associated with >93% geometric mean reduction (95% CI, 84–103) of free, unbound plasma PCSK9; in participants on statin therapy, multiple–oral-dose regimens provided a maximum 61% geometric mean reduction (95% CI, 43–85) in low density lipoprotein cholesterol from baseline after 14 days of once-daily dosing of 20 mg MK-0616.”

Source: Circulation