Another Way to Target PCSK9?

This phase 1 study tantalizingly suggests that drugs targeting proprotein convertase subtilisin–kexin type 9 could be given infrequently, but the larger question of efficacy remains.

Proprotein convertase subtilisin–kexin type 9 (PCSK9) is attracting a lot of attention as a target for LDL cholesterol–lowering therapies. Ongoing trials will soon tell us whether there are benefits to the currently approved PCSK9-blocking antibody drugs, which must be administered biweekly or monthly. Small interfering RNA (siRNA) molecules are another approach that might allow administration at less-frequent intervals. This two-stage, manufacturer-sponsored, phase 1 trial examined the investigative drug inclisiran, a long-acting, subcutaneously delivered synthetic siRNA molecule directed against PCSK9. Study entry requirements included serum LDL cholesterol levels ≥100 mg/dL and fasting triglyceride levels <400 mg/dL.

In the first stage, a…

Reviewing Author

Harlan M. Krumholz, MD, SM

Disclosures

Consultant/Advisory BoardUnited Healthcare; Element Science; Eyedentifeye, F-Prime

EquityHugo Health; Refactor Health; Element Science

Grant/Research SupportPfizer; Agency for Healthcare Research and Quality; Janssen Research and Development, National Institute of Biomedical Imaging and Engineering; National Heart, Lung, and Blood Institute; Centers for Disease Control and Prevention; National Cancer Institute; American Heart Association

Harlan M. Krumholz, MD, SM

Disclosures

Consultant/Advisory BoardUnited Healthcare; Element Science; Eyedentifeye, F-Prime

EquityHugo Health; Refactor Health; Element Science

Another Way to Target PCSK9?

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Reviewing Author