The FDA approved subcutaneous inclisiran (Leqvio) to be used alongside diet and maximally tolerated statin therapy in adult patients with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (ASCVD) who need to reduce their levels of low-density lipoprotein cholesterol (LDL-C).
This approval was based on findings from a trio of randomized, double-blind, placebo-controlled clinical trials that pitted inclisiran injections against placebo among a total of 3,457 adults with either HeFH or clinical ASCVD who were taking maximally tolerated statin therapy but required additional LDL-C lowering.
In all three studies, the primary outcome was percent change in LDL-C from study initiation to day 510; patients received subcutaneous injections of either 284 mg inclisiran or placebo on four study days—day 1, day 90, day 270, and day 450.
“Study 1 [ORION-10] enrolled 1,561 adults with ASCVD,” the FDA explained. “At day 510, the [inclisiran] group had an average LDL-C decrease of 51% whereas the placebo group had an average LDL-C increase of 1%. Study 2 [ORION-11] enrolled 1,414 adults with ASCVD. At day 510, the [inclisiran] group had an average LDL-C decrease of 46% whereas the placebo group had an average LDL-C increase of 4%. Study 3 [ORION-9] enrolled 482 adults with HeFH. At day 510, the [inclisiran] group had an average LDL-C decrease of 40% whereas the placebo group had an average LDL-C increase of 8%.”
The approved dosage for subcutaneous inclisiran is 284 mg administered as a single injection at treatment initiation, again at three months, and then every six months.
The FDA noted that the effect of inclisiran on cardiovascular morbidity and mortality has not been determined. Common adverse events associated with the drug included injection site reaction, joint stiffness, urinary tract infection, diarrhea, bronchitis, pain in extremities, and difficulty breathing.
Inclisiran is manufactured by Novartis.
John McKenna, Associate Editor, BreakingMED™
Cat ID: 308
Topic ID: 74,308,730,308,914,192,725,925
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