FDA Approvals, Highlights, and Summaries: Cardiology 

February 17, 2022

Leqvio (inclisiran)

Inclisiran is a double-stranded small interfering ribonucleic acid (siRNA), conjugated on the sense strand with triantennary N-acetylgalactosamine (GalNAc) to facilitate uptake by hepatocytes. In hepatocytes, inclisiran utilizes the RNA interference mechanism and directs catalytic breakdown of mRNA for proprotein convertase subtilisin kexin type 9 (PCSK9). This increases low-density lipoprotein (LDL-C) receptor recycling and expression on the hepatocyte cell surface, which increases LDL-C uptake and lowers LDL-C levels in the circulation.

Inclisiran is indicated as an adjunct to diet and maximally tolerated statin therapy for adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (ASCVD) who require additional LDL-C lowering. The subcutaneous injection is administered on Day 1, at Day 90, and then every 6 months thereafter.

A total of 1561 and 1617 patients underwent randomization in the phase 3 ORION-10 and ORION-11 trials, respectively. At day 510, inclisiran (plus maximally tolerated statin therapy) reduced LDL cholesterol levels by 52.3% in the ORION-10 trial and by 49.9% in the ORION-11 trial (P< 0.001 for all comparisons vs. placebo). N Engl J Med. 2020 Apr 16;382(16):1507-1519

Evkeeza (evinacumab)

Evinacumab is a recombinant human monoclonal antibody that binds to and inhibits angiopoietin–like 3 (ANGPTL3). ANGPTL3 inhibits lipoprotein lipase and endothelial lipase, thereby reducing lipid metabolism. Evinacumab inhibits ANGPTL3 and results in increased lipid metabolism, leading to decreased low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. Evinacumab is indicated as an adjunct to other LDL-C–lowering therapies for homozygous familial hypercholesterolemia in adults and adolescents aged 12 years and older.

Approval was based on the phase 3 ELIPSE trial (n = 65). The study found that patients undergoing stable lipid-lowering treatment in whom an intravenous infusion of evinacumab was administered every 4 weeks achieved, by week 24, a 47.1% relative reduction in their LDL-C level, as compared to a 1.9% increase seen in patients treated with a placebo (P<.001). N Engl J Med . 2020;383:711-720

Verquvo (vericiguat)

Vericiguat stimulates soluble guanylate-cyclase (sGC), the intracellular receptor for endogenous nitric oxide (NO), which catalyzes cyclic guanosine monophosphate (cGMP) production; cGMP plays a role in the regulation of vascular tone, cardiac contractility, and cardiac remodeling. By directly stimulating sGC, independently of and synergistically with NO, vericiguat augments levels of intracellular cGMP, leading to smooth muscle relaxation and vasodilation. Vericiguat is indicated to reduce the risk of cardiovascular death and heart failure (HF) hospitalization, following hospitalization for HF or need for outpatient intravenous diuretics, in adults with symptomatic chronic HF and ejection fraction less than 45%.

Results from the phase 3 VICTORIA trial (n = 5050) showed that in patients with symptomatic chronic HF (New York Heart Association class II-IV) and left ventricular ejection fraction of less than 45%, vericiguat was superior to placebo in reducing the risk of cardiovascular death or heart failure hospitalization. These results were based on a time-to-event analysis (hazard ratio, 0.9; 95% confidence interval, 0.82-0.98; P=.02) and demonstrated an adverse event profile similar to placebo. N Engl J Med 2020; 382:1883-1893

Kerendia (finerenone)

Finerenone is indicated to reduce risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, nonfatal myocardial infarction, and hospitalization for heart failure in adults with chronic kidney disease (CKD) associated with type 2 diabetes mellitus. It is the first nonsteroidal mineralocorticoid receptor (MR) antagonist to be approved for this purpose.

Approval was based on the FIDELIO-DKD trial, a placebo-controlled study that involved over 5700 patients with type 2 diabetes mellitus to whom the maximum-tolerated dose of renin-angiotensin system inhibitor (RASI) was already being administered. However, until more data on finerenone is gathered, RASIs and SGLT-2 inhibitors will be the preferred agents for slowing chronic kidney disease in type 2 diabetes mellitus. N Engl J Med. 2020 Dec 3;383(23):2219-2229

Other cardiology approvals

Jardiance (empagliflozin) - Indicated to reduce the risk of cardiovascular death plus hospitalization for heart failure in adults with heart failure and reduced ejection fraction.

Xarelto (rivaroxaban) - Indicated, in combination with aspirin, to reduce risk of major thrombotic vascular events in patients with peripheral artery disease (PAD), including those who have recently undergone a lower extremity revascularization procedure due to symptomatic PAD.    

Praluent (alirocumab) - Indicated as an adjunct to other low-density lipoprotein cholesterol (LDL-C)–lowering therapies in adults with homozygous familial hypercholesterolemia to reduce LDL-C.

Entresto (sacubitril/valsartan) - Indication for heart failure expanded to include adults with preserved left ventricular ejection fraction.

Arcalyst (rilonacept) - Interleukin-1 inhibitor for treatment of recurrent pericarditis and to reduce risk of future recurrence in adults and children aged 12 years and older.

Roszet (rosuvastatin/ezetimibe) - New combination indicated to reduce low-density lipoprotein cholesterol in patients with primary nonfamilial hyperlipidemia or homozygous familial hypercholesterolemia.


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