FDA Expands Label for Inclisiran to Include Adults With High LDL-C, Increased Risk of Heart Disease

The FDA has approved an expanded label for inclisiran (Leqvio; Novartis) for earlier use among individuals with elevated low-density lipoprotein cholesterol (LDL-C) who have an elevated risk of heart disease, as an adjunct to diet and a statin therapeutic regimen. The updated label includes patients with comorbidities, such as hypertension and diabetes, and who have yet to experience a cardiovascular event.

"High LDL-C is one of the most readily modifiable risk factors for heart disease and this label update for Leqvio will help us reach a greater number of patients who struggle with lowering their LDL-C,” said Victor Bulto, president of Novartis Innovative Medicines US, in a press release.

Inclisiran (Leqvio) is a small interfering ribonucleic acid (siRNA) that was initially approved by the FDA in December 2021 for patients who are on a maximally-tolerated dose of statins and need additional LDL-C reduction.

The expanded indication for primary hyperlipidemia will allow for greater use of inclisiran as an adjunct to diet and statin use beyond the previously approved indications for patients with atherosclerotic cardiovascular disease (ASCVD) and heterozygous familial hypercholesterolemia (HeFH).

Three double-blind, randomized, placebo-controlled clinical trials demonstrated inclisiran’s efficacy in 3457 patients with ASCVD or HeFH on maximally-tolerated statin therapy.

The researchers found that inclisiran reduced LDL-C by 48%-52%, total cholesterol by 30%-33%, non-HDL-C by 42%-47%, and apoprotein B by 36%-43% from baseline in these 3 studies.

Inclisiran is supplied in a single-dose prefilled syringe containing 1.5 ml of clear and colorless to pale-yellow solution at pH 7.0 with 284 mg of the drug. Health care professionals should store inclisiran between 20-25 degrees C (68-77 degrees F) and administer inclisiran to patients subcutaneously in the abdomen, upper arm, or thigh.

They should administer the second dose 3 months after the first dose and then 1 dose every 6 months. If the patient misses a dose, health care professionals must determine the time elapsed since the planned dose. If fewer than 3 months have elapsed, they should administer the dose and continue with the patient’s original schedule; otherwise, the patient must restart a new regimen.

Inclisiran, administered as 2 doses a year following 2 initial doses, has been shown to lower LDL-C by up to 52% compared with placebo among patients with heart disease or with an increased risk of heart disease who were unable to reach their LDL-C target on statin therapy.

The updated label also removes the Limitations of Use statement. The safety section was updated to remove 4 adverse events (AEs) because the frequency of these AEs were similar in the placebo arm.

The most common AEs experienced by patients on inclisiran are injection site reactions (pain, erythema, and rash). Other AEs reported with greater frequency than placebo during clinical trials were arthralgia, urinary tract infections, diarrhea, bronchitis, and dyspnea.

There are no contraindications to inclisiran. Dosage reductions are not required for patients with mild to moderate hepatic dysfunction, those with mild to severe renal dysfunction, or for geriatric patients. Inclisiran has not been studied in severe hepatic impairment. No drug interactions occur with inclisiran as it is metabolized by nucleases.

Health care professionals should avoid administering inclisiran in infected or injured areas of skin. They should discard inclisiran if they observe particulate matter or discoloration.

Reference

US FDA approves expanded indication for Novartis Leqvio® (inclisiran) to include treatment of adults with high LDL-C and who are at increased risk of heart disease. Novartis. News release. July 10, 2023. https://www.prnewswire.com/news-releases/us-fda-approves-expanded-indication-for-novartis-leqvio-inclisiran-to-include-treatment-of-adults-with-high-ldl-c-and-who-are-at-increased-risk-of-heart-disease-301872495.html?tc=eml_cleartime