LEQVIO
Generic: INCLISIRAN
Basic Information
Manufacturer
Novartis Pharmaceuticals Corporation
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
SUBCUTANEOUS
FDA Set ID
6fc0afca-4513-4c35-b594-6544aee29a44
Indications & Usage
1 INDICATIONS AND USAGE LEQVIO ® is indicated as an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in: adults with hypercholesterolemia.
adults and pediatric patients aged 12 years and older with heterozygous familial hypercholesterolemia (HeFH).
pediatric patients aged 12 years and older with homozygous familial hypercholesterolemia (HoFH).
LEQVIO is a small interfering RNA (siRNA) directed to proprotein convertase subtilisin kexin type 9 (PCSK9) mRNA indicated as an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in: adults with hypercholesterolemia.
( 1 ) adults and pediatric patients aged 12 years and older with heterozygous familial hypercholesterolemia (HeFH).
( 1 ) pediatric patients aged 12 years and older with homozygous familial hypercholesterolemia (HoFH).
( 1 )
adults and pediatric patients aged 12 years and older with heterozygous familial hypercholesterolemia (HeFH).
pediatric patients aged 12 years and older with homozygous familial hypercholesterolemia (HoFH).
LEQVIO is a small interfering RNA (siRNA) directed to proprotein convertase subtilisin kexin type 9 (PCSK9) mRNA indicated as an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in: adults with hypercholesterolemia.
( 1 ) adults and pediatric patients aged 12 years and older with heterozygous familial hypercholesterolemia (HeFH).
( 1 ) pediatric patients aged 12 years and older with homozygous familial hypercholesterolemia (HoFH).
( 1 )
Adverse Reactions
6 ADVERSE REACTIONS The following adverse reactions are also discussed in other sections of the label: Hypersensitivity Reactions [see Warnings and Precautions (5.1)] Common adverse reactions in clinical trials (≥ 3%): injection site reaction, arthralgia, and bronchitis.
( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Adverse Reactions in Adults with Hypercholesterolemia The data in Table 1 are derived from 3 placebo-controlled trials that included 1,833 adults with hypercholesterolemia treated with LEQVIO, including 1,682 exposed for 18 months (median treatment duration of 77 weeks) [see Clinical Studies (14)] .
The mean age of the population was 64 years, 32% of the population were female, 92% were White, 6% were Black or African American, 1% were Asian, and < 1% were other races; 6% identified as Hispanic or Latino ethnicity.
At baseline, 12% of patients had a diagnosis of HeFH and 85% had clinical atherosclerotic cardiovascular disease (ASCVD).
Adverse reactions reported in at least 3% of LEQVIO-treated patients, and more frequently than in placebo-treated patients, are shown in Table 1.
Table 1: Adverse Reactions Occurring in Greater Than or Equal to 3% of LEQVIO-treated Adults with Hypercholesterolemia and More Frequently than with Placebo (Trials 1, 2, and 3) Adverse Reactions Placebo (N = 1,822) % LEQVIO (N = 1,833) % †includes related terms such as: injection site pain, erythema and rash Injection site reaction† 2 8 Arthralgia 4 5 Bronchitis 3 4 Adverse reactions led to discontinuation of treatment in 2.5% of patients treated with LEQVIO and 1.9% of patients treated with placebo.
The most common adverse reactions leading to treatment discontinuation in patients treated with LEQVIO were injection site reactions (0.2% versus 0% for LEQVIO and placebo, respectively).
Adverse Reactions in Pediatric Patients with HeFH In a 24-month, two-part trial of 141 pediatric patients aged 12 years and older with HeFH (Trial 4), consisting of a 12-month randomized, double-blind, placebo-controlled part (Part 1/Year 1), followed by a 12-month open-label part (Part 2/Year 2), 93 patients received 284 mg of LEQVIO subcutaneously during Part 1 and 139 patients were treated with LEQVIO during Part 2 [see Clinical Studies (14)] .
During Part 2, 91 patients continued LEQVIO treatment for a second year and 48 patients switched from placebo to LEQVIO for 1 year of treatment.
The safety profile reported in pediatric patients with HeFH was consistent with the description above for adult patients with hypercholesterolemia, with the exception of headache.
In pediatric patients with HeFH, the incidence of headache was 6% among patients who received placebo versus 13% of LEQVIO-treated patients during the double-blind study period.
Adverse Reactions in Pediatric Patients with HoFH In a 24-month, two-part trial of 13 pediatric patients aged 12 years and older with HoFH (Trial 5), consisting of a 12-month randomized, double-blind, placebo-controlled part (Part 1/Year 1), followed by a 12-month open-label part (Part 2/Year 2), 9 patients received 284 mg of LEQVIO administered subcutaneously during Part 1 and 13 patients were treated with LEQVIO during Part 2 [see Clinical Studies (14)] .
During Part 2, 9 patients continued LEQVIO treatment for a second year and 4 patients switched from placebo to LEQVIO for 1 year of treatment.
The safety profile reported in pediatric patients was consistent with adult patients with hypercholesterolemia.
6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of LEQVIO.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Hypersensitivity: anaphylaxis, angioedema, rash, pruritus, and urticaria.
( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Adverse Reactions in Adults with Hypercholesterolemia The data in Table 1 are derived from 3 placebo-controlled trials that included 1,833 adults with hypercholesterolemia treated with LEQVIO, including 1,682 exposed for 18 months (median treatment duration of 77 weeks) [see Clinical Studies (14)] .
The mean age of the population was 64 years, 32% of the population were female, 92% were White, 6% were Black or African American, 1% were Asian, and < 1% were other races; 6% identified as Hispanic or Latino ethnicity.
At baseline, 12% of patients had a diagnosis of HeFH and 85% had clinical atherosclerotic cardiovascular disease (ASCVD).
Adverse reactions reported in at least 3% of LEQVIO-treated patients, and more frequently than in placebo-treated patients, are shown in Table 1.
Table 1: Adverse Reactions Occurring in Greater Than or Equal to 3% of LEQVIO-treated Adults with Hypercholesterolemia and More Frequently than with Placebo (Trials 1, 2, and 3) Adverse Reactions Placebo (N = 1,822) % LEQVIO (N = 1,833) % †includes related terms such as: injection site pain, erythema and rash Injection site reaction† 2 8 Arthralgia 4 5 Bronchitis 3 4 Adverse reactions led to discontinuation of treatment in 2.5% of patients treated with LEQVIO and 1.9% of patients treated with placebo.
The most common adverse reactions leading to treatment discontinuation in patients treated with LEQVIO were injection site reactions (0.2% versus 0% for LEQVIO and placebo, respectively).
Adverse Reactions in Pediatric Patients with HeFH In a 24-month, two-part trial of 141 pediatric patients aged 12 years and older with HeFH (Trial 4), consisting of a 12-month randomized, double-blind, placebo-controlled part (Part 1/Year 1), followed by a 12-month open-label part (Part 2/Year 2), 93 patients received 284 mg of LEQVIO subcutaneously during Part 1 and 139 patients were treated with LEQVIO during Part 2 [see Clinical Studies (14)] .
During Part 2, 91 patients continued LEQVIO treatment for a second year and 48 patients switched from placebo to LEQVIO for 1 year of treatment.
The safety profile reported in pediatric patients with HeFH was consistent with the description above for adult patients with hypercholesterolemia, with the exception of headache.
In pediatric patients with HeFH, the incidence of headache was 6% among patients who received placebo versus 13% of LEQVIO-treated patients during the double-blind study period.
Adverse Reactions in Pediatric Patients with HoFH In a 24-month, two-part trial of 13 pediatric patients aged 12 years and older with HoFH (Trial 5), consisting of a 12-month randomized, double-blind, placebo-controlled part (Part 1/Year 1), followed by a 12-month open-label part (Part 2/Year 2), 9 patients received 284 mg of LEQVIO administered subcutaneously during Part 1 and 13 patients were treated with LEQVIO during Part 2 [see Clinical Studies (14)] .
During Part 2, 9 patients continued LEQVIO treatment for a second year and 4 patients switched from placebo to LEQVIO for 1 year of treatment.
The safety profile reported in pediatric patients was consistent with adult patients with hypercholesterolemia.
6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of LEQVIO.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Hypersensitivity: anaphylaxis, angioedema, rash, pruritus, and urticaria.