Lerodalcibep-Liga

1 INDICATIONS AND USAGE LEROCHOL TM is indicated as an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH). LEROCHOL is a proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor indicated as an adjunct to diet and exercise: to reduce low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH). ( 1 )

2 DOSAGE AND ADMINISTRATION The recommended dosage of LEROCHOL is 300 mg administered subcutaneously once monthly. ( 2.1 ) Inject LEROCHOL subcutaneously into the abdomen or thigh. A caregiver or healthcare professional can administer into the upper arm. ( 2.2 ) Refer to the Instructions for Use for administration of prefilled syringe. ( 2.2 ) 2.1 Recommended Dosage The recommended dosage of LEROCHOL is 300 mg once monthly administered subcutaneously. Assess LDL-C when clinically indicated. The LDL-lowering effect of LEROCHOL may be measured as early as 4 weeks after initiation and, provided monthly dosing is continued, anytime thereafter without regard to timing of the dose. 2.2 Recommendations Regarding Missed Dose(s) If a dose is missed by: Less than 7 days, instruct the patient to administer LEROCHOL as soon as possible and resume the patient's original monthly dosage schedule. Seven (7) or more days, instruct the patient to administer LEROCHOL as soon as possible and start a new monthly dosage schedule based on this date. 2.3 Important Administration Instructions Train patients and/or their caregivers on how to prepare and administer LEROCHOL, according to the Instructions for Use, and instruct them to read and follow the Instructions for Use each time they use LEROCHOL. Prior to use, allow LEROCHOL to warm to room temperature up to 25°C (77°F) for at least 30 minutes if LEROCHOL has been refrigerated [see How Supplied/Storage and Handling ( 16 )] . Visually inspect LEROCHOL prior to administration. LEROCHOL is a clear to slightly opalescent, brownish-yellow to amber solution. Do not use if the solution is cloudy or contains particles. Inject LEROCHOL subcutaneously into the abdomen or the upper front thighs. If injected by a healthcare professional or caregiver, the back of the upper arms can also be a site of injection [see Instructions for Use] . Do not inject in an area of the skin that is tender, bruised, red, or indurated. Rotate injection sites for each administration. To administer the full 300 mg dose, push plunger down until the syringe is empty before removing from the injection site.

6 ADVERSE REACTIONS Common adverse reactions occurring in ≥1% of patients treated with LEROCHOL were injection site reactions, nasopharyngitis, diarrhea, nausea and peripheral edema. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact LIB Therapeutics, Inc. at 1-877-2-LEROCHOL 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 Primary Hypercholesterolemia Adverse Reactions in Two Pooled 52-week Controlled Trials In two pooled 52-week, double-blind, randomized, placebo-controlled trials (Trials 1 and 2), 1,229 patients received 300 mg of LEROCHOL subcutaneously every 4 weeks [see Clinical Studies ( 14 )] . The mean age was 64 years (range 25 to 90 years), 52% were 65 years of age or older, 37% female, 79% White, 18% Black or African American, 4% Asian; 7% identified as Hispanic or Latino ethnicity. At baseline, 9% of patients had a diagnosis of HeFH, 74% had established atherosclerotic cardiovascular disease (ASCVD), and 26% were at increased risk for ASCVD. Adverse reactions reported in at least 2% of LEROCHOL-treated patients and more frequently than in placebo-treated patients are shown in Table 1 . Adverse reactions led to treatment discontinuation in 4% of LEROCHOL-treated patients and placebo-treated patients. The most frequent adverse reaction leading to treatment discontinuation was injection site reactions, with a higher frequency in the LEROCHOL-treated group compared to placebo-treated patients (1% vs. 0%). Table 1: Adverse Reactions Occurring in ≥2% of LEROCHOL-treated Patients with Hypercholesterolemia and > 1% More Frequently than Placebo-treated Patients in Two Pooled 52-Week Trials (Trials 1 and 2) a Grouped terms composed of several similar terms Adverse Reaction a LEROCHOL 300 mg (N=1,229) % Placebo (N=612) % Nasopharyngitis 15 14 Injection site reactions 12 5 Peripheral edema 2 <1 Adverse Reactions in a 24-Week Controlled Trial In a 24-week, double-blind, randomized, placebo-controlled trial (Trial 3), 318 patients with HeFH received 300 mg of LEROCHOL subcutaneously every 4 weeks [see Clinical Studies ( 14 )]. Adverse reactions reported in at least 2% of LEROCHOL-treated patients, and more frequently than in placebo-treated patients are shown in Table 2 . Table 2: Adverse Reactions Occurring in ≥2% LEROCHOL-treated Patients with HeFH and >1% More Frequently than Placebo-treated Patients at 24 Weeks (Trial 3) Adverse Reaction LEROCHOL 300 mg (N=318) % Placebo (N=159) % a Grouped terms composed of several similar terms Injection site reactions a 18 3 Nasopharyngitis a 13 9 Diarrhea 3 1 Nausea 2 0 Peripheral edema a 2 <1

12.3 Pharmacokinetics Following a single subcutaneous administration, exposure to lerodalcibep-liga increased in a dose proportional manner over the dose range 75 to 300 mg of lerodalcibep-liga. Lerodalcibep-liga pharmacokinetics were observed at steady state in patients at the approved recommended dosage and are presented as mean (SD), unless otherwise specified. Lerodalcibep-liga maximum concentration (Cmax) is 31.4 (10.2) mcg/mL, and total systemic exposure (AUC0-tau) is 12,600 (5,190) (hrs*mcg/mL) following subcutaneous dose of lerodalcibep-liga 300 mg once every four weeks. Lerodalcibep-liga steady-state is reached following 2 to 3 doses. Lerodalcibep-liga accumulation is approximately 30% at the approved recommended dosage. Absorption The median (min, max) estimated subcutaneous bioavailability of lerodalcibep-liga is 83% (66%, 89%). The median (min, max) time to maximum plasma concentration (Tmax) is 6 days (2, 9 days) at steady state. Distribution Lerodalcibep-liga does not extensively distribute into tissues; the apparent volume of distribution is 5.3 L. Elimination As a protein, lerodalcibep-liga is expected to degrade to small peptides and amino acids. Clearance of free lerodalcibep-liga (CV%) is 0.36 L/day (30%) with an estimated half-life of approximately 10 days. The estimated elimination rate of lerodalcibep-liga (CV%) bound to PCSK9 is 0.47 L/day (22%) which corresponds to a half-life of approximately 1.5 days. Specific Populations No clinically significant differences in the pharmacokinetics of LEROCHOL were observed based on age (21 to 78 years), body weight, sex, race, mild (eGFR 60 to 89 mL/min) or moderate (eGFR 30 to 59 mL/min) renal impairment, or mild (total bilirubin 1.0 to 1.5 upper limit of normal or aspartate aminotransaminase greater than the upper limit of normal) or moderate (total bilirubin 1.5 to 3.0 upper limit of normal) hepatic impairment. The effect of severe renal impairment (eGFR less than 30 mL/min) or severe hepatic impairment on LEROCHOL pharmacokinetics is unknown. Drug Interaction Studies No formal clinical drug interaction studies have been performed.