LEROCHOL- lerodalcibep-liga injection, solution
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anum Ijaz M.B.B.S., M.D.[2]
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Overview
LEROCHOL- lerodalcibep-liga injection, solution is a proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor that is FDA approved for the treatment of low-density lipoprotein cholesterol (LDL-C)(reduction) in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH), as an adjunct to diet and exercise.. Common adverse reactions include injection site reactions, nasopharyngitis, diarrhea, nausea and peripheral edema..
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Hypercholesterolemia, Including Heterozygous Familial Hypercholesterolemia
- LEROCHOL 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).
Dosing Information
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.
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.
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.
- 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. 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.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of LEROCHOL- lerodalcibep-liga injection, solution in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of LEROCHOL- lerodalcibep-liga injection, solution in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding LEROCHOL- lerodalcibep-liga injection, solution FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of LEROCHOL- lerodalcibep-liga injection, solution in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of LEROCHOL- lerodalcibep-liga injection, solution in pediatric patients.
Contraindications
None.
Warnings
There is limited information regarding LEROCHOL- lerodalcibep-liga injection, solution Warnings' in the drug label.
Adverse Reactions
Clinical Trials Experience
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.
- 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%).
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)
| Adverse Reaction | LEROCHOL 300 mg (N=1,229) % | Placebo (N=612) % |
|---|---|---|
| Nasopharyngitis | 15 | 14 |
| Injection site reactionsa | 12 | 5 |
| Peripheral edema | 2 | <1 |
a Grouped terms composed of several similar terms
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.
- Adverse reactions reported in at least 2% of LEROCHOL-treated patients, and more frequently than in placebo-treated patients are shown in 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) % |
|---|---|---|
| Injection site reactionsa | 18 | 3 |
| Nasopharyngitis | 13 | 9 |
| Diarrhea | 3 | 1 |
| Nausea | 2 | 0 |
| Peripheral edema | 2 | <1 |
a Grouped terms composed of several similar terms
Postmarketing Experience
There is limited information regarding LEROCHOL- lerodalcibep-liga injection, solution Postmarketing Experience in the drug label.
Drug Interactions
There is limited information regarding LEROCHOL- lerodalcibep-liga injection, solution Drug Interactions in the drug label.
Use in Specific Populations
Pregnancy
Risk Summary
- Discontinue LEROCHOL when pregnancy is recognized.
- Alternatively, consider the ongoing therapeutic needs of the individual patient.
- LEROCHOL increases LDL-C uptake and lowers LDL-C levels in the circulation, thus decreasing cholesterol and possibly other biologically active substances derived from cholesterol; therefore, LEROCHOL may cause fetal harm when administered to pregnant patients based on the mechanism of action.
- In addition, treatment of hypercholesterolemia is not generally necessary during pregnancy.
- Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hypercholesterolemia for most patients.
- Available data from clinical trials on LEROCHOL use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes.
- In animal reproduction studies, there were no adverse developmental effects observed when pregnant monkeys were administered lerodalcibep-liga subcutaneously during organogenesis and through to parturition at doses up to 100 mg/kg/week [up to 119-fold the exposure at the maximum recommended human dose (MRHD) of 300 mg every month].
- The background risk of major birth defects and miscarriage for the indicated population is unknown.
- In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data
Animal Data
- In cynomolgus monkeys, no effects on embryo-fetal or postnatal development (up to 6 months of age) were observed when lerodalcibep-liga was dosed during organogenesis and through parturition at 30 and 100 mg/kg subcutaneously once weekly (exposures up to 119-fold the MRHD by AUC).
- An assessment of immune function in the infants showed no treatment-related adverse effects.
- Measurable lerodalcibep-liga serum concentrations were observed in the infant monkeys with infant serum concentrations approximately 2 to 7% of maternal serum concentrations on postnatal days 14, 21 and 28, indicating that lerodalcibep-liga has the potential to be transmitted from the mother to the developing fetus.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of LEROCHOL- lerodalcibep-liga injection, solution in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of LEROCHOL- lerodalcibep-liga injection, solution during labor and delivery.
Nursing Mothers
Risk Summary
- There are no data on the presence of lerodalcebip-liga in human milk, the effects on the breastfed infant, or the effects on milk production.
- In animal reproduction studies, lerodalcibep-liga was present in the milk of lactating monkeys.
- When a drug is present in animal milk, it is likely that the drug will be present in human milk.
- The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for LEROCHOL and any potential adverse effects on the breastfed infant from LEROCHOL or from the underlying maternal condition.
Data
- Low concentrations of lerodalcibep-liga were measured in milk samples collected from monkeys on post-partum day (PPD) 7 and PPD 14, when lerodalcibep-liga was dosed during organogenesis through parturition at 30 and 100 mg/kg subcutaneously once weekly (exposures up to 119-fold the MRHD by AUC).
- There is no information regarding whether lerodalcibep-liga ingested with milk transfers to neonatal or infant monkey circulation.
Pediatric Use
- The safety and effectiveness of LEROCHOL in pediatric patients have not been established.
- Clinical trials of LEROCHOL in pediatric patients with HeFH have not been conducted.
- Effectiveness of LEROCHOL was not demonstrated in a 24-week, randomized, open-label, active-controlled trial (NCT04034485) in 19 pediatric patients aged 10 to 17 years with homozygous familial hypercholesterolemia (HoFH).
Geriatic Use
There is no FDA guidance on the use of LEROCHOL- lerodalcibep-liga injection, solution in geriatric settings.
Gender
There is no FDA guidance on the use of LEROCHOL- lerodalcibep-liga injection, solution with respect to specific gender populations.
Race
There is no FDA guidance on the use of LEROCHOL- lerodalcibep-liga injection, solution with respect to specific racial populations.
Renal Impairment
- No dose adjustment is necessary in patients with mild to moderate renal impairment [estimated glomerular filtration rate (eGFR) ≥30 to <90 mL/min].
- LEROCHOL has not been studied in patients with severe renal impairment (eGFR < 30 mL/min) or end-stage renal disease.
Hepatic Impairment
- No dose adjustment is necessary in patients with mild (total bilirubin 1.0 to 1.5 upper limit of normal or aspartate aminotransaminase > upper limit of normal) or moderate (total bilirubin 1.5 to 3.0 upper limit of normal) hepatic impairment.
- LEROCHOL has not been studied in patients with severe hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of LEROCHOL- lerodalcibep-liga injection, solution in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of LEROCHOL- lerodalcibep-liga injection, solution in patients who are immunocompromised.
Administration and Monitoring
Administration
- The recommended dosage of LEROCHOL is 300 mg once monthly administered subcutaneously.
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.
- 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. 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.
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.
Monitoring
Recommended Dosage
- 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.
IV Compatibility
There is limited information regarding the compatibility of LEROCHOL- lerodalcibep-liga injection, solution and IV administrations.
Overdosage
There is limited information regarding LEROCHOL- lerodalcibep-liga injection, solution overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding LEROCHOL- lerodalcibep-liga injection, solution Pharmacology in the drug label.
Mechanism of Action
- Lerodalcibep-liga is a recombinant fusion protein that binds PCSK9 with picomolar affinity.
- PCSK9 binds to low-density lipoprotein receptor (LDLR) on the surface of hepatocytes to promote LDLR degradation within the liver.
- By inhibiting the binding of PCSK9 to LDLR, lerodalcibep-liga increases the number of LDLRs available to clear LDL-C from the blood.
Structure
- Lerodalcibep-liga is a recombinant fusion protein therapeutic agent comprised of a proprotein convertase subtilisin/kexin type 9 (PCSK9)-binding domain and human serum albumin (HSA).
- Lerodalcibep-liga is produced in genetically engineered mammalian (Chinese hamster ovary) cells as a single protein with an approximate molecular weight of 77 kDa.
- LEROCHOL (lerodalcibep-liga) injection is a clear to slightly opalescent, brownish-yellow to amber, sterile, preservative-free solution for subcutaneous injection.
- Each single-dose prefilled syringe contains 1.2 mL of lerodalcibep-liga (300 mg), histidine (3.07 mg), L-histidine monohydrochloride (0.88), polysorbate 80 (0.24 mg), sodium chloride (10.52), and Water for Injection.
Add structure
Dosage Forms and Strengths
- Injection: 300 mg/1.2 mL (250 mg/mL) of clear to slightly opalescent, brownish-yellow to amber solution in a single-dose prefilled syringe.
Pharmacodynamics
- After subcutaneous administration of 300 mg lerodalcibep-liga every month, greater than 90% suppression of PCSK9 occurs within 24 hours after dosing and is maintained throughout the dosing interval.
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.
Metabolism
- As a protein, lerodalcibep-liga is expected to degrade to small peptides and amino acids.
Elimination
- 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.
Immunogenicity
- The observed incidence of anti-drug antibodies (ADA) is highly dependent on the sensitivity and specificity of the assay.
- Differences in assay methods preclude meaningful comparisons of the incidence of ADA in the studies described below with the incidence of ADA in other studies, including those of lerodalcibep-liga or of other lerodalcibep products.
- During the 52-week treatment period in Trial 1 and Trial 2, 15.1% of LEROCHOL-treated patients were ADA positive, of whom 22.8% had neutralizing antibodies.
- There was no identified clinically significant effect of ADA and NAb on the pharmacokinetics, pharmacodynamics (free PCSK9), safety, or effectiveness (LDL-C) of LEROCHOL over the treatment period of 52 weeks.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment of Fertility
- Carcinogenicity studies have not been performed with lerodalcibep-liga.
- The mutagenic potential of lerodalcibep-liga has not been evaluated; however, proteins are not expected to directly interact with DNA or chromosomes.
- Fertility studies were not performed.
- However, in a chronic 6-month toxicology study in sexually mature cynomolgus monkeys, no adverse lerodalcibep-liga-related effects on surrogate markers of fertility (reproductive organ histopathology, menstrual cycling, or sperm parameters) were observed when lerodalcibep-liga was administered subcutaneously at 30 and 100 mg/kg once weekly.
Clinical Studies
- The efficacy of LEROCHOL was evaluated in three randomized, double-blind, placebo-controlled trials that enrolled 2,017 adults with HeFH, clinical ASCVD, or increased risk for ASCVD, who were on a stable low-fat, low-cholesterol diet and maximally tolerated statin therapy and who required additional LDL-C lowering.
Primary Hypercholesterolemia
- Trial 1 (NCT04797247) and Trial 2 (NCT04806893) were both multicenter, double-blind, randomized, placebo-controlled 52-week trials in which 1,844 adults with ASCVD or at increased risk for ASCVD events were randomized 2:1 to receive subcutaneous injections of either LEROCHOL 300 mg (n=1,229) or placebo (n=615) every 4 weeks.
- Patients were stable on a low-fat, low-cholesterol diet, maximally tolerated dose of statin with or without other oral lipid modifying therapy, and required additional LDL-C reduction.
Baseline Disease and Demographic Characteristics
- The mean age in Trial 1 at baseline was 64 years (range: 25 to 90 years), 49% were 65 years or older, 30% were female, 80% were White, 17% were Black or African American, and 3% were Asian; 1.1% identified as Hispanic or Latino ethnicity.
- Thirty four percent (34%) of patients had diabetes at baseline, 86% established ASCVD, and 14% at increased risk for CVD events.
- The mean baseline LDL-C was 102 mg/dL.
- At the time of randomization, 87% of patients were receiving statin therapy and of these 53% were receiving high-intensity statin therapy; 18% were receiving ezetimibe either in combination with a statin or alone.
- The mean age in Trial 2 at baseline was 65 years (range: 27 to 87 years), 54% were 65 years or older, 45% were female, 78% were White, 18% were Black or African American, and 4% were Asian; 13% identified as Hispanic or Latino ethnicity.
- Forty-three percent (43%) of patients had diabetes at baseline, 48% established ASCVD, and 52% at increased risk for CVD events.
- The mean baseline LDL-C was 116 mg/dL.
- At the time of randomization, 83% of patients were receiving statin therapy and of these, 39% were on high-intensity doses; 17% were receiving ezetimibe either in combination with a statin or alone.
Endpoint Results
- The primary efficacy outcome measure in Trial 1 was the placebo adjusted intent to treat (ITT) analysis of percent change in LDL-C from baseline to Week 52.
- The difference between the LEROCHOL and placebo group in mean percentage change in LDL-C from baseline to Week 52 was -55% (95% CI: -59.2%, -50.8%; p < 0.0001).
Changes in Lipid Parameters in Patients with Hypercholesterolemia and ASCVD or Increased Risk for ASCVD Events on Maximally Tolerated Statin Therapy (Percent Change from Baseline to Week 52 in Trial 1)
| Treatment Group | LDL-C | Total Cholesterol | Non-HDL-C | ApoB |
|---|---|---|---|---|
| Placebo (n = 308) | -0.1 | -0.2 | -0.7 | +1 |
| LEROCHOL 300mg (n = 614) | -55 | -31 | -46 | -39 |
| Difference from placebo (LS Mean) (95% CI) | -55 (-59, -51) | -31 (-33, -28) | -45 (-48, -41) | -40 (-44, -37) |
LDL-C, Total Cholesterol, non-HDL-C and ApoB at Week 52 were missing for 7.5% and 10.4% of patients assigned to placebo and LEROCHOL, respectively. Multiple imputation washout model was implemented for imputing missing values at Week 52. Least-squares mean from an Analysis of Covariance (ANCOVA) model including treatment as a factor and baseline value as a covariate, assuming unequal variances between groups. p-value <0.001 for superiority, controlled for Type I error rate. Not controlled for Type I error rate.
Figure 1: Mean Percent Change from Baseline in LDL-C Over 52 Weeks in Patients with Hypercholesterolemia and ASCVD or Increased Risk for ASCVD Events on Maximally Tolerated Statin Therapy (Trial 1)
- The primary efficacy outcome measure in Trial 2 was the percent change in LDL-C from baseline compared to placebo to Week 52.
- The difference between the LEROCHOL and placebo groups by ITT analysis in mean percentage change in LDL-C from baseline to Week 52 was -50% (95% CI: -54.2%, -45.2%; p < 0.0001).
Changes in Lipid Parameters in Patients with Hypercholesterolemia and ASCVD or Increased Risk for ASCVD Events on Maximally Tolerated Statin Therapy (Percent Change from Baseline to Week 52 in Trial 2)
| Treatment Group | LDL-C | Total Cholesterol | Non-HDL-C | ApoB |
|---|---|---|---|---|
| Placebo (n = 307) | +0.3 | +1 | +1 | +2 |
| LEROCHOL 300mg (n = 615) | -49 | -28 | -41 | -36 |
| Difference from placebo (LS Mean) (95% CI) | -50 (-54, -45) | -29 (-32, -26) | -42 (-46, -38) | -38 (-42, -35) |
LDL-C and non-HDL-C at Week 52 were missing for 10.7% and 11.2% of patients assigned to placebo and LEROCHOL, respectively. Total Cholesterol and ApoB at Week 52 were missing for 10.4% and 11.2% of patients assigned to placebo and LEROCHOL, respectively. Multiple imputation washout model was implemented for imputing missing values at Week 52. Least-squares mean from an Analysis of Covariance (ANCOVA) model including treatment and CVD status as factors and baseline value as a covariate, assuming unequal variances between groups. p-value <0.001 for superiority, controlled for Type I error rate. Not controlled for Type I error rate.
Figure 2: Mean Percent Change from Baseline in LDL-C Over 52 Weeks in Patients with Hypercholesterolemia and ASCVD or Increased Risk for ASCVD Events on Maximally Tolerated Statin Therapy (Trial 2)
Heterozygous Familial Hypercholesterolemia in Adults
- Trial 3 (NCT04797104) was a multicenter, double-blind, randomized, placebo-controlled 24-week trial in which 478 patients with HeFH were randomized 2:1 to receive subcutaneous injections of either LEROCHOL 300 mg (n = 319) or placebo (n = 159) every 4 weeks.
- Patients were stable on diet, maximally tolerated dose of statin, with or without other oral lipid modifying therapy, and required additional LDL-C reduction.
Baseline Disease and Demographic Characteristics
- The mean age at baseline was 53 years (range: 18 to 80 years), 19% were aged 65 years or older, 52% were female, 87% were White, 8% were Black or African American, and 5% were Asian; 1% identified as Hispanic or Latino ethnicity.
- Forty-five percent of patients had diabetes at baseline.
- The mean baseline LDL-C was 150 mg/dL.
- At the time of randomization, 89% of patients were receiving statin therapy with 67% receiving high-intensity doses, and 49% also on ezetimibe.
Endpoint Results
- The primary efficacy outcome measure in Trial 3 was the percent change in LDL-C from baseline to Week 24.
- The difference between the LEROCHOL and placebo groups in mean percentage change in LDL-C from baseline to Week 24 was -59% (95% CI: -65.7%, -51.7%; p < 0.0001).
Changes in Lipid Parameters in Patients with HeFH, on Maximally Tolerated Statin Therapy (Percent Change from Baseline to Week 24 in Trial 3)
| Treatment Group | LDL-C | Total Cholesterol | Non-HDL-C | ApoB |
|---|---|---|---|---|
| Placebo (n = 159) | + 8 | +5 | +7 | +7 |
| LEROCHOL 300mg (n = 319) | -51 | -32 | -44 | -37 |
| Difference from placebo (LS Mean) (95% CI) | -59 (-66, -52) | -37 (-41, -32) | -51 (-57, -45) | -44 (-49, -39) |
LDL-C, Total Cholesterol and non-HDL-C at Week 24 were missing for 3.1% and 2.8% of patients assigned to placebo and LEROCHOL, respectively. ApoB at Week 24 was missing for 3.1% and 3.1% of patients assigned to placebo and LEROCHOL, respectively. Multiple imputation washout model was implemented for imputing missing values at Week 24. Least-squares mean from an Analysis of Covariance (ANCOVA) model including treatment and CVD status as factors and baseline value as a covariate, assuming unequal variances between groups. p-value <0.001 for superiority, controlled for Type I error rate. Not controlled for Type I error rate.
Figure 3: Mean Percent Change from Baseline in LDL-C Over 24 Weeks in Patients with HeFH on Maximally Tolerated Statin Therapy (Trial 3)
How Supplied
- LEROCHOL (lerodalcibep-liga) injection 300 mg/1.2 mL (250 mg/mL) is supplied as a single-dose prefilled syringe for subcutaneous injection and is a clear to slightly opalescent, brownish-yellow to amber, sterile, preservative-free solution.
- LEROCHOL is supplied in cartons containing one single-dose prefilled syringe (NDC 84685-300-01).
Storage
- Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light.
- Do not freeze.
- Do not shake.
- If needed, LEROCHOL may be kept at room temperature up to 25°C (77°F) in the original carton and must be used within 3 months of being removed from the refrigerator.
- If not used within 3 months, discard LEROCHOL.
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Patient Counseling Information
- Advise the patient and/or caregiver to read the FDA-Approved Patient Labeling (Patient Information and Instructions for Use).
- Provide guidance to patients and caregivers on proper subcutaneous injection technique and how to use the prefilled syringe correctly.
- Inform patients that the prefilled syringe should be allowed to warm to room temperature for 30 minutes prior to use, if refrigerated.
Precautions with Alcohol
Alcohol-LEROCHOL- lerodalcibep-liga injection, solution interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
Look-Alike Drug Names
There is limited information regarding LEROCHOL- lerodalcibep-liga injection, solution Look-Alike Drug Names in the drug label.
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References
The contents of this FDA label are provided by the National Library of Medicine.