Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Alirocumab and Cemiplimab
Alirocumab · 10 trials · 4 indications
The percent change in LDL-C from baseline to week 12 is defined as: 100x (LDL-C value at week 12 - LDL-C value at baseline) / LDL-C value at baseline.
Rate of apheresis treatments were normalized by the number of planned apheresis treatments according to each participant's established schedule at screening, week -10 to week -2. The normalized rate of apheresis was defined for each participant as the number of actual apheresis treatments received from week 7 to week 18 divided by the number of planned apheresis treatments per randomization strata at baseline (6 for Q2W and 12 for QW).
Adjusted LS means and standard errors at Week 24 and at averaged Week 21 to 24 from MMRM including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. ITT population (subjects without concomitant statin therapy): all randomized subjects who did not receive concomitant statin therapy, with one baseline and at least one post-baseline calculated LDL-C value on- or off-treatment. Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Adjusted least squares (LS) means and standard errors at Week 24 and at averaged Week 21 to 24 were obtained from a mixed effect model with repeated measures (MMRM) model to account for missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were used in this model (ITT analysis). ITT population (subjects with concomitant statin therapy): all randomized subjects who received concomitant statin therapy, with one baseline and at least one post-baseline calculated LDL-C value on- or off-treatment. Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Calculated LDL-C values were obtained from Friedewald formula. Adjusted Least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).
An AE was defined as any untoward medical occurrence in a participant administered a study drug which may or may not have a causal relationship with the study drug. Treatment- emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on- treatment period (time from the first dose of study drug to the last dose of study drug plus 70 days). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life- threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs.
By day 15, participants in groups A and C had received 1 subcutaneous (SC) dose of 150 mg alirocumab and participants in group B and D had received 1 SC dose of placebo. \[Baseline adjusted least squares (LS) means and standard errors were obtained using analysis of covariance (ANCOVA) model specifying the treatment arm as the fixed effect and the baseline measured LDL-C value as a covariate.\]
Calculated LDL-C values were obtained using the Friedewald formula. Baseline adjusted least squares (LS) means and standard errors were estimated using an analysis of covariance (ANCOVA) model including available post-baseline data on treatment from first investigational medicinal product (IMP) injection up to 21 days after last IMP injection (on-treatment analysis). Missing Week 12 data were imputed by last observation carried forward \[LOCF\] method.
Levels of bacterial endotoxin will be compared between study arms.
Levels of lipoteichoic acid will be compared between study arms.
| Arm | Type | Description |
|---|---|---|
| Alirocumab SC Q2W | EXPERIMENTAL | Alirocumab SC every 2 weeks (Q2W) from baseline (day 1) through week 10 during the double-blind treatment period Starting at week 12, and continuing through week 22, participants will receive open-label alirocumab SC Q2W |
| Placebo SC Q2W | EXPERIMENTAL | Matching placebo SC Q2W from baseline through week 10 during the double-blind treatment period Starting at week 12, and continuing through week 22, participants will receive open-label alirocumab SC Q2W |
| Placebo Q2W (Double Blind Period) | EXPERIMENTAL | Placebo (for alirocumab) subcutaneous (SC) injection Q2W up to Week 16. |
| Alirocumab 150 mg Q2W (Double Blind Period) | EXPERIMENTAL | Alirocumab 150 mg SC injection Q2W up to Week 16. |
| Alirocumab 150 Q2W (Open Label Treatment Period) | EXPERIMENTAL | Alirocumab 150 mg SC injection Q2W starting from Week 18 up to Week 76. |
| Placebo Q2W | PLACEBO_COMPARATOR | Two subcutaneous (SC) injections of placebo (for alirocumab) Q2W with or without stable statin therapy for 48 weeks. |
| Alirocumab 75 mg/ Up 150 mg Q2W | EXPERIMENTAL | One SC injection of each Alirocumab 75 mg and placebo Q2W with or without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk participants) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk participants) at Week 8. |
| Alirocumab 300 mg/ Up 150 mg Q4W | EXPERIMENTAL | Two SC injections of Alirocumab 150 mg Q4W alternating with two SC injections of placebo Q4W with or without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk participants) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk participants) at Week 8. |
| Rosuvastatin 20 mg | ACTIVE_COMPARATOR | Participants, who were receiving rosuvastatin 10 mg over-encapsulated tablet orally at baseline, received rosuvastatin 20 mg over-encapsulated tablet orally once daily (QD), placebo for alirocumab SC injection every two weeks (Q2W), and placebo for ezetimibe over-encapsulated tablet orally QD added to stable Lipid-Modifying Therapy (LMT) for 24 weeks. |
| Ezetimibe 10 mg + Rosuvastatin 10 mg | ACTIVE_COMPARATOR | Participants, who were receiving rosuvastatin 10 mg over-encapsulated tablet orally at baseline, received ezetimibe 10 mg over-encapsulated tablet orally QD, rosuvastatin 10 mg over-encapsulated tablet orally QD, and placebo for alirocumab SC injection Q2W added to stable LMT for 24 weeks. |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg | EXPERIMENTAL | Participants, who were receiving rosuvastatin 10 mg over-encapsulated tablet orally at baseline, received alirocumab 75 mg SC injection Q2W, rosuvastatin 10 mg over-encapsulated tablet orally QD, and placebo for ezetimibe over-encapsulated tablet orally QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history. |
| Rosuvastatin 40 mg | ACTIVE_COMPARATOR | Participants, who were receiving rosuvastatin 20 mg over-encapsulated tablet orally at baseline, received rosuvastatin 40 mg over-encapsulated tablet orally QD, placebo for alirocumab Q2W SC injection, and placebo for ezetimibe QD over-encapsulated tablet orally added to stable LMT for 24 weeks. |
| Ezetimibe 10 mg + Rosuvastatin 20 mg | ACTIVE_COMPARATOR | Participants, who were receiving rosuvastatin 20 mg over-encapsulated tablet orally at baseline, received ezetimibe 10 mg over-encapsulated tablet orally QD, rosuvastatin 20 mg over-encapsulated tablet orally QD, and placebo for alirocumab Q2W SC injection added to stable LMT for 24 weeks. |
| Alirocumab 75 mg/ up to 150 mg + Rosuvastatin 20 mg | EXPERIMENTAL | Participants, who were receiving rosuvastatin 20 mg over-encapsulated tablet orally at baseline, received alirocumab 75 mg Q2W SC injection, rosuvastatin 20 mg over-encapsulated tablet orally QD, and placebo for ezetimibe over-encapsulated tablet orally QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history. |
| Atorvastatin 40 mg | ACTIVE_COMPARATOR | Participants, who were receiving atorvastatin 20 mg over-encapsulated tablets orally at baseline, received atorvastatin 40 mg over-encapsulated tablets orally once daily (QD), placebo for alirocumab SC injection every two weeks (Q2W), and placebo for ezetimibe over-encapsulated tablets orally QD added to stable Lipid-Modifying Therapy (LMT) for 24 weeks. |
| Ezetimibe 10 mg + Atorvastatin 20 mg | ACTIVE_COMPARATOR | Participants, who were receiving atorvastatin 20 mg over-encapsulated tablets orally at baseline, received ezetimibe 10 mg over-encapsulated tablets orally QD, atorvastatin 20 mg over-encapsulated tablets orally QD, and placebo for alirocumab SC injection Q2W added to stable LMT for 24 weeks. |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg | EXPERIMENTAL | Participants, who were receiving atorvastatin 20 mg over-encapsulated tablets orally at baseline, received Alirocumab 75 mg SC injection Q2W, atorvastatin 20 mg over-encapsulated tablets orally QD, and placebo for ezetimibe over-encapsulated tablets orally QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history. |
| Atorvastatin 80 mg | ACTIVE_COMPARATOR | Participants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received Atorvastatin 80 mg over-encapsulated tablets orally QD, placebo for alirocumab SC injection Q2W, and placebo for ezetimibe over-encapsulated tablets orally QD added to stable LMT for 24 weeks. |
| Ezetimibe 10 mg + Atorvastatin 40 mg | ACTIVE_COMPARATOR | Participants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received ezetimibe 10 mg over-encapsulated tablets orally QD, atorvastatin 40 mg over-encapsulated tablets orally QD, and placebo for alirocumab SC injection Q2W added to stable LMT for 24 weeks. |
| Alirocumab 75 mg/ up to 150 mg + Atorvastatin 40 mg | EXPERIMENTAL | Participants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received alirocumab 75 mg SC injection Q2W, atorvastatin 40 mg over-encapsulated tablets orally QD, and placebo for ezetimibe over-encapsulated tablets orally QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history. |
| Arm 1 - Low Dose | EXPERIMENTAL | - |
| Arm 2 - Medium Dose | EXPERIMENTAL | - |
| Arm 3 - High Dose | EXPERIMENTAL | - |
| Arm 4 - Control Dose | EXPERIMENTAL | - |
| Placebo Matched to Alirocumab | PLACEBO_COMPARATOR | Participants who received placebo in parent study (NCT01576484), has received a subcutaneous injection of placebo matched to alirocumab every 2 weeks for 4 years in this study. |
| Alirocumab 150 mg | EXPERIMENTAL | Participants who received alirocumab in parent study (NCT01576484), has received a subcutaneous injection of alirocumab 150 milligram (mg) every 2 weeks for 4 years in this study. |
| GOFm PCSK9 (Cohort 1): Alirocumab From Day 1 | EXPERIMENTAL | Participants with gain-of-function mutation (GOFm) in proprotein convertase subtilisin/kexin type 9 (PCSK9) gene (Cohort 1): Alirocumab 150 mg subcutaneous (SC) injection at Week 0 (Day 1), Week 2 (Day 15), Week 4, 6 and 10 (matching placebo at Week 8, 12 and 14) during the double-blind period (Group A). Afterwards, participants have the possibility to continue in an open-label extension period with 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years. |
| GOFm PCSK9 (Cohort 1): Alirocumab From Day 15 | EXPERIMENTAL | Participants with gain-of-function mutation (GOFm) in proprotein convertase subtilisin/kexin type 9 (PCSK9) gene (Cohort 1): Alirocumab 150 mg subcutaneous (SC) injection at Week 2 (Day 15), Week 4, 6, 8 and 12 (\[matching placebo at Week 0 (Day 1), 10 and 14\]) during the double-blind period (Group B). Afterwards, participants have the possibility to continue in an open-label extension period with 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years. |
| GOFm PCSK9 or LOFm ApoB (Cohort 2): Alirocumab from Day 1 | EXPERIMENTAL | Participants with gain-of-function mutation (GOFm) in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene or loss-of-function mutation (LOFm) in the apolipoprotein (Apo) B gene (Cohort 2): Alirocumab 150 mg subcutaneous (SC) injection at Week 0 (Day 1), Week 2 (Day 15), Week 4, 6 and 10 (matching placebo at Week 8, 12 and 14) during the double-blind period (Group C). Afterwards, participants have the possibility to continue in an open-label extension period with 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years. |
| GOFm PCSK9 or LOFm ApoB (Cohort 2): Alirocumab from Day 15 | EXPERIMENTAL | Participants with gain-of-function mutation (GOFm) in proprotein convertase subtilisin/kexin type 9 (PCSK9) gene or loss-of-function mutation (LOFm) in apolipoprotein (Apo) B gene (Cohort 2): Alirocumab 150 mg subcutaneous (SC) injection at Week 2 (Day 15), Week 4, 6, 8 and 12 (\[matching placebo at Week 0 (Day 1), 10 and 14\]) during the double-blind period (Group D). Afterwards, participants have the possibility to continue in an open-label extension period with 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years. |
| Placebo | PLACEBO_COMPARATOR | Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks. |
| Alirocumab 150 mg Q4W | EXPERIMENTAL | Alirocumab 150 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks. |
| Alirocumab 200 mg Q4W | EXPERIMENTAL | Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks. |
| Alirocumab 300 mg Q4W | EXPERIMENTAL | Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks. |
| Alirocumab 150 mg Q2W | EXPERIMENTAL | Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks. |
| Alirocumab | EXPERIMENTAL | Critically ill participants with sepsis leading to cardiovascular and/or respiratory failure who are randomized to receive alirocumab. |
| Name | Type | Description |
|---|---|---|
| Alirocumab | DRUG | Alirocumab SC Q2W |
| Placebo | DRUG | Matching placebo SC Q2W |
| Placebo (for alirocumab) | DRUG | Solution for injection, subcutaneous injections in the abdomen, thigh, or outer area of upper arm with an auto-injector. |
| Statin | DRUG | Atorvastatin, rosuvastatin and simvastatin at stable dose in participants with stable statin therapy |
| Rosuvastatin | DRUG | Rosuvastatin over-encapsulated tablets orally. |
| Ezetimibe | DRUG | Ezetimibe over-encapsulated tablets orally. |
| Atorvastatin | DRUG | Atorvastatin over-encapsulated tablets orally. |
| Placebo Matched to Alirocumab | DRUG | Placebo matched to alirocumab was supplied in a pre-filled syringe and administered subcutaneously (SC) in the abdomen, thigh, or outer upper arm; REGN727(SAR236553) is an anti-PCSK9 (proprotein convertase subtilisin/kexin type 9) antibody |
Note: The information listed below is not intended to contain all considerations relevant to a patient's potential participation in this clinical trial, therefore not all inclusion/exclusion criteria are listed. Key Inclusion Criteria 1. Diagnosis of HoFH by at least 1 of the following genotype or...
Alirocumab is used for Homozygous Familial Hypercholesterolemia, Heterozygous Familial Hypercholesterolemia, Hypercholesterolemia, Non-small Cell Lung Cancer (NSCLC), and Sepsis. It is a small molecule being developed by Regeneron Pharmaceuticals, Inc. (REGN) and is currently in Phase 3 clinical development.
Alirocumab targets the proprotein convertase subtilisin kexin 9 (PCSK9) gene, as indicated in clinical trials involving participants with gain-of-function mutations of the PCSK9 gene. It is being studied for its effects on cholesterol levels in patients with hypercholesterolemia.
Alirocumab is developed by Regeneron Pharmaceuticals, Inc., which trades under the ticker symbol REGN. The company is conducting clinical trials for the drug across multiple indications, including familial hypercholesterolemia and sepsis.
Alirocumab is in Phase 3 clinical development, with trials completed in patients with Heterozygous Familial Hypercholesterolemia. It is investigational and not yet approved, as it is still undergoing clinical trials to evaluate its safety and efficacy.
Alirocumab has been studied in several clinical trials, including NCT01266876 for Hypercholesterolemia, NCT01604824 for Hypercholesterolemia with PCSK9 mutations, NCT02326220 for Heterozygous Familial Hypercholesterolemia, and NCT05469347 for Sepsis. These trials have been completed.
Alirocumab and Cemiplimab are the same drug, with Alirocumab being the primary name and Cemiplimab an alternative name. This drug is being developed by Regeneron Pharmaceuticals, Inc. for multiple indications, including hypercholesterolemia and non-small cell lung cancer.