Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
alirocumab SAR236553 · 11 trials · 2 indications
Adjusted least square (LS) means and standard errors were obtained from the mixed model analysis with repeated measures (MMRM) to account for missing data using all available post-baseline data from Week 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis).
Adjusted least square (LS) means and standard errors (SE) were obtained from mixed-effect model with repeated measures (MMRM) model. All post-baseline data available up to Week 24 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model.
SYDNEY-associated PTC was defined as any complaint reported on the participant complaint form that triggered an investigation by the device department and was categorized as either device-related, participant-related, or undetermined whether or not associated with an adverse event (AE). Overall category included total of all 3 types of PTCs. The percentage of SYDNEY-associated PTCs was calculated as: Number of PTCs / Number of unsupervised injections\*100. The confidence interval (CI) was calculated using the Wilson score method.
SYDNEY-associated PTC was defined as any complaint reported on the participant complaint form that triggered an investigation by the device department and was categorized as either device-related, participant-related, or undetermined whether or not associated with an AE.
Adverse Event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Treatment-emergent AEs (TEAEs) were defined as AEs that that developed or worsened or became serious during the TEAE period (time from the first injection of study drug up to the day of the last injection of study drug + 14 days). A Serious Adverse Event (SAE) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event.
Percent change in calculated LDL-C was defined as 100\*(calculated LDL-C value at Week 8 - calculated LDL-C value at baseline)/calculated LDL-C value at baseline. All available baseline and post-baseline calculated LDL-C value during the OLDFI efficacy treatment period \& within one of the analysis windows up to Week 8 were used in the model. OLDFI efficacy treatment period was defined as the period from first investigational medicinal product (IMP) injection to last OLDFI IMP injection + 21 days(for Cohorts 1 \& 2) or +35 days (for Cohorts 3 \& 4). Adjusted Least-squares (LS) mean \& standard error (SE) at Week 8 were obtained from mixed-effect model with repeated measures (MMRM) analysis, with fixed categorical effects of alirocumab dose/dose regimen (30 mg Q2W \[\<50 kg\], 40 mg Q2W \[\<50 kg\], 50 mg Q2W \[\>=50 kg\], 75 mg Q2W \[\>=50 kg\], 75 mg Q4W \[\<50 kg\],150 mg Q4W \[\>=50 kg\], 150 mg Q4W \[\<50 kg\] and 300 mg Q4W (\[\>=50 kg\] dose), time point \& dose/dose regimen-by-time point interaction.
| Arm | Type | Description |
|---|---|---|
| Alirocumab | EXPERIMENTAL | Participants with BW less than (\<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 75 mg Q2W for 48 weeks. Alirocumab dose was up-titrated to 150 mg Q2W from Week 12 in case of increase in BW with BW greater than or equal to \[\>=\] 50 kg. Participants with BW \>=50 kg received SC injection of alirocumab 150 mg Q2W for 48 weeks. |
| Placebo/Alirocumab Q2W | EXPERIMENTAL | Participants received subcutaneous (SC) injection of placebo (matched to alirocumab) based on their body weight (BW) (less than \[\<\] 50 kilograms \[kg\] or greater than or equal to \[\>=\] 50 kg) Q2W for 24 weeks in DB treatment period added to stable LMT. After completion of DB treatment period, eligible participants entered into OL treatment period and received alirocumab 40 milligrams (mg) (for BW \<50 kg) or 75 mg (for BW \>=50 kg) Q2W from Week 24 up to an additional 80 weeks (i.e., up to Week 104) added to stable LMT. After Week 24, dose up-titrated from 40 mg to 75 mg when BW increased from \<50 kg to \>=50 kg. From Week 32 up to Week 104, based on participant LDL-C value, alirocumab dose was either up-titrated as 40 mg to 75 mg (for BW \<50 kg) or 75 mg to 150 mg (for BW \>=50 kg) or down titrated as 75 mg to 40 mg (for BW \<50 kg) or 150 mg to 75 mg (for BW \>=50 kg). |
| Alirocumab Q2W | EXPERIMENTAL | Participants received SC injection of alirocumab 40 mg (for BW \<50 kg) or 75 mg (for BW \>=50 kg) Q2W for 24 weeks in DB treatment period added to stable LMT. Alirocumab dose was up-titrated to 75 mg or 150 mg Q2W from Week 12, when LDL-C level was \>=110 milligrams per deciliter (mg/dL) (2.85 millimoles per liter \[mmol/L\]) at Week 8. After completion of DB treatment period, eligible participants entered into OL treatment period and received alirocumab 40 mg (for BW \<50 kg) or 75 mg (for BW \>=50 kg) from Week 24 up to an additional 80 weeks (i.e., up to Week 104) added to stable LMT. After Week 24, dose up-titrated from 40 mg to 75 mg when BW increased from \<50 kg to \>=50 kg. From Week 32 up to Week 104, based on participant LDL-C value, alirocumab dose was either up-titrated as 40 mg to 75 mg (for BW \<50 kg) or 75 mg to 150 mg (for BW \>=50 kg) or down titrated as 75 mg to 40 mg (for BW \<50 kg) or 150 mg to 75 mg (for BW \>=50 kg). |
| Placebo/Alirocumab Q4W | EXPERIMENTAL | Participants received SC injection of placebo (matched to alirocumab) based on their BW (\<50 kg or \>=50 kg) Q4W for 24 weeks in DB treatment period added to stable LMT. After completion of DB treatment period, eligible participants entered into OL treatment period and received alirocumab 150 mg (for BW \<50 kg) or 300 mg (for BW \>=50 kg) Q4W from Week 24 up to an additional 80 weeks (i.e., up to Week 104) added to stable LMT. After Week 24, dose up-titrated from 150 mg to 300 mg when BW increased from \<50 kg to \>=50 kg. From Week 32 up to Week 104, based on participant LDL-C value, alirocumab dose was either up-titrated as 150 mg Q4W to 75 mg Q2W (for BW \<50 kg) or 300 mg Q4W to 150 mg Q2W (for BW \>=50 kg) or down titrated as 75 mg Q2W to 40 mg Q2W (for BW \<50 kg) or 150 mg Q2W to 75 mg Q2W (for BW \>=50 kg). |
| Alirocumab Q4W | EXPERIMENTAL | Participants received SC injection of alirocumab 150 mg (for BW \<50 kg) or 300 mg (for BW \>=50 kg) Q4W for 24 weeks in DB treatment period added to stable LMT. Alirocumab dose was up-titrated to 75 mg or 150 mg Q2W from Week 12, when LDL-C level \>=110 mg/dL (2.85 mmol/L) at Week 8. After completion of DB treatment period, eligible participants entered into OL treatment period and received alirocumab 150 mg (for BW \<50 kg) or 300 mg (for BW \>=50 kg) from Week 24 up to an additional 80 weeks (i.e., up to Week 104) added to stable LMT. After Week 24, dose up-titrated from 150 mg to 300 mg when BW increased from \<50 kg to \>=50 kg. From Week 32 up to Week 104, based on participant LDL-C value, alirocumab dose was either up-titrated as 150 mg Q4W to 75 mg Q2W (for BW \<50 kg) or 300 mg Q4W to 150 mg Q2W (for BW \>=50 kg) or down titrated as 75 mg Q2W to 40 mg Q2W (for BW \<50 kg) or 150 mg Q2W to 75 mg Q2W (for BW \>=50 kg). |
| Auto-Injector Device (AI) | EXPERIMENTAL | Alirocumab 300 milligram (mg) subcutaneous (SC) injection on Week 0 (Day 1), self-administered using AI device, on-site under supervision in the parallel arm treatment period of 4 weeks. From Week 4, participants switched to other arm of SYDNEY device to receive Alirocumab 300 mg, self- administered (unsupervised) using new auto-injector device (SYDNEY) every 4 weeks (Q4W) from Week 4 until Week 16 in the single arm treatment period added to lipid modifying therapy (LMT). |
| New Auto-injector Device (SYDNEY) | EXPERIMENTAL | Alirocumab 300 mg SC injection on Week 0 (Day 1), self-administered using new auto-injector device (SYDNEY), on-site under supervision in the parallel arm treatment period of 4 weeks. From Week 4, same treatment (Alirocumab 300 mg) with the same device (SYDNEY) was self-administered, (unsupervised) Q4W until Week 16 in the single arm treatment period added to LMT. Duration of single arm treatment period was 12 weeks, i.e. from Week 4 to 16. |
| Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | EXPERIMENTAL | Period 1: Participants with body weight less than (\<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 30 milligram(mg) administered every 2 weeks (Q2W) up to 8 weeks added to lipid modifying therapy (LMT). Period 2: Participants with body weight \< 50 kg received SC injection of alirocumab 30 mg administered Q2W from Week 16 until they started receiving dose matching to Cohort 2 dosage including dose adjustment to body weight as required. Cohort 2 dosage was: if body weight was still \< 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was \> = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. |
| Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | EXPERIMENTAL | Period 1: Participants with body weight greater than or equal to (\>=) 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 50 mg administered Q2W from Week 16 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130. |
| Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | EXPERIMENTAL | Period 1: Participants with body weight \< 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight \< 50 kg received SC injection of alirocumab 40 mg administered Q2W from Week 16 until switch of dosage in Cohorts 1 and 3. If body weight was still \< 50 kg, participants continued to receive SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was \> = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. |
| Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | EXPERIMENTAL | Period 1: Participants with body weight \>= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 75 mg administered Q2W from Week 16 until Week 130. |
| Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | EXPERIMENTAL | Period 1: Participants with body weight \< 50 kg received SC injection of alirocumab 75 mg administered every 4 weeks (Q4W) up to 8 weeks added to LMT. Period 2: Participants with body weight \< 50 kg received SC injection of alirocumab 75 mg administered Q4W from Week 14 until switch to Cohort 2 dosage including dose adjustment to body weight as required, then Cohort 2 dosage: if body weight was still \< 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was \> = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. |
| Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | EXPERIMENTAL | Period 1: Participants with body weight \>= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT. Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 150 mg administered Q4W from Week 14 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130. |
| Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | EXPERIMENTAL | Period 1: Participants with body weight \< 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. Period 2: Participants with body weight \< 50 kg received SC injection of Alirocumab 150 mg administered Q4W from Week 12 until Week 48. |
| Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg | EXPERIMENTAL | Period 1: Participants with body weight \>= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 300 mg administered Q4W from Week 12 until Week 48. |
| Placebo | PLACEBO_COMPARATOR | Subcutaneous injection of a single dose of matching placebo |
| alirocumab SAR236553 (REGN727) - Dose A | EXPERIMENTAL | alirocumab SAR236553 (REGN727) - Dose A - Injection in healthy subjects through subcutaneous administration in the abdomen. alirocumab SAR236553 (REGN727) is a fully human monoclonal antibody that binds PCSK9 (proprotein convertase subtilisin/kexin type 9) |
| alirocumab SAR236553 (REGN727) - Dose B | EXPERIMENTAL | alirocumab SAR236553 (REGN727) - Dose B - Injection in healthy subjects through subcutaneous administration in the upper arm. |
| alirocumab SAR236553 (REGN727) - Dose C | EXPERIMENTAL | alirocumab SAR236553 (REGN727) - Dose C - Injection in healthy subjects through subcutaneous administration in the thigh. |
| alirocumab SAR236553 (REGN727) - mild hepatic function | EXPERIMENTAL | Injection through subcutaneous (SC) administration in patients with mild hepatic function |
| alirocumab SAR236553 (REGN727) - moderate hepatic function | EXPERIMENTAL | Injection through subcutaneous (SC) administration in patients with moderate hepatic function |
| alirocumab SAR236553 (REGN727) - normal hepatic function | EXPERIMENTAL | Injection through subcutaneous (SC) administration in patients with normal hepatic function |
| alirocumab SAR236553 (REGN727) (Formulation A x 1) | EXPERIMENTAL | A single subcutaneous injection of Formulation A |
| alirocumab SAR236553 (REGN727) (Formulation B x 1) | EXPERIMENTAL | A single subcutaneous injection of Formulation B |
| alirocumab SAR236553 (REGN727) (Formulation A x 2) | EXPERIMENTAL | 2 single subcutaneous injections of Formulation A |
| Name | Type | Description |
|---|---|---|
| Alirocumab SAR236553 (REGN727) | DRUG | Pharmaceutical form: solution for injection in pre-filled syringe, Route of administration: subcutaneous (SC) |
| Atorvastatin | DRUG | Pharmaceutical form: tablet, Route of administration: oral |
| Simvastatin | DRUG | Pharmaceutical form: tablet, Route of administration: oral |
| Fluvastatin | DRUG | Pharmaceutical form: capsule, Route of administration: oral |
| Pravastatin | DRUG | Pharmaceutical form: tablet, Route of administration: oral |
| Lovastatin | DRUG | Pharmaceutical form: tablet, Route of administration: oral |
| Rosuvastatin | DRUG | Pharmaceutical form: tablet, Route of administration: oral |
| Ezetimibe | DRUG | Pharmaceutical form: tablet, Route of administration: oral |
| Cholestyramine | DRUG | Pharmaceutical form: oral suspension, Route of administration: oral |
| Nicotinic acid | DRUG | Pharmaceutical form: tablet, Route of administration: oral |
| Fenofibrate | DRUG | Pharmaceutical form: tablet, Route of administration: oral |
| Omega-3 fatty acids | DRUG | Pharmaceutical form: capsule, Route of administration: oral |
| Placebo | DRUG | Pharmaceutical form:solution Route of administration: subcutaneous injection |
| Alirocumab SAR236553 | DRUG | Pharmaceutical form: Solution for injection Route of administration: Subcutaneous |
| Current auto-injector device (AI) | DEVICE | Pharmaceutical form: Route of administration: Subcutaneous self-administration of alirocumab |
| New auto-injector device (SYDNEY) | DEVICE | Pharmaceutical form: Route of administration: Subcutaneous self-administration of alirocumab |
| placebo (for injection training only) | DRUG | Pharmaceutical form:solution Route of administration: subcutaneous |
| statins | DRUG | Pharmaceutical form: tablet Route of administration: oral |
Inclusion criteria : * Participants genetically diagnosed with hoFH. * Participants treated with optimal dose of statin +/- other lipid modifying therapies (LMTs), or non-statin LMTs if statin-intolerant at stable dose(s) for at least 4 weeks. * A signed informed consent indicating parental permiss...
Alirocumab SAR236553 is used for hypercholesterolaemia, also known as hypercholesterolemia. It is being studied in patients with high cholesterol, including children and adolescents with heterozygous familial hypercholesterolemia, and in adults with high or very high cardiovascular risk whose cholesterol is not adequately controlled with lipid-modifying therapy.
Alirocumab SAR236553 is developed by Sanofi, which trades under the ticker SNY. The company is conducting clinical trials to evaluate the drug's efficacy and safety in treating hypercholesterolaemia across various patient populations.
Alirocumab SAR236553 is in Phase 3 clinical development. It has completed Phase 1, Phase 2, and Phase 3 trials, with all eight trials completed and no active trials currently ongoing. The drug remains investigational and is not yet approved.
Alirocumab SAR236553 has completed eight clinical trials, including NCT01443650, a Phase 1 study in healthy subjects; NCT02890992, a Phase 2 dose-finding study in children; and NCT03415178 and NCT03510884, both Phase 3 studies. All trials are completed, with total enrollment of 1,220 participants.
Yes, alirocumab SAR236553 is also known as SAR236553. The drug is referred to by both names in clinical trial records, and they represent the same investigational therapy being developed by Sanofi for hypercholesterolaemia.
Alirocumab SAR236553 is a small molecule being developed for hypercholesterolaemia. Its specific molecular target is not disclosed in the available information, so its mechanism of action is not described here.