Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Evinacumab · 6 trials · 4 indications
Cmax was obtained directly from the plasma concentration versus time curve.
AUClast was defined as area under the serum concentration time-curve from zero to the last measured concentration.
T1/2 was defined as the time required for the plasma concentration of drug to decrease 50 percent in the final stage of its elimination.
Percent change was calculated as 100 multiplied by (calculated LDL-C value at Week 24 minus calculated LDL-C value at baseline) divided by calculated LDL-C value at baseline.
The safety analysis set (SAF) included all participants who were enrolled and received at least 1 dose or part of a dose of open-label study treatment.
Percent change was calculated as 100x(calculated LDL-C value at Week 24 - calculated LDL-C value at baseline)/calculated LDL-C value at baseline. The baseline LDL-C value was the last calculated LDL-C value obtained before the first dose of double-blind-study drug. The calculated LDL-C at week 24 was the LDL-C value obtained within the week 24 efficacy analysis window, regardless of adherence to treatment and subsequent therapies (intent-to-treat \[ITT\] estimand). The ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).
For participants randomized to evinacumab treatment group, baseline (Week 0) TG was defined as the geometric mean of all available TG results at day -28, day -14 and week 0; for participants randomized to placebo treatment group, baseline (Week 12) TG was defined as the geometric mean of all available TG results at weeks 6, 8, and 12.
| Arm | Type | Description |
|---|---|---|
| Evinacumab | EXPERIMENTAL | Part A: Single intravenous (IV) dose Part B: IV dose every 4 weeks (Q4W) until week 20 Part C: IV dose Q4W |
| Placebo | EXPERIMENTAL | - |
| Group A: dosing regimen 1 | EXPERIMENTAL | SC Evinacumab QW for 16 weeks |
| Group A: dosing regimen 2 | EXPERIMENTAL | SC Evinacumab Q2W for 16 weeks (alternating with matching placebo on opposite weeks) |
| Group A: dosing regimen 3 | EXPERIMENTAL | SC Evinacumab QW for 16 weeks |
| Group A: matching placebo | EXPERIMENTAL | Placebo SC QW for 16 weeks |
| Group B: dosing regimen 1 | EXPERIMENTAL | Intravenous (IV) Evinacumab Q4W for 24 weeks |
| Group B: dosing regimen 2 | EXPERIMENTAL | IV Evinacumab Q4W for 24 weeks |
| Group B: matching placebo | EXPERIMENTAL | Placebo IV Q4W for 24 weeks |
| Cohort 1 | EXPERIMENTAL | Evinacumab SC or placebo SC |
| Cohort 2 | EXPERIMENTAL | Low dose regimen: evinacumab IV or placebo IV |
| Cohort 3 | EXPERIMENTAL | High dose regimen: evinacumab IV or placebo IV |
| Cohort 4 | EXPERIMENTAL | Evinacumab or placebo SC every week (QW) x 8 doses |
| Cohort 5 | EXPERIMENTAL | Evinacumab or placebo SC x 1 dose |
| Name | Type | Description |
|---|---|---|
| Evinacumab | DRUG | Part A: Single IV dose Part B \& C: IV dose Q4W |
| Placebo | DRUG | IV administration of placebo |
| Matching placebo | DRUG | SC or IV administration |
| Background Lipid Modifying Therapy (LMT) | OTHER | All participants should be on a stable, maximally tolerated statin throughout the duration of the study. The dose of statin and of PCSK9 inhibitor, such as alirocumab or evolocumab, as well as other LMT (if applicable), should remain stable throughout the study duration, from screening through the end of study (EOS) visit. |
Key Inclusion Criteria: 1. Diagnosis of functional HoFH by either genetic or clinical criteria as defined in the protocol 2. LDL-C \>130 mg/dL at the screening visit 3. Body weight ≥15 kg 4. Receiving stable maximally tolerated therapy\*at the screening visit \*Maximally tolerated therapy could inc...
Evinacumab is an investigational monoclonal antibody developed by Regeneron Pharmaceuticals, Inc. (ticker REGN). It is being studied for homozygous familial hypercholesterolemia, hypercholesterolemia, and severe hypertriglyceridemia. The program includes completed Phase 2 and Phase 3 trials in patients with these lipid disorders.
Evinacumab targets ANGPTL3, also known as angiopoietin-like protein 3. It is an inhibitor of ANGPTL3, meaning it binds and blocks the activity of this protein. ANGPTL3 regulates lipid metabolism, and inhibiting it is the intended mechanism for lowering cholesterol and triglyceride levels in patients with severe lipid disorders.
Evinacumab is developed by Regeneron Pharmaceuticals, Inc., which trades under the ticker REGN. Regeneron is the sponsor of the clinical trials evaluating the drug in homozygous familial hypercholesterolemia and severe hypertriglyceridemia.
Evinacumab has completed Phase 2 and Phase 3 clinical trials. The program includes three completed Phase 3 studies and one completed Phase 2 study, with no active trials currently listed. It is an investigational monoclonal antibody and is not described as approved.
Evinacumab has been studied in completed trials including NCT03399786 and NCT03409744 in homozygous familial hypercholesterolemia, NCT04233918 in pediatric homozygous familial hypercholesterolemia, and NCT03452228 in severe hypertriglyceridemia at risk for acute pancreatitis. These trials enrolled a combined total of 253 patients across multiple countries.
Evinacumab is being developed for the treatment of homozygous familial hypercholesterolemia, a severe inherited condition causing very high cholesterol levels. Clinical trials have evaluated it in both adult and pediatric patients with this condition, including a Phase 3 study in children aged 5 years and older and a long-term Phase 3 safety and efficacy study.