Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication EVKEEZA is indicated as an adjunct to diet and exercise and other low-density lipoprotein-cholesterol (LDL-C) lowering therapies to reduce LDL-C in adults and pediatric patients, aged 1 year and older, with homozygous familial hypercholesterolemia (HoFH). FDA label
Also known as evinacumab, EVKEEZA®
REGN1500 · 8 trials · 5 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.
Percent change was reported for low-density lipoprotein cholesterol (LDL-C) from baseline (week 0) up to week 4. LDL-C was measured using conventional units mg/dL. The efficacy analysis set included all participants in the safety analysis set (SAF) who had baseline and at least 1 post-baseline measure of the lipid panel in the main study period.
Safety of REGN1500 will be assessed by physical examination, vital signs, electrocardiogram (ECG), and clinical laboratory evaluations from visit 1 to day 183 \[EOS (end of study)\]
| 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 |
| Open-label | EXPERIMENTAL | Open-label REGN1500 |
| dosing cohort 1 | EXPERIMENTAL | Patients will receive REGN1500 or placebo in dosing cohort 1 |
| dosing cohort 2 | EXPERIMENTAL | Patients will receive REGN1500 or placebo in dosing cohort 2 |
| dosing cohort 3 | EXPERIMENTAL | Patients will receive REGN1500 or placebo in dosing cohort 3 |
| dosing cohort 4 | EXPERIMENTAL | Patients will receive REGN1500 or placebo in dosing cohort 4 |
| dosing cohort 5 | EXPERIMENTAL | Patients will receive REGN1500 or placebo in dosing cohort 5 |
| Group A: Cohorts 1 through 6 | EXPERIMENTAL | Group A: Cohorts 1 through 3 will receive REGN1500 subcutaneous (SC) or placebo Cohorts 4 through 6 will receive REGN1500 intravenous (IV) or placebo |
| Group B | EXPERIMENTAL | Group B will receive REGN1500 IV or placebo |
| Group C: Cohorts 1 and 2 | EXPERIMENTAL | Group C: Cohort 1 will receive REGN1500 SC or placebo Cohort 2 will receive REGN1500 IV or placebo |
| 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. |
| REGN1500 250 mg SC/15 mg/kg IV/450 mg SC | DRUG | Participants received single dose of REGN1500 subcutaneous (SC) injection of 250 milligrams (mg) at Week 0 (Day 1), followed by single dose of REGN1500 intravenous (IV) injection of 15 milligrams per kilogram (mg/kg) at Week 2 (Day 15) and then followed by 4 doses of REGN1500 SC injection of 450 mg once weekly starting from Week 12 (Day 85). Only the first 2 enrolled participants received 4 weekly REGN1500 450 mg SC doses at weeks 12, 13, 14, and 15 per the protocol. This dose regimen was removed under protocol amendment 4. Participants were followed for a period of 24 weeks (through Week 26 \[Day 183\]) after the last dose of study drug in the main study period. |
| REGN1500 | DRUG | - |
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...
REGN1500 is an investigational small molecule being studied for homozygous familial hypercholesterolemia, hypertriglyceridemia, and metabolic disorders. It has been evaluated in a Phase 2 study in participants with homozygous familial hypercholesterolemia and in Phase 1 studies in hypertriglyceridemia and metabolic disorders. It is not approved for any indication.
REGN1500 targets Angptl-3, a protein also known as angiopoietin-like 3. Angptl-3 is involved in regulating plasma lipid levels, which is the basis for studying REGN1500 in lipid and metabolic conditions such as homozygous familial hypercholesterolemia and hypertriglyceridemia.
REGN1500 is being developed by Regeneron Pharmaceuticals, Inc., which trades on the Nasdaq under the ticker REGN. Regeneron is the sponsor of the clinical studies evaluating REGN1500 in lipid and metabolic disorders.
REGN1500 has completed Phase 2 development. A Phase 2 study in participants with homozygous familial hypercholesterolemia is listed as completed, along with two completed Phase 1 studies. REGN1500 is investigational and has not been approved by the FDA for any indication.
REGN1500 has been studied in three completed trials: NCT02265952, a Phase 2 study in homozygous familial hypercholesterolemia conducted in the United States, Canada, and the Netherlands; NCT02107872, a Phase 1 multiple ascending dose study in metabolic disorders; and NCT01749878, a Phase 1 single dose study in hypertriglyceridemia.