Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Obicetrapib, Monotherapy obicetrapib
obicetrapib+ ezetimibe daily · 14 trials · 20 indications
Total plaque comparison measured by CCTA
LS mean percent change in low-density lipoprotein cholesterol (LDL-C) from baseline to Day 84 in the obicetrapib 10 mg/ezetimibe 10 mg fixed-dose combination (FDC) group compared to the placebo group. LDL-C level was measured by preparative ultracentrifugation (PUC).
LS mean percent change in low-density lipoprotein cholesterol (LDL-C) from baseline to Day 84 in the obicetrapib 10 mg/ezetimibe 10 mg fixed-dose combination (FDC) group compared to the ezetimibe monotherapy 10 mg group. LDL-C level was measured by preparative ultracentrifugation (PUC).
LS mean percent change in low-density lipoprotein cholesterol (LDL-C) from baseline to Day 84 in the obicetrapib 10 mg/ezetimibe 10 mg fixed-dose combination (FDC) group compared to the obicetrapib monotherapy 10 mg group. LDL-C level was measured by preparative ultracentrifugation (PUC).
LS mean percent change in low-density lipoprotein cholesterol (LDL-C) from baseline to Day 84 in the obicetrapib 10 mg group compared to the placebo group. LDL-C level was measured by preparative ultracentrifugation (PUC).
LS mean percent change from baseline to Day 84 in Low-Density Lipoprotein Cholesterol (LDL-C) in the obicetrapib group compared to the placebo group \[PUC\]. LDL-C level was measured by preparative ultracentrifugation (PUC).
To evaluate the effect of obicetrapib on the risk of MACE
The primary efficacy endpoint is the effect of obicetrapib on the sum of the percent changes in lutein, zeaxanthin, and α-tocopherol levels within HDL particles from baseline to visit 4 (week 16) compared to placebo.
Lp(a) change on combination therapy
Mean percent change from Day 1 to Day 56 in Low-Density Lipoprotein Cholesterol (LDL-C) for each obicetrapib group compared to the placebo group. LDL-C was calculated using the Friedewald equation unless TG≥400 mg/dL or LDL-C ≤50 mg/dL; if TG ≥400 mg/dL or LDL-C ≤50 mg/dL, then LDL-C level was measured directly by preparative ultracentrifugation (PUC).
Median percent change from Day 1 to Day 56 in Low-Density Lipoprotein Cholesterol (LDL-C) for each obicetrapib group compared to the placebo group. LDL-C was calculated using the Friedewald equation unless TG≥400 mg/dL or LDL-C ≤50 mg/dL; if TG ≥400 mg/dL or LDL-C ≤50 mg/dL, then LDL-C level was measured directly by preparative ultracentrifugation (PUC).
LS Mean percent change from Day 1 to Day 56 in Low-Density Lipoprotein Cholesterol (LDL-C) for each obicetrapib group compared to the placebo group. LDL-C was calculated using the Friedewald equation unless TG≥400 mg/dL or LDL-C ≤50 mg/dL; if TG ≥400 mg/dL or LDL-C ≤50 mg/dL, then LDL-C level was measured directly by preparative ultracentrifugation (PUC).
Mean Percent change from Day 1 to Day 56 in Low-Density Lipoprotein Cholesterol (LDL-C) for each obicetrapib group compared to the placebo group. LDL-C level was measured by preparative ultracentrifugation (PUC).
Median Percent change from Day 1 to Day 56 in Low-Density Lipoprotein Cholesterol (LDL-C) for each obicetrapib group compared to the placebo group. LDL-C level was measured by preparative ultracentrifugation (PUC)
Mean Percent change from Day 1 to Day 56 in Low-Density Lipoprotein Cholesterol (LDL-C) for each obicetrapib group compared to the placebo group. LDL-C level was measured by preparative ultracentrifugation (PUC).
Mean percent change from Day 1 to Day 84 in Low-Density Lipoprotein Cholesterol (LDL-C) for the obicetrapib 10 mg + ezetimibe 10 mg combination treatment group compared with the placebo group. LDL-C was calculated using the Friedewald equation unless TG ≥400 mg/dL or LDL-C ≤50 mg/dL; if TG ≥400 mg/dL or LDL-C ≤50 mg/dL, then LDL-C level was measured directly by preparative ultracentrifugation (PUC).
Median percent change from Day 1 to Day 84 in Low-Density Lipoprotein Cholesterol (LDL-C) for the obicetrapib 10 mg + ezetimibe 10 mg combination treatment group compared with the placebo group. LDL-C was calculated using the Friedewald equation unless TG ≥400 mg/dL or LDL-C ≤50 mg/dL; if TG ≥400 mg/dL or LDL-C ≤50 mg/dL, then LDL-C level was measured directly by preparative ultracentrifugation (PUC).
LS Mean percent change from Day 1 to Day 84 in Low-Density Lipoprotein Cholesterol (LDL-C) for the obicetrapib 10 mg + ezetimibe 10 mg combination treatment group compared with the placebo group. LDL-C was calculated using the Friedewald equation unless TG ≥400 mg/dL or LDL-C ≤50 mg/dL; if TG ≥400 mg/dL or LDL-C ≤50 mg/dL, then LDL-C level was measured directly by preparative ultracentrifugation (PUC).
Mean percent change from Day 1 to Day 84 in Low-Density Lipoprotein Cholesterol (LDL-C) for the obicetrapib 10 mg + ezetimibe 10 mg combination treatment group compared with the placebo group. LDL-C level was measured by preparative ultracentrifugation (PUC).
Median percent change from Day 1 to Day 84 in Low-Density Lipoprotein Cholesterol (LDL-C) for the obicetrapib 10 mg + ezetimibe 10 mg combination treatment group compared with the placebo group. LDL-C level was measured by preparative ultracentrifugation (PUC).
LS Mean percent change from Day 1 to Day 84 in Low-Density Lipoprotein Cholesterol (LDL-C) for the obicetrapib 10 mg + ezetimibe 10 mg combination treatment group compared with the placebo group. LDL-C level was measured by preparative ultracentrifugation (PUC).
Mean percent change from screening (V1) to end of treatment (V6) in ApoA-I in CSF
Mean percent change in ApoA-I in plasma from baseline (V2) to week 24 (V6)
Mean percent change from screening (V1) to end of treatment (V6) in ApoE
Mean percent change from baseline (V2) to week 24 (V6) in plasma in ApoE
Small high-density lipoprotein (s-HDL) particle concentration in cerebrospinal fluid (CSF) measured by Ion Mobility Assay (https://doi.org/10.1002/alz.12649)
Small high-density lipoprotein (s-HDL) particle concentration in CSF measured by Ion Mobility Assay (https://doi.org/10.1002/alz.12649)
Small high-density lipoprotein (s-HDL) particle concentration plasma measured by Ion Mobility Assay. For more information on the measurement used please refer to this article: https://doi.org/10.1002/alz.12649
Small high-density lipoprotein (s-HDL) particle concentration in plasma measured by Ion Mobility Assay at Week 24 For more information on the measurement used please refer to this article: https://doi.org/10.1002/alz.12649
Mean percent change in cholesterol efflux capacity in CSF from screening (V1) to week 24 (V6)
Mean percent change in LDL-C from baseline to Day 57; LDL-C determined using the Friedewald formula
Median percent change in LDL-C from baseline to Day 57; LDL-C determined using the Friedewald formula
LS Mean percent change in LDL-C from baseline to Day 57; LDL-C determined using the Friedewald formula
Mean percent change in LDL-C from baseline to Day 57; LDL-C measured using preparative ultracentrifugation (PUC)
Median percent change in LDL-C from baseline to Day 57; LDL-C measured using preparative ultracentrifugation (PUC)
LS Mean percent change in LDL-C from baseline to Day 57; LDL-C measured using preparative ultracentrifugation (PUC)
LS mean percent change from Day 1 to Day 56 in Low-Density Lipoprotein Cholesterol (LDL-C) for each obicetrapib group compared to the placebo group. \[Friedewald\] LDL-C was calculated using the Friedewald equation unless TG ≥400 mg/dL or LDL-C ≤50 mg/dL; if TG ≥400 mg/dL or LDL-C ≤50 mg/dL, then LDL-C level was measured directly by preparative ultracentrifugation (PUC),
| Arm | Type | Description |
|---|---|---|
| Obicetrapib/Ezetimibe | EXPERIMENTAL | obicetrapib 10 mg + ezetimibe 10 mg FDC daily |
| Obicetrapib | EXPERIMENTAL | obicetrapib 10 mg daily |
| Placebo | PLACEBO_COMPARATOR | Placebo on top of guideline-recommended lipid-lowering therapy |
| Open-Label Extension | EXPERIMENTAL | Open-Label Extension (OLE) with the FDC of Obicetrapib 10 mg and Ezetimibe 10 mg |
| Combination Therapy | EXPERIMENTAL | once-daily obicetrapib 10 mg and ezetimibe 10 mg fixed dose combination tablet, placebo tablet, placebo capsule |
| Monotherapy obicetrapib | EXPERIMENTAL | once-daily obicetrapib 10 mg, placebo tablet, placebo capsule |
| Monotherapy ezetimibe | ACTIVE_COMPARATOR | once-daily ezetimibe 10 mg capsule, 2 placebo tablets |
| Obicetrapib 10 mg | EXPERIMENTAL | one 10 mg Obicetrapib tablet once daily |
| obicetrapib 10mg | EXPERIMENTAL | one 10mg tablet, once daily. |
| obicetrapib/evolocumab combination | EXPERIMENTAL | obicetrapib 10 mg/dL daily for 8 weeks followed by obicetrapib 10 mg/dL daily + evolocumab 140 mg/dL every other week for 8 weeks |
| 2.5 mg Obicetrapib | EXPERIMENTAL | once-daily Obicetrapib |
| 5 mg Obicetrapib | EXPERIMENTAL | once-daily Obicetrapib |
| 10 mg Obicetrapib | EXPERIMENTAL | once-daily Obicetrapib |
| monotherapy | EXPERIMENTAL | once-daily obicetrapib 10 mg tablet and placebo capsule |
| 10mg obicetrapib tablets | EXPERIMENTAL | 10mg obicetrapib (5mg tablets) administered orally daily for 24 weeks |
| Obicetrapib monotherapy | EXPERIMENTAL | 5 mg obicetrapib + placebo ezetimibe; once daily |
| Ezetimibe monotherapy | EXPERIMENTAL | placebo obicetrapib + 10 mg ezetimibe; once daily |
| obicetrapib 5 mg | EXPERIMENTAL | once-daily obicetrapib |
| Name | Type | Description |
|---|---|---|
| obicetrapib 10 mg + ezetimibe 10 mg FDC daily | DRUG | FDC |
| Obicetrapib 10 mg | DRUG | monotherapy |
| Placebo | OTHER | placebo on top of guideline-recommended lipid modifying therapy |
| Combination Therapy | COMBINATION_PRODUCT | tablet; 10mg obicetrapib and 10mg ezetimibe fixed does combination |
| Monotherapy obicetrapib | DRUG | tablet; 10mg obicetrapib |
| Monotherapy ezetimibe | DRUG | capsule; 10mg ezetimibe |
| Combination Therapy placebo | OTHER | tablet; no active ingredient |
| Obicetrapib Placebo | OTHER | tablet; no active ingredient |
| Ezetimibe Placebo | OTHER | capsule; no active ingredient |
| Obicetrapib | DRUG | 10 mg Obicetrapib tablet |
| Matching placebo tablets | DRUG | matching placebo tablet |
| Obicetrapib 10mg | DRUG | Active Drug |
| obicetrapib 10 mg + obicetrapib/evolocumab 140 mg Q 2 weeks | DRUG | 10 mg obicetrapib for 8 weeks followed by 10 mg obicetrapib/ 140 mg evolocumab (every 2 weeks) combination for 8 weeks |
| Ezetimibe 10mg | DRUG | capsules; 10 mg ezetimibe tablets filled into capsule shells, 1 tablet per capsule. |
| Obicetrapib 5mg | DRUG | tablet |
Inclusion Criteria: * fasting serum LDL-C ≥ 70 mg/dL (≥1.81 mmol/L) * Have fasting TG ≥150 mg/dL (≥1.7 mmol/L) and \<400 mg/dL (\<4.5 mmol/L) * Know diagnosis of T2DM OR have metabolic syndrome defined as fasting TG ≥150 mg/dL (≥1.7mmol/L) and \<400 mg/dL (\<4.5 mmol/L) and at least 2 risk factors ...
Obicetrapib is an investigational small molecule developed by NewAmsterdam Pharma Company N.V. (ticker NAMS) for lipid-related conditions, including dyslipidemia and atherosclerotic cardiovascular disease. It is being studied as monotherapy and in fixed-dose combination with ezetimibe, and in combination with evolocumab, across a clinical program that includes multiple Phase 2 and Phase 3 trials.
Obicetrapib targets CETP, cholesteryl ester transfer protein, and acts as a CETP inhibitor. By inhibiting this target, obicetrapib is designed to affect lipid metabolism, and its clinical program includes studies of its effects on lipid levels and on antioxidant levels in plasma and HDL particles.
Obicetrapib is developed by NewAmsterdam Pharma Company N.V., which trades under the ticker NAMS. The company sponsors the obicetrapib clinical program, including trials of obicetrapib monotherapy, obicetrapib combined with ezetimibe as a fixed-dose combination, and obicetrapib combined with evolocumab.
Obicetrapib is in clinical development, with trials spanning Phase 2 and Phase 3. It is investigational and is being studied in indications including dyslipidemia, atherosclerotic cardiovascular disease, preclinical Alzheimer's disease, and antioxidant absorption. The program includes eight trials in total, with two currently active and seven completed.
Obicetrapib trials include NCT07794670, a Phase 2 study in preclinical Alzheimer's disease; NCT07219602, a Phase 3 study of obicetrapib/ezetimibe fixed-dose combination or obicetrapib 10 mg in type 2 diabetes and metabolic syndrome; NCT06982508, a Phase 2 antioxidant study in healthy volunteers; and NCT06496243, a Phase 2 study of obicetrapib and obicetrapib plus Repatha on Lp(a) levels.