Obicetrapib is an oral, highly selective, next-generation inhibitor of cholesteryl ester transfer protein, or CETP. It has been developed to lower elevated low-density lipoprotein cholesterol, or LDL-C, in patients who do not achieve their treatment goals with currently available lipid-lowering therapies.
Obicetrapib is also being investigated to determine whether its effects on LDL-C, apolipoprotein B and other atherogenic lipoproteins translate into fewer myocardial infarctions, strokes, coronary revascularisations and cardiovascular deaths. However, a definitive reduction in cardiovascular events has not yet been established.
On 23 July 2026, the European Medicines Agency’s Committee for Medicinal Products for Human Use, or CHMP, recommended granting marketing authorisations for:
At the time of writing, these are positive CHMP opinions rather than final European Commission marketing authorisations. (European Medicines Agency (EMA))
CETP stands for cholesteryl ester transfer protein. It is a plasma protein involved in the exchange of lipids between different lipoprotein particles.
Under normal circumstances, CETP transfers cholesteryl esters from high-density lipoprotein, or HDL, to apolipoprotein B-containing lipoproteins, particularly very-low-density lipoprotein, or VLDL, and LDL. In exchange, triglycerides are transferred from VLDL and LDL to HDL.
As a result of this process:
This transfer process is physiologically complex. It should therefore not be interpreted simply as CETP moving “good cholesterol” into “bad cholesterol.” HDL, LDL and VLDL are particles with different metabolic functions, and their cholesterol content does not fully describe their biological behaviour.
Obicetrapib binds selectively to CETP and inhibits the transfer of cholesteryl esters from HDL to apoB-containing lipoproteins.
Because less cholesterol is transferred from HDL to VLDL and LDL, a greater amount remains within HDL particles. Consequently, the measured HDL-C concentration rises substantially.
In the major obicetrapib studies, HDL-C increased by more than 100% in some patient populations. However, a higher HDL-C concentration should not automatically be interpreted as equivalent to a clinical benefit. Previous trials of HDL-raising treatments have shown that increasing the amount of cholesterol carried by HDL does not necessarily prevent cardiovascular events.
When CETP is inhibited, less cholesteryl ester is transferred to VLDL and LDL. This contributes to reductions in:
Apolipoprotein B is particularly relevant because each atherogenic LDL, VLDL-remnant or intermediate-density lipoprotein particle generally contains one apoB molecule. A reduction in apoB therefore usually indicates a reduction in the number of circulating atherogenic particles, rather than merely a reduction in the amount of cholesterol carried by each particle.
Potent CETP inhibition also changes the lipid composition and metabolism of LDL particles. Mechanistic studies suggest that CETP inhibition reduces the hepatic cholesterol pool, increases LDL-receptor expression and promotes the removal of LDL particles from the circulation.
This means that the LDL-C reduction may result from both:
The relative contribution of these mechanisms in humans is still being investigated. (PubMed Central (PMC))
Simplified explanation
Without CETP inhibition: CETP transfers cholesteryl esters from HDL to LDL and VLDL.
With obicetrapib: HDL retains more cholesterol, while LDL and other apoB-containing particles contain less cholesterol and may be removed more efficiently by the liver.
The principal lipid effects are therefore:
HDL-C increases, while LDL-C, non-HDL-C, apolipoprotein B and lipoprotein(a) decrease.
For the potential prevention of atherosclerotic cardiovascular disease, the reductions in LDL-C, non-HDL-C and apoB are probably more important than the increase in HDL-C.
This image was created using artificial intelligence.
Intended dosage
The dosage evaluated in the phase III programme and included in the European CHMP recommendation is:
Obicetrapib 10 mg orally once daily.
The fixed-dose combination Evlarco contains:
Obicetrapib 10 mg plus ezetimibe 10 mg once daily.
In the clinical trials, obicetrapib was administered as a once-daily oral tablet. Pharmacokinetic studies indicate that food has no clinically important effect on exposure, supporting administration independently of meals. Nevertheless, the final instructions regarding administration, missed doses, contraindications and dose adjustments will be determined by the approved Summary of Product Characteristics after a final marketing-authorisation decision. (Orange County Research Center)
Obicetrapib is intended primarily as an additional treatment when LDL-C remains above the individual treatment goal despite diet and maximally tolerated lipid-lowering therapy.
It should not generally be regarded as a replacement for an effective and tolerated statin. Statins remain the foundation of lipid-lowering therapy because their ability to reduce cardiovascular morbidity and mortality is supported by extensive outcome evidence.
Why is only one dosage proposed?
Earlier clinical studies investigated several daily doses, including:
These studies demonstrated a clear dose-response relationship. The 10-mg dose produced the most consistent and extensive CETP inhibition and LDL-C reduction while retaining a favourable tolerability profile.
For example, in a Japanese phase II study, the median placebo-adjusted LDL-C reductions with 2.5 mg, 5 mg and 10 mg were approximately 25%, 32% and 46%, respectively. The totality of the phase II evidence supported selection of 10 mg for the phase III development programme.
Therefore:
Obicetrapib also has a long terminal elimination half-life of approximately 131 hours following a 10-mg dose. This supports stable drug exposure with once-daily administration and means that steady state is reached gradually. (SEC)
BROADWAY
BROADWAY was a multinational, randomised, placebo-controlled phase III trial involving 2,530 patients with either:
Participants were already receiving maximally tolerated lipid-lowering therapy. This could include statins, ezetimibe, bempedoic acid or PCSK9 inhibitors.
Patients received either obicetrapib 10 mg once daily or placebo for 365 days.
The mean baseline LDL-C concentration was 98 mg/dL, equivalent to approximately 2.54 mmol/L.
At day 84:
The mean achieved LDL-C concentration was approximately:
At day 84, an LDL-C concentration below 55 mg/dL was achieved by 51.0% of patients receiving obicetrapib, compared with 8.0% receiving placebo.
Obicetrapib also produced placebo-adjusted reductions in:
HDL-C increased by approximately 136 percentage points relative to placebo. (Orange County Research Center)
It is important to distinguish between the two commonly quoted BROADWAY figures:
Both figures are correct, but they describe different statistical comparisons.
BROOKLYN
BROOKLYN evaluated obicetrapib in 354 patients with heterozygous familial hypercholesterolaemia whose LDL-C remained elevated despite maximally tolerated lipid-lowering treatment.
At day 84, the placebo-adjusted LDL-C reduction was approximately:
36.3%
The LDL-C-lowering effect persisted during the one-year treatment period. At day 84, obicetrapib also produced placebo-adjusted changes of approximately:
These results suggest that obicetrapib may be particularly useful in patients with heterozygous familial hypercholesterolaemia who require substantial additional LDL-C reduction despite combination treatment. (Nature)
However, BROOKLYN was designed primarily to evaluate lipid changes and safety. It was not large enough to establish an effect on cardiovascular events.
TANDEM: obicetrapib plus ezetimibe
TANDEM was a randomised phase III trial involving 407 patients with established or high risk of atherosclerotic cardiovascular disease, heterozygous familial hypercholesterolaemia or statin intolerance.
Participants received one of four treatments for 84 days:
At day 84, the fixed-dose combination produced:
Obicetrapib monotherapy reduced LDL-C by approximately 31.9% compared with placebo.
The study therefore demonstrated that the two mechanisms are complementary:
The combination provides substantially greater LDL-C reduction than either individual component. (Amsterdam UMC)
No definitive outcome result yet
As of 30 July 2026, no completed, adequately powered cardiovascular outcomes trial has demonstrated that obicetrapib significantly reduces:
BROADWAY, BROOKLYN and TANDEM were primarily lipid-lowering and safety trials. Cardiovascular events were collected, but these studies were not designed or powered to provide definitive cardiovascular outcome conclusions.
Exploratory cardiovascular events in BROADWAY
During approximately one year of follow-up, the composite of:
occurred in:
Treatment | Event rate |
Obicetrapib | 4.2% |
Placebo | 5.2% |
This corresponded to:
The difference was not statistically significant. (Orange County Research Center)
The absolute numerical difference was one percentage point, corresponding to approximately ten fewer events per 1,000 patients over one year. However, because the confidence interval included no benefit and possible harm, it is not appropriate to calculate or present a reliable number needed to treat from these findings.
The result should therefore be interpreted as a potentially encouraging signal, not as proof that obicetrapib prevents cardiovascular events.
Cardiovascular death
A reduction in cardiovascular or coronary death has not been demonstrated. The number of deaths was small, and the trial was not powered to assess mortality.
Pooled analysis of BROADWAY and BROOKLYN
A prespecified or exploratory pooled analysis included 2,884 patients from BROADWAY and BROOKLYN.
The composite of coronary heart disease death, myocardial infarction, ischaemic stroke or coronary revascularisation occurred in:
The hazard ratio was 0.77, with a 95% confidence interval of 0.54–1.11 and a p value of 0.16. This result was not statistically significant.
A narrower composite of coronary heart disease death, myocardial infarction or coronary revascularisation occurred in:
The corresponding hazard ratio was 0.68, with a 95% confidence interval of 0.46–1.00 and a p value of 0.048. (JACC)
Although the latter finding narrowly reached conventional statistical significance, it remains exploratory because:
The pooled analysis should therefore be considered hypothesis-generating rather than definitive.
PREVAIL: the definitive cardiovascular outcomes trial
PREVAIL is the major phase III cardiovascular outcomes trial of obicetrapib.
It includes approximately 9,000 patients with established atherosclerotic cardiovascular disease whose LDL-C remains inadequately controlled despite maximally tolerated lipid-lowering therapy.
Participants are randomised to:
The primary composite endpoint comprises:
Secondary outcomes include all-cause mortality, total cardiovascular events, changes in LDL-C and apoB, and the development of new-onset diabetes.
The study is active but no longer recruiting, and completion of the primary follow-up is currently listed for late 2026. Only after PREVAIL has been completed and fully analysed will it be possible to determine reliably whether obicetrapib prevents cardiovascular events and how large any absolute benefit may be. (ClinicalTrials)
No overall superiority has been demonstrated
Obicetrapib has not been shown to be generally superior to established lipid-lowering treatments.
It is necessary to distinguish between:
There are currently no major direct outcome trials comparing obicetrapib head-to-head with ezetimibe, bempedoic acid, a PCSK9 antibody or inclisiran.
Approximate LDL-C-lowering potency
The effects observed in different clinical programmes can be broadly summarised as follows:
Treatment | Approximate additional LDL-C reduction |
Ezetimibe | 15–25% |
Bempedoic acid | 15–25% |
Obicetrapib | approximately 30–40% |
Obicetrapib plus ezetimibe | approximately 45–50% |
PCSK9 monoclonal antibodies | approximately 50–65% |
Inclisiran | approximately 45–55% |
These are indirect, cross-trial comparisons. The exact effect depends on baseline LDL-C, background treatment, adherence, study population and statistical method.
Obicetrapib monotherapy appears to provide greater average LDL-C reduction than ezetimibe or bempedoic acid alone, but generally less than injectable PCSK9 inhibition.
The fixed-dose combination of obicetrapib and ezetimibe approaches the magnitude of LDL-C reduction achieved with PCSK9-targeted treatments in some patients. However, this does not establish therapeutic equivalence or superiority.
For established alternatives, cardiovascular outcome benefits have already been demonstrated:
For obicetrapib, the definitive PREVAIL result remains pending.
Consequently, obicetrapib currently has less established cardiovascular outcome evidence than these treatments, even though it may produce greater LDL-C reduction than some of the oral alternatives.
Statins should remain the first-line treatment whenever they are effective and tolerated.
Obicetrapib may offer several clinically relevant advantages:
The oral fixed-dose combination could be particularly useful for patients who would otherwise require several tablets or who do not wish to use an injectable PCSK9-targeted treatment.
Lipoprotein(a)
Obicetrapib reduced lipoprotein(a), or Lp(a), by approximately:
This is a potentially relevant additional effect because elevated Lp(a) is an inherited, causal risk factor for atherosclerotic cardiovascular disease and calcific aortic-valve disease.
However, it remains uncertain whether the Lp(a) reduction produced by obicetrapib contributes independently to cardiovascular benefit. PREVAIL may provide additional information, but it is not a dedicated Lp(a)-lowering outcome trial. (Nature)
Most commonly reported adverse effects
The European CHMP summary lists the following as the most common adverse effects associated with Ubeslo:
These effects do not necessarily imply that each was substantially more frequent than with placebo. The detailed frequencies, severity categories and possible causal relationships will be set out in the final European product information after marketing authorisation.
Other complaints reported during clinical trials included:
Many of these events occurred at similar rates with placebo.
BROADWAY safety findings
In BROADWAY, at least one adverse event was reported by:
Laboratory abnormalities were uncommon:
Safety finding | Obicetrapib | Placebo |
Liver-enzyme abnormalities | 0.6% | 0.9% |
Muscle-enzyme abnormalities | 0.3% | 0.4% |
Worsening kidney function | 6.8% | 8.3% |
There was no apparent clinically relevant difference between the groups in:
This is important because the first CETP inhibitor to enter a large outcome trial, torcetrapib, increased blood pressure and aldosterone and was associated with increased cardiovascular morbidity and mortality. These effects were regarded as off-target properties of torcetrapib rather than inevitable consequences of CETP inhibition.
No comparable torcetrapib-like blood-pressure or aldosterone signal has been identified with obicetrapib in the completed phase III trials.
Nevertheless, the CHMP lists hypertension as one of the commonly reported adverse effects. Blood pressure should therefore be assessed as clinically appropriate, particularly after treatment initiation and in patients with poorly controlled hypertension.
Important limitations of the current safety evidence
Although the completed studies are reassuring, several limitations remain:
The long elimination half-life means that adverse effects may not resolve immediately after discontinuation.
Until the final European product information is available, specific claims about dose adjustment, use during pregnancy, severe organ impairment and clinically relevant drug interactions should be made cautiously.
The history of CETP inhibition has been difficult.
Torcetrapib
Torcetrapib increased HDL-C and reduced LDL-C but also increased blood pressure and aldosterone. Its cardiovascular outcome trial was stopped early because mortality and cardiovascular events were increased.
This was subsequently attributed largely to off-target toxicity rather than CETP inhibition itself.
Dalcetrapib
Dalcetrapib was a relatively weak CETP inhibitor. It substantially increased HDL-C but produced little LDL-C reduction and did not reduce cardiovascular events.
Evacetrapib
Evacetrapib produced marked HDL-C increases and moderate LDL-C lowering but did not reduce cardiovascular events during the relatively short outcome trial.
Anacetrapib
Anacetrapib reduced major coronary events by approximately 9% in the REVEAL trial. The benefit was broadly consistent with the modest reduction in non-HDL-C and was not attributed to the increase in HDL-C.
Anacetrapib was not commercialised, partly because it was highly lipophilic and accumulated in adipose tissue for several years.
Obicetrapib
Obicetrapib differs from these compounds because it is:
Nevertheless, the history of the CETP inhibitor class emphasises why cardiovascular benefit cannot be inferred solely from an increase in HDL-C or even from LDL-C lowering. PREVAIL remains essential.
Ubeslo
The CHMP has recommended Ubeslo as an adjunct to diet in adults with:
The proposed use includes:
The proposed indication concerns the treatment of elevated lipid levels. It does not yet contain a specific claim that obicetrapib prevents myocardial infarction, stroke or cardiovascular death.
Evlarco
Evlarco contains obicetrapib 10 mg and ezetimibe 10 mg in one tablet.
It is intended for adults with primary hypercholesterolaemia or mixed dyslipidaemia for whom the combination of obicetrapib and ezetimibe is clinically appropriate, including patients whose LDL-C remains above goal despite statin and ezetimibe treatment. (European Medicines Agency (EMA))
The precise approved positioning, switching instructions and use in statin-intolerant patients will be provided in the final Summary of Product Characteristics.
If approved, obicetrapib may be particularly relevant for adults with:
The choice between obicetrapib, ezetimibe, bempedoic acid, a PCSK9 antibody, inclisiran and other therapies should depend on:
Status as of 30 July 2026
Region | Regulatory status | Obicetrapib alone | Obicetrapib plus ezetimibe |
European Union | Positive CHMP opinion; final European Commission decision pending | Ubeslo® | Evlarco® |
United States | Not FDA-approved | No confirmed US brand name | No confirmed US brand name |
India | No confirmed CDSCO/DCGI marketing authorisation | No confirmed Indian brand name | No confirmed Indian brand name |
European Union
On 23 July 2026, the CHMP recommended marketing authorisation for:
The European Commission must issue the legally binding marketing-authorisation decision before the products can be marketed throughout the European Union.
The timing of availability in Germany and other individual European countries will also depend on manufacturing, launch decisions, pricing and national reimbursement procedures. (European Medicines Agency (EMA))
United States
Obicetrapib is not currently approved by the US Food and Drug Administration.
NewAmsterdam Pharma continues to describe it as an investigational product and has stated that the phase III programme is intended to support a New Drug Application. No official US trade name has been confirmed.
The European names Ubeslo and Evlarco should not automatically be assumed to be the future US brand names. (SEC)
India
No marketing authorisation for obicetrapib has been identified in the CDSCO lists of approved new drugs as of the stated date. There is consequently no confirmed Indian brand name.
The existence of patents or participation by Indian sites in clinical trials would not constitute marketing authorisation. (CDSCO)
Obicetrapib is a promising oral lipid-lowering treatment with several notable characteristics:
However, important uncertainties remain:
The most appropriate current conclusion is:
Obicetrapib is a potent oral LDL-C- and apoB-lowering treatment with encouraging exploratory cardiovascular signals. Its definitive role in cardiovascular prevention depends on the results of the PREVAIL cardiovascular outcomes trial.