NewAmsterdam’s Obicetrapib Gets Positive CHMP Opinion for Cholesterol Treatment in Europe

Ubeslo and Evlarco move closer to potential approval for patients with high LDL-C

NewAmsterdam Pharma, together with its partner Menarini Group, announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending marketing authorization for two obicetrapib-based treatments.

The products are Ubeslo, which contains 10 mg of obicetrapib as a monotherapy, and Evlarco, a fixed-dose combination containing 10 mg of obicetrapib and 10 mg of ezetimibe.

The treatments are being developed for patients with primary hypercholesterolemia, including people with heterozygous familial hypercholesterolemia (HeFH) and those with non-familial or mixed dyslipidemia.

The CHMP opinion is an important regulatory milestone, but the products still need a final decision from the European Commission before they can receive centralized marketing authorization across the European Union and certain other European countries.

Final European decision is still pending

The positive CHMP opinion will now be reviewed by the European Commission.

The European Commission has the authority to grant a centralized marketing authorization that would be valid across all EU member states, as well as Iceland, Liechtenstein and Norway.

The final decision is expected later this year.

If the European Commission approves the treatments, Menarini will be responsible for marketing obicetrapib in Europe under its agreement with NewAmsterdam.

Obicetrapib is designed to lower LDL-C

Obicetrapib is a low-dose oral cholesteryl ester transfer protein (CETP) inhibitor.

NewAmsterdam is developing the medicine as an alternative or complementary approach for patients who continue to have elevated LDL-C despite existing treatment options or who do not tolerate currently available therapies well.

LDL-C, often referred to as "bad cholesterol," is an important risk factor for cardiovascular disease.

Obicetrapib is designed to be taken once daily and can be administered with or without food.

According to NewAmsterdam, the treatment could provide another option for patients who are not reaching their recommended LDL-C targets with existing therapies.

Ubeslo and Evlarco show LDL-C reductions in Phase 3 trials

The CHMP's positive opinion was supported by data from NewAmsterdam's clinical development programme.

This included results from the Phase 3 BROADWAY, BROOKLYN and TANDEM trials.

In these studies, obicetrapib monotherapy produced statistically significant LDL-C reductions of up to 40% compared with placebo.

The combination of obicetrapib and ezetimibe produced approximately 50% LDL-C reductions compared with placebo.

NewAmsterdam also reported that the treatments showed a tolerability profile comparable to placebo.

These results helped support the regulatory application for Ubeslo and Evlarco in Europe.

NewAmsterdam continues to study cardiovascular outcomes

The company's development programme for obicetrapib is continuing beyond LDL-C reduction.

One of the major ongoing studies is PREVAIL, a Phase 3 cardiovascular outcomes trial designed to evaluate whether obicetrapib can reduce major adverse cardiovascular events, also known as MACE.

The company began the PREVAIL trial in March 2022 and completed recruitment in April 2024.

More than 9,500 patients were randomized into the study.

NewAmsterdam and Menarini are also advancing other Phase 3 programmes, including REMBRANDT and RUBENS.

The results from these studies will add more information about the potential role of obicetrapib in managing cardiovascular risk.

Why lowering LDL-C remains a major challenge

Cardiovascular disease remains the leading cause of death worldwide.

Although statins and other lipid-lowering therapies are widely available, many patients still do not reach their recommended LDL-C targets.

This is especially important for people who already have a high risk of cardiovascular disease.

In the US, NewAmsterdam estimates that around 30 million adults who are considered undertreated are not reaching their risk-based LDL-C targets. This includes approximately 13 million people with atherosclerotic cardiovascular disease (ASCVD).

Among patients with ASCVD, fewer than one in four reach an LDL-C level below 70 mg/dL.

For very high-risk ASCVD patients, only around 10% reach the target of below 55 mg/dL.

This means that even with millions of lipid-lowering prescriptions being issued, a significant number of patients still need better or more convenient treatment options.

Cardiovascular risk involves more than LDL-C

High LDL-C is an important factor in cardiovascular disease, but it is not the only one.

Other factors can also increase cardiovascular risk.

These include lifestyle habits, smoking, obesity, inflammation, thrombosis, high triglyceride levels, elevated lipoprotein(a), and type 2 diabetes.

Because of this, doctors and researchers are increasingly looking at ways to manage cardiovascular risk beyond a single cholesterol measurement.

NewAmsterdam says its goal is to develop treatments that not only lower LDL-C but also help address the wider issue of residual cardiovascular risk.

NewAmsterdam calls the CHMP opinion a major milestone

Dr. Michael Davidson, chief executive officer of NewAmsterdam Pharma, said the positive CHMP opinion represents an important step for both the company and patients who are unable to reach their LDL-C targets with existing therapies.

He highlighted obicetrapib's once-daily oral administration and the company's clinical data showing significant LDL-C reductions.

The company now expects to work toward the European Commission's final regulatory decision.

Menarini CEO Elcin Barker Ergun also welcomed the CHMP opinion and said the company hopes to make obicetrapib available to European patients who are not achieving their LDL-C goals with current treatments, subject to final approval.

Menarini will handle European commercialization

NewAmsterdam and Menarini have an exclusive licensing agreement covering obicetrapib in Europe.

Menarini holds the exclusive marketing rights for obicetrapib in the region, both as a monotherapy and as part of the fixed-dose combination with ezetimibe.

The company will also work with regulatory authorities and manage marketing activities across Europe.

Under the agreement, NewAmsterdam is eligible to receive tiered royalties on net sales in the Menarini territory.

The company could also receive up to €833 million in additional payments if agreed clinical, regulatory and commercial milestones are achieved.

What are Ubeslo and Evlarco?

Ubeslo is the proposed brand name for obicetrapib 10 mg used as a monotherapy.

Evlarco is the proposed brand name for the fixed-dose combination of 10 mg obicetrapib and 10 mg ezetimibe.

Ezetimibe is an established cholesterol-lowering medicine that works by reducing the absorption of cholesterol in the intestine.

By combining the two medicines into a single fixed-dose treatment, NewAmsterdam is aiming to provide another oral option for patients who need additional LDL-C lowering.

The European regulatory application covers patients with primary hypercholesterolemia, including those with HeFH and those with non-familial or mixed dyslipidemia.

Obicetrapib development started with Phase 2 studies

NewAmsterdam has evaluated obicetrapib across several Phase 2 trials, including ROSE2, TULIP, ROSE and OCEAN.

The company has also studied the medicine in Phase 3 trials such as BROADWAY, BROOKLYN and TANDEM.

Across these programmes, NewAmsterdam has reported statistically significant LDL-C reductions with a side effect profile similar to placebo.

The company is now continuing the development programme to determine whether these LDL-C reductions can translate into meaningful cardiovascular benefits.

The upcoming cardiovascular outcomes data from PREVAIL will therefore be closely watched as the company moves forward with the broader development of obicetrapib.

NewAmsterdam and Menarini prepare for the next regulatory step

The CHMP recommendation moves Ubeslo and Evlarco closer to potential availability for patients in Europe.

The European Commission's final decision will determine whether the products receive centralized marketing authorization.

At the same time, NewAmsterdam continues to evaluate obicetrapib in ongoing Phase 3 clinical studies, with the broader programme focused on LDL-C reduction and cardiovascular outcomes.