Regulatory & Policy

Menarini, NewAmsterdam win EU approval for first CETP inhibitor in hypercholesterolemia

Menarini, NewAmsterdam win EU approval for first CETP inhibitor in hypercholesterolemia

The European Commission has granted marketing authorization for obicetrapib as both a monotherapy (Ubeslo) and a fixed-dose combination with ezetimibe (Evlarco), giving European patients with primary hypercholesterolemia — including heterozygous familial hypercholesterolemia and mixed dyslipidemia — access to an oral, once-daily cholesteryl ester transfer protein (CETP) inhibitor, a mechanism that had not previously reached regulatory approval anywhere in the world. The decision, which converts the positive CHMP opinion issued in July 2026 into a full marketing authorization, positions obicetrapib as an oral alternative for patients who remain above low-density lipoprotein cholesterol (LDL-C) targets despite existing therapies.

The authorization covers obicetrapib 10 mg monotherapy and a fixed-dose combination of 10 mg obicetrapib plus 10 mg ezetimibe. Netherlands-based NewAmsterdam Pharma Company N.V. (Nasdaq: NAMS) developed the compound; Italy-based Menarini Group holds exclusive commercialization rights in Europe and will lead the regional launch. Under their licensing agreement, NewAmsterdam is entitled to tiered double-digit percentage royalties — ranging from the low double-digits to the mid-twenties on net sales in the Menarini territory — and up to an additional EUR 833 million upon achievement of specified clinical, regulatory, and commercial milestones.

The approval rests on data from three Phase III trials: BROADWAY, BROOKLYN, and TANDEM. Across these studies, obicetrapib monotherapy reduced LDL-C by up to 40% versus placebo according to NewAmsterdam, while the combination with ezetimibe produced reductions of approximately 50% versus placebo. In each trial, the tolerability profile was reported as comparable to placebo.

Obicetrapib inhibits CETP, a plasma protein that transfers cholesterol esters from high-density lipoprotein to LDL particles. Earlier CETP inhibitors — including torcetrapib, dalcetrapib, and anacetrapib — failed in late-stage development due to off-target cardiovascular harm or insufficient efficacy. NewAmsterdam has argued that obicetrapib's low dose and selectivity differentiate it from those predecessors, though whether the LDL reductions translate into reduced cardiovascular events remains under investigation.

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The competitive landscape for LDL lowering in patients who are statin-intolerant or inadequately controlled includes injectable PCSK9 inhibitors such as evolocumab and alirocumab, the small interfering RNA (siRNA) inclisiran administered by subcutaneous injection twice yearly, and the small-molecule PCSK9 inhibitor class. Obicetrapib is oral and once-daily, a convenience profile that distinguishes it from injectable options, though its cardiovascular outcomes data are not yet available.

That question is being addressed in PREVAIL, an ongoing Phase III cardiovascular outcomes trial that completed enrollment of more than 9,500 patients in April 2024. Two additional Phase III trials, REMBRANDT and RUBENS, are also ongoing, the companies said. Outcomes data from PREVAIL will be critical to establishing obicetrapib's place in treatment guidelines and informing payer negotiations across European markets.


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