European regulators have backed three new cholesterol-lowering therapies, potentially widening treatment options for patients who remain above low-density lipoprotein cholesterol (LDL-C) goals despite current therapy or cannot take statins. The Committee for Medicinal Products for Human Use (CHMP) recommended approval of Lyrokaul (lerodalcibep, LIB Therapeutics), Ubeslo (obicetrapib, A. Menarini International Licensing), and Evlarco (obicetrapib/ezetimibe, A. Menarini International Licensing). All three are intended as adjuncts to diet and may be used with statins or other lipid-lowering therapies, or without statins in selected patients.

The drugs differ in dosing and route: Lyrokaul is a once-monthly self-administered injection, while Evlarco and Ubeslo are both taken once daily as oral tablets. 

Lyrokaul 

Lyrokaul received a positive CHMP opinion for adults with primary hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH), or mixed dyslipidemia. It is indicated as an adjunct to diet in combination with a statin or a statin plus other lipid-lowering therapies in patients unable to reach LDL-C goals with the maximum tolerated statin dose, or alone or in combination with other lipid-lowering therapies in patients who are statin intolerant or for whom a statin is contraindicated.

Lyrokaul will be available as a 300-mg solution for injection in prefilled syringes that patients can self-administer once monthly. Its active substance, lerodalcibep, is a lipid-modifying agent that binds proprotein convertase subtilisin/kexin type 9 (PCSK9), preventing PCSK9-mediated degradation of LDL receptors in the liver. By increasing LDL receptor recycling and availability, it enhances clearance of LDL-C from the circulation.

Although the CHMP announcement does not specify the supporting trials, published phase 3 data for lerodalcibep include the LIBerate program, which enrolled over 2900 patients across studies comprising LIBerate-HeFH and LIBerate-HR. In LIBerate-HeFH, patients with HeFH on maximally tolerated statin therapy saw placebo-adjusted LDL-C reductions of roughly 59%-65% by week 24, with around two thirds reaching European Society of Cardiology-recommended targets. In the broader high-risk LIBerate-HR population, LDL-C fell by roughly 56% more than placebo over a year. The most common side effects include injection-site reactions.

If approved by the European Commission, Lyrokaul would add a monthly self-administered PCSK9-targeted option to the lipid-lowering armamentarium.

Ubeslo 

Ubeslo, an oral formulation of obicetrapib, also received a positive CHMP opinion for adults with primary hypercholesterolemia or mixed dyslipidemia. It is intended as an adjunct to diet in combination with a statin or a statin plus other lipid-lowering therapies in patients who do not achieve LDL-C goals with the maximum tolerated statin dose, or alone or in combination with other lipid-lowering therapies in patients who are statin intolerant or have a contraindication to statins.

Ubeslo will be available as a 10-mg film-coated tablet taken once daily. Obicetrapib is a cholesteryl ester transfer protein (CETP) inhibitor. CETP transfers cholesteryl esters from high-density lipoprotein (HDL) particles to atherogenic lipoproteins, including LDL. By blocking this pathway, obicetrapib lowers LDL-C through a mechanism distinct from statins and PCSK9 inhibitors.

The CHMP based its opinion on two 52-week trials: BROADWAY (n = 2530) and BROOKLYN (n = 354). Obicetrapib reduced LDL-C by 32.6 and 36.3 percentage points vs placebo, respectively, at day 84 in patients with atherosclerotic cardiovascular disease or HeFH (BROADWAY) or HeFH alone (BROOKLYN). Treatment also significantly improved apolipoprotein B, non-HDL-C, and lipoprotein(a), with a safety profile comparable to placebo. The most common side effects are hypertension, dizziness, headache, diarrhea, and abdominal pain.

Evlarco 

Evlarco combines obicetrapib with ezetimibe in a single fixed-dose product and received a positive CHMP opinion for adults with primary hypercholesterolemia or mixed dyslipidemia. The CHMP summary specifies three potential uses: in combination with a statin in patients unable to reach LDL-C goals despite the maximum tolerated statin dose plus ezetimibe; alone in patients who are statin intolerant or for whom a statin is contraindicated and who are unable to reach LDL-C goals with ezetimibe alone; or in patients already being treated with obicetrapib and ezetimibe as separate tablets, with or without a statin.

Evlarco will be available as a 10-mg/10-mg film-coated tablet. The two components offer complementary mechanisms: Obicetrapib lowers LDL-C through CETP inhibition, while ezetimibe blocks intestinal cholesterol absorption by inhibiting the NPC1L1 transporter.

The CHMP opinion drew on the phase 3 TANDEM trial, in which the fixed-dose combination produced an LDL-C reduction of roughly 49% vs placebo on top of maximally tolerated background therapy, with more than 70% of patients reaching an LDL-C target below 55 mg/dL. The most common side effects were hypertension, headache, dizziness, diarrhea and abdominal pain.

Next Steps 

A CHMP positive opinion is not a final approval: the European Commission typically converts these opinions into legally binding marketing authorizations valid across the EU within around 2 months, barring objection. Assuming that step proceeds as expected, clinicians should anticipate all three agents becoming available for prescribing later in 2026.