In July 2026, the European Medicines Agency recommended Lyrokaul® (lerodalcibep) for the treatment of patients with hypercholesterolaemia and mixed dyslipidaemia.
The full proposed indication is as follows:
Lyrokaul is indicated as an adjunct to diet for the treatment of adults with primary hypercholesterolaemia, including heterozygous familial and non-familial hypercholesterolaemia, or mixed dyslipidaemia:
Lyrokaul is available as a 300 mg solution for injection in a pre-filled syringe.
Lerodalcibep binds to proprotein convertase subtilisin/kexin type 9, or PCSK9. PCSK9 normally binds to LDL receptors on the surface of liver cells. When a PCSK9–LDL-receptor complex is taken up into the liver cell, the LDL receptor is degraded rather than recycled to the cell surface. Consequently, fewer LDL receptors are available to remove LDL particles from the bloodstream.
When PCSK9 is inhibited, fewer LDL receptors are degraded. More LDL receptors therefore return to the liver-cell surface, where they can remove additional LDL from the blood. This results in a marked reduction in circulating LDL-C.The PCSK9 monoclonal antibodies evolocumab and alirocumab lower LDL-C according to the same fundamental principle.
This image was created using artificial intelligence.
Lyrokaul® is the European brand name for lerodalcibep, an injectable PCSK9 inhibitor. The active substance is not a conventional monoclonal antibody. It is a small PCSK9-binding protein fused to human serum albumin to extend its duration of action. It is administered once monthly by subcutaneous injection.
In the large phase III LIBERATE-HR trial involving 922 patients, lerodalcibep produced the following additional LDL-C reductions on top of existing lipid-lowering treatment:
In a particularly strict intention-to-treat analysis, in which treatment discontinuations were statistically treated as a loss of efficacy, the LDL-C reduction was approximately 49.7–55.3%.
As a practical summary, lerodalcibep may therefore be expected to produce an additional LDL-C reduction of approximately 50–60%.
In patients with heterozygous familial hypercholesterolaemia, the effect was similarly pronounced:
Example
In a patient with a baseline LDL-C concentration of 120 mg/dL, a reduction of 55% would theoretically result in an LDL-C concentration of approximately 54 mg/dL.
However, the individual response may be either smaller or greater.
The following results were obtained after 52 weeks in the LIBERATE-HR trial and are corrected for changes observed with placebo:
Lipid parameter | Change with lerodalcibep |
LDL-C | Approximately −50% to −60% |
Non-HDL-C | −47.3% |
Apolipoprotein B | −42.9% |
VLDL-C | −25.9% |
Lipoprotein(a) | Median reduction of approximately 30% |
Triglycerides | Median reduction of approximately 14% |
Total cholesterol | −32.9% |
HDL-C | +6.5% |
Clinical Significance of These Changes
The reduction in apolipoprotein B of approximately 43% indicates that lerodalcibep not only reduces the amount of cholesterol carried within LDL particles but also substantially reduces the number of circulating atherogenic lipoprotein particles.
Non-HDL-C includes cholesterol carried by LDL, VLDL, remnant particles and other apolipoprotein B-containing particles.
Its reduction of approximately 47% confirms that lerodalcibep has a broad effect on atherogenic lipoproteins.
The approximately 30% reduction in lipoprotein(a), or Lp(a), may represent an additional potential benefit.
However, lerodalcibep is not a specifically targeted Lp(a)-lowering medicine. It has not yet been demonstrated that this reduction independently prevents cardiovascular events beyond the effect achieved through LDL-C lowering.
The reduction in triglycerides is moderate. Lyrokaul should therefore not be considered a primary treatment for severe hypertriglyceridaemia.
The small increase in HDL-C is probably of less clinical importance than the substantial reductions in LDL-C, non-HDL-C and apolipoprotein B.
No Definitive Cardiovascular Outcomes Trial
As of 30 July 2026, no completed, sufficiently large trial specifically designed to assess cardiovascular events has been reported for lerodalcibep.
The completed phase III trials primarily evaluated:
The authors of the LIBERATE-HR trial explicitly stated that larger and longer studies would be required to assess the effects of lerodalcibep on cardiovascular morbidity and mortality.
Exploratory Pooled Cardiovascular Event Analysis
A prospectively planned but exploratory pooled analysis of the three phase III trials LIBERATE-HR, LIBERATE-CVD and LIBERATE-HeFH has been presented.
The combined endpoint included:
Results After 24 Weeks
Treatment | Cardiovascular events |
Lerodalcibep | 11 of approximately 1,550 patients: 0.7% |
Placebo | 13 of approximately 768 patients: 1.7% |
This represented an approximate relative reduction of 58% and an absolute difference of approximately 1.0 percentage point.
Results After 52 Weeks
Treatment | Cardiovascular events |
Lerodalcibep | 27 events: 2.2% |
Placebo | 25 events: 4.1% |
This represented an approximate relative reduction of 47% and an absolute difference of approximately 1.9 percentage points.
How Reliable Are These Findings?
The results are encouraging but do not yet represent definitive proof of cardiovascular efficacy:
It would therefore be inappropriate to state that Lyrokaul has been proven to reduce mortality by 47% or 58%.
A scientifically accurate formulation would be:
In an exploratory pooled analysis, fewer combined cardiovascular events were observed with lerodalcibep than with placebo. However, a definitive reduction in myocardial infarction, stroke or cardiovascular death must still be confirmed in a sufficiently large, dedicated cardiovascular outcomes trial.
Lyrokaul, or lerodalcibep:
Its LDL-C-lowering effect is broadly similar in magnitude to that of the established PCSK9 monoclonal antibodies evolocumab and alirocumab.
However, the positive cardiovascular outcome results obtained with evolocumab and alirocumab cannot automatically be extrapolated to lerodalcibep.
Lyrokaul® contains lerodalcibep, a long-acting PCSK9 inhibitor. In the United States, the same active substance is marketed under the brand name Lerochol®.
The proposed European dosage and the dosage already approved in the United States are:
Lerodalcibep 300 mg once monthly by subcutaneous injection.
Each pre-filled syringe contains 300 mg in 1.2 mL of solution.
The injection is administered subcutaneously into:
After appropriate instruction, patients may administer the monthly injection themselves.
The injection site should be rotated with each administration. The medicine should not be injected into skin that is red, hardened, tender, bruised, damaged or otherwise affected.
A refrigerated pre-filled syringe should be allowed to reach room temperature for at least 30 minutes before administration.
What Should Be Done If a Dose Is Missed?
According to the US prescribing information:
These specific recommendations are taken from the US prescribing information for Lerochol. The final European product information for Lyrokaul may differ in certain details.
The most characteristic adverse effects are injection-site reactions.
These may include:
The following adverse effects were reported in the pooled 52-week trials:
Adverse effect | Lerodalcibep | Placebo |
Nasopharyngitis or common-cold symptoms | 15% | 14% |
Injection-site reactions | 12% | 5% |
Peripheral oedema | 2% | Less than 1% |
In the 24-week trial involving patients with heterozygous familial hypercholesterolaemia, injection-site reactions occurred in 18% of patients receiving lerodalcibep and 3% of patients receiving placebo.
Other reported adverse effects included:
Adverse effect | Lerodalcibep | Placebo |
Diarrhoea | 3% | 1% |
Nausea | 2% | 0% |
Peripheral oedema | 2% | Less than 1% |
Treatment Discontinuations and Serious Adverse Events
In the two 52-week studies, approximately 4% of patients in both the lerodalcibep and placebo groups discontinued treatment because of adverse events.
Injection-site reactions resulted in treatment discontinuation in approximately 1% of patients receiving lerodalcibep.
The overall frequency of serious adverse events was similar in the lerodalcibep and placebo groups.
Antibodies Against Lerodalcibep
Antibodies against the medicine were detected in some patients.
In the studies evaluated to date, these antibodies did not have a clinically meaningful effect on LDL-C reduction, overall efficacy or safety.
Pregnancy and Impaired Organ Function
According to the US prescribing information, lerodalcibep should generally be discontinued if pregnancy occurs, as adequate data from pregnant women are not available.
No clinically relevant pharmacokinetic differences were identified in patients with mild or moderate renal or hepatic impairment.
However, insufficient information is available regarding patients with severe renal impairment or severe hepatic impairment.
Status as of 30 July 2026
Region | Regulatory status | Brand name |
European Union | Positive CHMP opinion; final European Commission decision pending | Lyrokaul® |
United States | FDA-approved since 12 December 2025; commercially available since May 2026 | Lerochol® |
India | No confirmed marketing authorisation; a clinical trial has been authorised | No confirmed brand name |
European Union
On 23 July 2026, the Committee for Medicinal Products for Human Use, or CHMP, issued a positive opinion recommending the approval of Lyrokaul.
It is intended for adults with:
Lyrokaul is intended to be used as an adjunct to diet, either alone or in combination with other lipid-lowering treatments.
It is presented as a 300 mg solution for injection in a pre-filled syringe and is intended for monthly self-administration after appropriate training.
As of 30 July 2026, the legally binding marketing-authorisation decision by the European Commission was still pending.
United States
The US Food and Drug Administration approved lerodalcibep-liga under the brand name Lerochol® on 12 December 2025.
It is indicated as an adjunct to diet and exercise to reduce LDL-C in adults with hypercholesterolaemia, including heterozygous familial hypercholesterolaemia.
The US commercial launch took place in May 2026.
The US authorisation does not currently include a specific indication for the prevention of myocardial infarction, stroke or cardiovascular death. It is an indication for the reduction of LDL cholesterol.
India
No regular marketing authorisation or official brand name has been documented for lerodalcibep in India.
On 9 June 2026, the Indian Central Drugs Standard Control Organisation authorised the conduct of a phase IIIb clinical trial of lerodalcibep.
Authorisation to conduct a clinical trial is not equivalent to authorisation to manufacture, import, market or routinely prescribe the medicine.
Summary of Regulatory Status
Lerodalcibep is already available in the United States under the brand name Lerochol®.
In Europe, Lyrokaul® has received a positive CHMP opinion, but final approval by the European Commission was still pending as of 30 July 2026.
No regular marketing authorisation has yet been documented in India.
status as of 30 July 2026.
The literature covers the mechanism of action, monthly administration, LDL-C reduction, effects on other lipid fractions, adverse effects, cardiovascular events and regulatory status.
Major Phase III Trials
Principal source for: the monthly 300 mg dosage, reductions in LDL-C, non-HDL-C, apolipoprotein B, lipoprotein(a) and triglycerides, changes in HDL-C, and safety over 52 weeks.
Principal source for: efficacy in heterozygous familial hypercholesterolaemia and LDL-C reductions of approximately 59–65%.
Source for: long-term efficacy and safety in patients with established atherosclerotic cardiovascular disease. This publication is available as a congress abstract.
Source for: the pooled analysis of safety and efficacy from three major phase III trials. Adverse-event rates were generally comparable with placebo, apart from a higher incidence of predominantly mild injection-site reactions.
Effects on LDL-C and Other Lipid Fractions
These results are supported by Reference 1. Depending on the statistical analysis used, the additional LDL-C reduction was approximately 50–63%.
Cardiovascular Events and Mortality
Source for: the exploratory pooled cardiovascular event analysis from LIBERATE-HR, LIBERATE-CVD and LIBERATE-HeFH. The analysis showed an encouraging event signal but was not a dedicated, adequately powered cardiovascular outcomes trial.
The authors explicitly state that larger and longer trials are required to determine the effects of lerodalcibep on cardiovascular morbidity and mortality.
The currently available evidence therefore does not definitively establish that lerodalcibep reduces myocardial infarction, stroke, cardiovascular death or all-cause mortality. The pooled event analysis should be considered hypothesis-generating.
Comparative Outcome Trials of Established PCSK9 Inhibitors
FOURIER: evidence that evolocumab reduces cardiovascular events.
ODYSSEY OUTCOMES: evidence that alirocumab reduces cardiovascular events.
These studies are relevant because the positive cardiovascular outcome findings obtained with evolocumab and alirocumab cannot automatically be extrapolated to lerodalcibep.
US Prescribing Information: Administration and Adverse Effects
The prescribing information supports the following information:
Source for: the FDA assessment of the pivotal trials involving more than 2,300 participants and a summary of the benefits and risks.
Source for: the US approval date, the name of the active substance and the approved indication for LDL-C reduction in adults with hypercholesterolaemia, including heterozygous familial hypercholesterolaemia.
Source for: formal FDA approval, the brand name Lerochol® and the dosage form as a pre-filled syringe containing 300 mg/1.2 mL.
European Regulatory Status
The EMA source supports the following information:
Source for: confirmation that Lyrokaul was recommended for approval as a once-monthly, self-administered injection.
Regulatory Status in India
This document supports only the recommendation to authorise a phase IIIb clinical trial of lerodalcibep in India. Such clinical-trial authorisation is not a marketing authorisation.
Lerodalcibep was not listed in the available Indian regulatory documents as an active substance authorised for manufacture, import or marketing as of the stated date. No confirmed Indian brand name was therefore documented.
This conclusion is based on the official CDSCO approval lists and the separately documented clinical-trial authorisation.
No results from a dedicated, adequately powered cardiovascular outcomes trial are currently available for lerodalcibep. A pooled exploratory analysis showed fewer combined cardiovascular events but does not yet permit a definitive conclusion regarding myocardial infarction, stroke, cardiovascular death or all-cause mortality.