On 18 November, at the American Heart Association (AHA) 2024 Annual Scientific Sessions in Chicago, Illinois, US, during a late-breaking session on the topic of “New Targets and New Treatments: Advances in Lipid Therapeutics,” findings were presented from the Phase III clinical trial (NCT05425745) evaluating the safety and effectiveness of NewAmsterdam Pharma’s obicetrapib as an adjunct to maximally tolerated lipid-modifying therapies, in patients with heterozygous familial hypercholesterolemia (HeFH).
Obicetrapib is a selective inhibitor of cholesteryl ester transfer protein (CETP). By blocking CETP, these inhibitors work to increase high-density lipoprotein (HDL) cholesterol and lower triglyceride levels by preventing the transfer of cholesteryl esters from HDL to ApoB-containing lipoproteins. Additionally, CETP inhibitors have been shown to lower Lp(a) levels by inhibiting the transfer of cholesteryl esters to apo(a)-containing lipoproteins, which in turn reduces the formation of Lp(a) particles in the blood.
Go deeper with GlobalData
Professor Stephen Nicholls, director at the Victorian Heart Hospital and Victorian Heart Institute, presented the results of the Phase III BROOKLYN trial, which achieved its primary endpoint. Patients were randomly assigned in a 2:1 ratio to receive either obicetrapib 10mg or a matching placebo, orally, once daily for 52 weeks.
Nicholls presented the study results, highlighting percentage changes in low-density lipoprotein (LDL) cholesterol with obicetrapib over the study’s duration, which demonstrated significant reductions. Placebo-adjusted LDL cholesterol decreased by 36.3% at day 84 and 41.5% at day 365. Additionally, 34% of patients treated with obicetrapib achieved LDL cholesterol reductions greater than 50%. When assessing the attainment of treatment goals, Nicholls explained that 77% of patients reached the primary prevention target for familial hypercholesterolemia (FH) of 100mg/dL, 51% achieved the 70mg/dL target, and nearly 25% of patients met the target of 55mg/dL for very high-risk FH patients. Regarding other lipid parameters, placebo-adjusted reductions were observed in non-HDL cholesterol by up to 37.5%, and apoB decreased by 25.8%. As expected, CETP inhibitors raise HDL cholesterol; with obicetrapib, placebo-adjusted HDL cholesterol increased by up to 138.7%, while triglycerides showed a modest placebo-adjusted reduction of 11.7%. Obicetrapib led to a placebo-adjusted reduction in Lp(a) of 54.3%, independent of its effects on lowering atherogenic lipid levels and increasing HDL cholesterol. For the first time, nuclear magnetic resonance (NMR) analysis was used to assess lipid particles in patients treated with obicetrapib. At day 180, a 52.5% reduction in total LDL particle concentration was observed, along with a placebo-adjusted reduction of 102.3% in small atherogenic LDL particles. Furthermore, a placebo-adjusted reduction in Lp(a) of up to 54.3% was observed at day 365 in patients treated with obicetrapib, with 38% achieving a greater than 50% reduction.
Nicholls noted obicetrapib was well tolerated, with no serious adverse events or clinically significant changes in vital signs, electrocardiograms, or other laboratory values reported. He also mentioned that while previous CETP inhibitors have been associated with elevated blood pressure, no changes in diastolic or systolic blood pressure were observed with obicetrapib throughout the study. Nicholls acknowledged some limitations of the study, including the fact that it evaluated the effect of obicetrapib for 365 days, and the impact of longer treatment durations requires further investigation. Additionally, Lp(a) lowering was observed in a cohort that was not specifically required to have elevated Lp(a) levels at study entry. Future studies will focus on evaluating the impact of obicetrapib in individuals with elevated Lp(a) levels. Finally, whether treatment with obicetrapib leads to a reduction in cardiovascular events remains to be determined.
Key opinion leaders (KOLs) interviewed by GlobalData have emphasised the significant unmet need for therapies that target Lp(a) in dyslipidemia, as elevated Lp(a) levels are a known risk factor for cardiovascular diseases such as heart attacks and strokes. Currently, there are no therapies available on the market that directly target Lp(a). Standard dyslipidemia treatments, such as statins and other cholesterol-lowering medications, are not effective in reducing Lp(a) levels. As a result, many patients with high Lp(a) levels continue to face an increased risk of cardiovascular events, even when other lipid levels are controlled. This highlights the growing need for therapies that can effectively lower Lp(a). According to GlobalData, NewAmsterdam’s therapy shows promise in filling this gap, potentially providing a significant advancement in managing dyslipidemia and reducing cardiovascular risk. The longer-term effect of obicetrapib on cardiovascular outcomes is currently being evaluated in the PREVAIL trial. GlobalData’s report ‘Dyslipidemia: Seven-Market Drug Forecast and Market Analysis‘ forecasts that obicetrapib will generate the highest sales among pipeline drugs across the seven major markets (7MM: US, France, Germany, Italy, Spain, UK, and Japan), with projected sales reaching $1.40bn by 2032.
How well do you really know your competitors?
Access the most comprehensive Company Profiles on the market, powered by GlobalData. Save hours of research. Gain competitive edge.
Thank you!
Your download email will arrive shortly
Not ready to buy yet? Download a free sample
We are confident about the unique quality of our Company Profiles. However, we want you to make the most beneficial decision for your business, so we offer a free sample that you can download by submitting the below form
By GlobalData
