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AHA 24: BROOKLYN: Safety and Efficacy of Obicetrapib in Patients with HeFH

Published: 28 Nov 2024

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AHA Conference 2024 -  BROOKLYN: Safety and efficacy outcomes of obicetrapib (NewAmsterdam Pharma) alongside lipid-lowering therapy in Heterozygous Familial Hypercholesterolemia (HeFH) management.

Dr Stephen Nicholls (Monash University and The Victorian Heart Hospital, Melbourne, AU) joins us onsite at AHA Conference to discuss the findings from BROOKLYN (NCT05425745).

BROOKLYN is a phase 3, randomized, placebo-controlled trial investigating the use of obicetrapib in patients with HeFH who have undergone at least eight weeks of maximally tolerated lipid modifying therapy prior to screening. 354 patients were enrolled in the trial and were followed-up after the 365-day treatment period. The primary outcome measure was the percent change from baseline to day 84 in low density lipoprotein-cholesterol.

Interview Questions:
1.    What is the reasoning behind the trial and the current unmet needs in HeFH management?
2.    Could you tell us about the mechanism of action behind obicetrapib?
3.    What was the study design and patient population?
4.    What were the key findings?
5.    What further research is needed in this area?

Recorded on-site at AHA Conference in Chicago, 2024.

Editors: Yazmin Sadik, Jordan Rance.
Videographers: Mike Knight, Dan Brent, Oliver Miles, Tom Green, David Ben-Harosh.

Support: This is an independent interview produced by Radcliffe Cardiology.

Transcript

My name's Steve Nicholls, I'm professor of cardiology at Monash University and the director of the Victorian Heart Hospital.

What is the reasoning behind the trial and the current unmet needs in HeFH management?

So BROOKLYN is looking at the CETP inhibitor, obicetrapib. CETP inhibitors have been a very significant area of interest now for several decades, originally because of the idea that they might raise HDL cholesterol and that might be a good thing.

The kind of the whole field has turned to more focus on their ability to lower LDL cholesterol. And so BROOKLYN is a study of looking at the effects of obicetrapib in patients with FH. We know that they have high levels of cholesterol, a preventable form of cardiovascular risk, but we also know that many patients with FH don't get to goal despite pretty good treatment. And so that's what we wanted to test here was would giving obicetrapib to those patients achieve better LDL cholesterol lowering and get more people to goal.

Could you tell us about the mechanism of action behind obicetrapib?

Obicetrapib inhibits a factor called CETP or cholesterol ester transfer protein. That's a factor that's really important in shuffling different lipid factors amongst lipoproteins. We know that if you block CETP, you'll raise HDL cholesterol, but with the more potent CETP inhibitors you'll lower LDL cholesterol and also lower LP(a). So there's potentially a range of benefits, particularly in terms of reducing the levels of those atherogenic lipid parameters.

What was the study design and patient population?

So BROOKLYN's a phase 3 study. 354 patients with FH, they had to be high cardiovascular risk, they had to have on stable, good lipid lowering therapy and they were randomized in a 2:1 fashion to treatment with obicetrapib 10mg or placebo for 52 weeks.

What were the key findings?

Key findings was up to a 41.5% lowering of LDL cholesterol with obicetrapib on top of statins, ezetimibe in 50% of patients, PCSK9 inhibitors are 20% of patients – so really good treated patients. We get an extra 40% lowering of LDL cholesterol. 77% of patients get to a primary prevention LDL cholesterol target of 100 mg/dL or 2.6 mmol/L. 51% of patients get below 70 mg/dL or 1.8 mmol/L. We saw significant reductions in triglycerides, non-HDL cholesterol. We saw an up to 54% reduction in levels of LP(a), and we saw really good safety and tolerability.

What further research is needed in this area?

So BROOKLYN helps us in two ways. First of all, from an FH perspective, it shows that there are other therapies coming which can get many more FH patients to go. So stay tuned from that perspective. From an obicetrapib CETP perspective, what it tells us is it gives us more information about the lipid effects of this drug.

That's going to be really important as we now really move forward into a large cardiovascular outcome trial, which is currently underway – 9,000 patients fully enrolled. And the question will be, will that type of degree of lipid lowering in terms of 40 plus percent lowering of LDL, 50 plus percent lowering of LP(a), lowering triglycerides, non-HDL cholesterol, will that translate to a reduction in cardiovascular risk? We hope that's that case, but we'll have to wait for the outcome trial to finish.

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