Berlin – A new study published in the New England Journal of Medicine offers promising results for individuals grappling with heterozygous familial hypercholesterolemia (HeFH), a common genetic condition leading to dangerously high cholesterol levels. The BROOKLYN trial, a randomized, double-blind, placebo-controlled clinical trial, demonstrates that the investigational drug obicetrapib, when added to standard-of-care treatment with statins, significantly reduces LDL-cholesterol – often referred to as “bad” cholesterol – and other lipid markers. This breakthrough could represent a significant advancement in managing a condition that substantially increases the risk of heart disease and stroke.
Familial hypercholesterolemia affects an estimated 1 in 250 people worldwide, making it one of the most prevalent inherited metabolic disorders. HeFH, in particular, arises from having one copy of a gene mutation causing impaired LDL receptor function. Even as statins remain the cornerstone of treatment, many patients don’t achieve adequate LDL-cholesterol lowering with statins alone, necessitating additional therapies. Obicetrapib, developed by NewAmsterdam Pharma, represents a novel approach, belonging to a class of drugs called MTP inhibitors. These medications perform by blocking the microsomal triglyceride transfer protein (MTP), which is crucial for the assembly of lipoproteins that carry cholesterol in the blood.
BROOKLYN Trial: Key Findings and Methodology
The BROOKLYN trial enrolled 399 patients with HeFH who were already receiving maximal tolerated doses of statins. Participants were randomly assigned in a 1:1 ratio to receive either 12 mg of obicetrapib daily or a placebo. The primary endpoint of the study was the percentage reduction in LDL-cholesterol from baseline to week 26. The results, presented at the American Heart Association Scientific Sessions in November 2023 and subsequently published, showed a remarkable 59% reduction in LDL-cholesterol in the obicetrapib group compared to a 7% increase in the placebo group. This difference was statistically significant (p < 0.001). The treatment group experienced significant reductions in non-HDL cholesterol, apolipoprotein B, and triglycerides.
Beyond LDL-cholesterol, the study also examined the impact of obicetrapib on other key lipid parameters. Non-HDL cholesterol, which includes all cholesterol-containing particles other than HDL, decreased by 44% in the obicetrapib group versus a 4% increase in the placebo group. Apolipoprotein B, a protein that is a component of LDL particles and a strong predictor of cardiovascular risk, was reduced by 48% with obicetrapib compared to a 3% increase with placebo. Triglycerides, another type of fat in the blood, were lowered by 26% in the treatment group, while remaining relatively stable in the placebo group. These comprehensive lipid improvements suggest a broad beneficial effect of obicetrapib on the overall lipid profile.
Safety and Tolerability
The safety profile of obicetrapib appeared to be manageable in the BROOKLYN trial. Serious adverse events were reported in 2.5% of patients in the obicetrapib group and 1.3% in the placebo group. The most common adverse events reported in the obicetrapib group were mild and included nausea, diarrhea, and abdominal pain. Notably, there were no reports of muscle-related side effects (myopathy), a common concern with some other cholesterol-lowering medications. But, it’s crucial to note that longer-term safety data are still needed to fully assess the potential risks associated with obicetrapib.
Implications for Patients with Heterozygous Familial Hypercholesterolemia
The findings from the BROOKLYN trial offer a new hope for patients with HeFH who struggle to reach their cholesterol goals with statins alone. Current guidelines recommend adding non-statin therapies, such as ezetimibe or PCSK9 inhibitors, for these patients. However, these options have limitations, including cost and the need for injections in the case of PCSK9 inhibitors. Obicetrapib, administered orally, could provide a more convenient and potentially more effective alternative. The drug’s mechanism of action, targeting MTP, differs from that of statins, ezetimibe, and PCSK9 inhibitors, offering a complementary approach to lipid management.
Dr. Robert Giugliano, the lead investigator of the BROOKLYN trial, stated in a press release that the results are “highly encouraging” and suggest that obicetrapib has the potential to “transform the treatment landscape for patients with HeFH.” CNBC reported on Trump’s recent request to pharmaceutical companies to lower drug prices, a separate but relevant issue impacting access to vital medications like those for hypercholesterolemia.
The Complex Landscape of Competing Interests
It is important to acknowledge the extensive list of potential competing interests disclosed regarding the researchers involved in the BROOKLYN trial. As detailed in the study’s disclosures, many investigators have received research funding, consulting fees, or stock options from NewAmsterdam Pharma, as well as other pharmaceutical companies involved in lipid-lowering therapies. While these relationships do not necessarily invalidate the study’s findings, they highlight the importance of transparency and critical evaluation of research data. The potential for bias should always be considered when interpreting clinical trial results, particularly in the pharmaceutical industry. The sheer breadth of these financial ties, involving numerous companies and various forms of compensation, underscores the complex financial web surrounding cardiovascular research.
Regulatory Pathway and Future Outlook
NewAmsterdam Pharma has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking approval for obicetrapib. The FDA is currently reviewing the application, and a decision is expected in the coming months. If approved, obicetrapib would represent a significant addition to the arsenal of therapies available for managing HeFH and reducing cardiovascular risk. Further research is planned to evaluate the long-term efficacy and safety of obicetrapib, as well as its potential benefits in other populations with high cholesterol, such as patients with atherosclerotic cardiovascular disease.
The development of obicetrapib also comes amidst growing scrutiny of drug pricing and access. BioSpace recently reported on former President Trump’s call for pharmaceutical companies to lower drug prices, a move that could potentially impact the cost of innovative medications like obicetrapib. Ensuring affordable access to these therapies will be crucial to maximizing their public health impact.
The BROOKLYN trial results mark a significant step forward in the treatment of heterozygous familial hypercholesterolemia. As the FDA review progresses, healthcare professionals and patients alike will be watching closely, hopeful that obicetrapib will soon become a valuable tool in the fight against cardiovascular disease. The next key milestone will be the FDA’s decision on the NDA, anticipated in the first half of 2026. We encourage readers to share their thoughts and experiences with HeFH in the comments below.