NewAmsterdam Pharma Company N.V. announced that the European Medicines Agency (EMA) has validated Marketing Authorization Applications for obicetrapib 10 mg monotherapy and a 10 mg obicetrapib plus 10 mg ezetimibe fixed-dose combination for patients with primary hypercholesterolemia and mixed dyslipidemia. The applications were submitted by NewAmsterdam's partner, A. Menarini International Licensing S.A., who holds exclusive commercialization rights across Europe.
The EMA validation allows for regulatory review of NewAmsterdam's pivotal Phase 3 clinical program, which demonstrated substantial LDL-cholesterol lowering capabilities across multiple patient populations. "This marks a significant step forward in our mission to deliver a novel, first in class therapeutic option to add to statin therapy to further reduce LDL-C for millions of patients not reaching their LDL-C goals," said Michael Davidson, M.D., Chief Executive Officer of NewAmsterdam.
Phase 3 Clinical Program Demonstrates Strong Efficacy
The regulatory submission is supported by data from three Phase 3 trials: BROADWAY, BROOKLYN, and TANDEM, which collectively showed 35-40% LDL-C lowering with obicetrapib monotherapy versus placebo and approximately 50% LDL-C lowering when combined with ezetimibe.
The BROADWAY trial evaluated obicetrapib in 2,530 adult patients with established atherosclerotic cardiovascular disease and/or heterozygous familial hypercholesterolemia whose LDL-C remained inadequately controlled despite maximally tolerated lipid-lowering therapy. The primary endpoint was achieved with statistical significance, showing a least-squares mean LDL-C reduction of 33% (p<0.0001) compared to placebo at day 84. Mean and median reductions were 33% and 36%, respectively.
In an exploratory analysis of major adverse cardiac events, BROADWAY demonstrated a 21% reduction in the composite of coronary heart disease death, non-fatal myocardial infarction, non-fatal stroke and coronary revascularization favoring obicetrapib after one year. Results were published in The New England Journal of Medicine.
The TANDEM trial assessed the obicetrapib-ezetimibe fixed-dose combination in 407 patients with similar cardiovascular risk profiles. The combination therapy achieved a least-squares mean LDL-C reduction of 49% (p < 0.0001) compared to placebo at day 84, with mean and median reductions of 52% and 54%, respectively. These results were published in The Lancet.
BROOKLYN specifically evaluated obicetrapib in 354 patients with heterozygous familial hypercholesterolemia, achieving a least-squares mean LDL-C reduction of 36% (p < 0.0001) compared to placebo at day 84, with mean and median reductions of 36% and 39%, respectively.
Addressing Unmet Medical Need
Cardiovascular disease represents a significant global health burden, causing an estimated 17.9 million deaths annually according to Elcin Barker Ergun, Chief Executive Officer of the Menarini Group. "Despite the widespread availability of lipid lowering therapies, CVD-related deaths have risen, and patients remain above LDL-C targets, failing to achieve guidelines recommended LDL-C target goals," Ergun noted.
Obicetrapib is a novel, oral, low-dose cholesteryl ester transfer protein (CETP) inhibitor designed to overcome limitations of current LDL-lowering treatments. Across all Phase 2 and Phase 3 trials, the compound demonstrated statistically significant LDL-lowering combined with a side effect profile similar to placebo.
Strategic Partnership Structure
The Menarini License agreement, established in June 2022, provides NewAmsterdam with significant financial upside while transferring commercialization responsibilities to Menarini across 32 European countries including France, Germany, Italy, Spain, and the UK. Under the agreement, Menarini made an upfront payment of €115.0 million and committed €27.5 million in research and development funding.
NewAmsterdam is eligible to receive up to €863 million upon achievement of various clinical, regulatory and commercial milestones, with €30 million received to date. If approved and successfully commercialized, NewAmsterdam will receive tiered double-digit percentage royalties ranging from the low double-digits to mid-twenties as a percentage of net sales in the Menarini Territory.
Ongoing Development Program
NewAmsterdam continues to advance its global development program, including the Phase 3 PREVAIL cardiovascular outcomes trial, which commenced in March 2022. The company completed enrollment of PREVAIL in April 2024, randomizing over 9,500 patients to assess obicetrapib's potential to reduce major adverse cardiac events.
The company maintains a strong financial position with $835 million in cash as of year-end 2024, providing operational runway through 2026. This financial strength, combined with the milestone and royalty structure of the Menarini partnership, positions NewAmsterdam to advance its development programs without dilutive financing needs.
