NewAmsterdam Pharma Announces Late-Breaking Data from BROADWAY and TANDEM Pivotal Studies Published in Leading Medical Journals and Presented at the European Atherosclerosis Society (EAS) Congress 2025

Rhea-AI Summary

NewAmsterdam Pharma (NAMS) announced groundbreaking results from their BROADWAY and TANDEM Phase 3 studies of obicetrapib, published in The New England Journal of Medicine and The Lancet. The studies demonstrated that obicetrapib, when used with statins, reduced LDL-C by 50% in combination with ezetimibe and 35% as monotherapy. Key findings include a 21% reduction in major adverse cardiovascular events and a 45% reduction in Lp(a) levels across multiple trials. The TANDEM trial showed that over 60% of patients achieved LDL-C reductions greater than 50%, with 70% reaching levels below 55 mg/dL. Phase 2 data revealed that obicetrapib combined with moderate-dose statins reduced LDL-C by approximately 70%. The drug demonstrated a favorable safety profile comparable to placebo across all trials.

Positive

• Significant 50% LDL-C reduction when combined with ezetimibe and 35% as monotherapy
• 21% reduction in major adverse cardiovascular events (MACE)
• 45% reduction in Lp(a) levels across multiple trials
• 70% of patients achieved LDL-C levels below 55 mg/dL in TANDEM trial
• Phase 2 data showed up to 69% LDL-C reduction with moderate-intensity statins
• Favorable safety profile comparable to placebo
• Demonstrated synergistic effects with existing treatments

Negative

• Confidence interval for MACE reduction (0.54-1.15) includes 1.0, indicating the result is not statistically significant

Insights

Cardiovascular Medicine Specialist

NewAmsterdam's obicetrapib shows impressive LDL-C reductions with positive cardiovascular outcomes signal, positioning it as a potentially transformative oral therapy.

The publication of NewAmsterdam's Phase 3 BROADWAY and TANDEM trials in The New England Journal of Medicine and The Lancet represents a significant milestone. These results demonstrate that obicetrapib effectively reduces LDL-C by 35% as monotherapy and 50% when combined with ezetimibe, on top of statins. Most notably, when combined with moderate-intensity statins in Phase 2 studies, LDL-C reductions reached approximately 70% – approaching the efficacy of injectable PCSK9 inhibitors but in a convenient oral formulation.

The 21% observed reduction in major adverse cardiovascular events (MACE) in BROADWAY (HR=0.79) is particularly meaningful, as it suggests actual clinical benefit beyond just biomarker improvement. While the confidence interval (0.54-1.15) crosses 1.0, this signal is encouraging for a study not primarily powered for outcomes.

The 45% reduction in lipoprotein(a) across pooled Phase 3 data is another significant finding, as elevated Lp(a) is an independent risk factor for cardiovascular disease affecting approximately 50% of ASCVD patients. This dual effect on both LDL-C and Lp(a) addresses important components of residual cardiovascular risk.

The safety profile appears remarkably clean, with tolerability comparable to placebo – critical for a medication intended for chronic use. This contrasts favorably with other cholesterol-lowering agents that often have muscle-related side effects.

The fixed-dose combination with ezetimibe, achieving LDL-C levels below 55 mg/dL in 70% of patients, could position obicetrapib as an attractive non-statin option for the large population of patients who struggle to achieve target lipid levels with existing therapies.

Biotechnology Investment Analyst

The publication of NewAmsterdam's pivotal trial data in top-tier journals significantly enhances the credibility and commercial potential of obicetrapib. Simultaneous publications in The New England Journal of Medicine and The Lancet represent exceptional validation from the scientific community, dramatically increasing visibility among prescribing physicians.

The efficacy profile positions obicetrapib as potentially best-in-class among oral LDL-C lowering therapies. The 35% reduction as monotherapy and 50% reduction when combined with ezetimibe address a significant market gap between statins and injectable PCSK9 inhibitors. The convenience of an oral therapy combined with this efficacy level creates a compelling value proposition.

The 21% MACE reduction signal, though exploratory, is particularly relevant for payers and formulary decisions. While not statistically significant (CI 0.54-1.15), this outcome signal strengthens reimbursement potential – critical for commercial success in the cardiovascular market.

From a commercial perspective, the fixed-dose combination with ezetimibe is strategically intelligent, simplifying treatment and potentially extending patent protection. The 45% Lp(a) reduction creates additional differentiation in a crowded lipid management market.

Importantly, NewAmsterdam has now assembled a comprehensive data package for regulatory submissions, with results consistent across multiple trials and patient populations. The favorable safety profile, comparable to placebo, removes a critical hurdle that has plagued previous CETP inhibitors and will likely facilitate adoption among risk-averse clinicians treating a generally stable patient population.

– Late Breaking BROADWAY and TANDEM data presented at EAS 2025 and simultaneously published in The New England Journal of Medicine (BROADWAY) and The Lancet (TANDEM) –

– Phase 3 data showed that obicetrapib as an adjunct to statins, whether in combination with ezetimibe or as monotherapy, reduced LDL-C by 50% and 35%, respectively; in addition, Phase 2 data of obicetrapib in combination with moderate-dose statins showed LDL-C reductions of approximately 70% –

– 21% observed reduction in major adverse cardiovascular events (HR=0.79, CI 0.54-1.15) in BROADWAY trial –

– Pooled Phase 3 data showed Lp(a) reductions of 45% across BROADWAY, TANDEM, and BROOKLYN trials for patients with increased risk levels of Lp(a) from 50-150 nmol/L at baseline –

NAARDEN, The Netherlands and MIAMI, May 07, 2025 (GLOBE NEWSWIRE) -- NewAmsterdam Pharma Company N.V. (Nasdaq: NAMS or “NewAmsterdam,” “we,” or the “Company”), a late-stage, clinical biopharmaceutical company developing oral, non-statin medicines for patients at risk of cardiovascular disease (“CVD”) with elevated low-density lipoprotein cholesterol (“LDL-C”), for whom existing therapies are not sufficiently effective or well-tolerated, today announced additional data from the BROADWAY and TANDEM pivotal Phase 3 studies were presented as late-breaking oral presentations at the European Atherosclerosis Society Congress (“EAS”) 2025 and simultaneously published in The New England Journal of Medicine (BROADWAY) and The Lancet (TANDEM).

“We are proud to share what we believe to be compelling clinical data from two comprehensive clinical trials conducted in the CVD space, now published in leading peer-reviewed journals and as late-breaking presentations at EAS 2025,” said Michael Davidson, M.D., Chief Executive Officer of NewAmsterdam Pharma. “We believe the additional data presented today further supports obicetrapib as a meaningful advancement in the development of an oral medication to be used adjunctively to statins. These results will support global regulatory filings and reinforce our belief that obicetrapib has the potential to be an effective, once-daily, oral treatment that significantly reduces LDL-C.”

Key previously-reported findings from the BROADWAY clinical trial evaluating obicetrapib in patients with atherosclerotic cardiovascular disease (“ASCVD”) and/or heterozygous familial hypercholesterolemia (“HeFH”):

• Achieved primary endpoint showing a 33% (p<0.0001) reduction compared to placebo in LDL-C on top of maximally tolerated lipid modifying therapies at day 84.
• In an exploratory safety analysis we observed a 21% relative reduction in the exploratory endpoint of major adverse cardiovascular events (“MACE”) (HR=0.79, CI 0.54-1.15), including coronary heart disease death, non-fatal myocardial infarction, non-fatal stroke, and coronary revascularization.
• Observed improvements across key biomarkers, including high-density lipoprotein cholesterol (“HDL-C”), non-HDL-C, lipoprotein(a) (“Lp(a)”), apolipoprotein B (“ApoB”), and Apolipoprotein A1 (“ApoA1”), were consistent with prior clinical trials.
• Obicetrapib was observed to be well-tolerated, with a safety profile that was comparable to placebo, consistent with all clinical trials conducted to date.

“Despite broad availability of lipid-lowering medications, many patients are unable to reach their LDL-C goals, and CVD-related mortality rates continue to rise,” said Stephen Nicholls, M.B.B.S., Ph.D., Director of the Monash Victorian Heart Institute and Professor of Cardiology at Monash University. “The additional data presented today further supports the potential of obicetrapib.”

Key previously-reported findings from the TANDEM clinical trial evaluating the fixed-dose combination (“FDC”) of obicetrapib 10 mg and ezetimibe 10 mg in patients with ASCVD or ASCVD risk factors and/or HeFH:

• Obicetrapib and ezetimibe FDC achieved all co-primary endpoints of reduction in LDL-C on top of maximally tolerated lipid-modifying therapies compared to each of placebo, ezetimibe 10 mg, and obicetrapib 10 mg monotherapy at day 84 with statistically significant LDL-C reduction of 48.6% (p<0.001) observed with the FDC versus placebo.
• Obicetrapib and ezetimibe FDC observed to lower LDL-C by greater than 50% in over 60% of patients at day 84, with more than 70% of patients achieving LDL-C levels below 55 mg/dL.
• Obicetrapib and ezetimibe FDC was observed to be well tolerated, with safety results comparable to placebo.
  

“The TANDEM data presented today are highly encouraging and this new drug in combination with ezetimibe delivered a roughly 50% LDL-C reduction and improvements across other lipid parameters,” said Ashish Sarraju, M.D., the study's lead author and preventive cardiologist at Cleveland Clinic. “Simple and effective oral therapies like this are needed alongside maximally tolerated statins in the current CVD treatment paradigm.”

In addition, today the Company announced the pooled Lp(a) data across BROADWAY, BROOKLYN, and TANDEM. As part of the analysis, the Company assessed changes in Lp(a) in patients with baseline levels ranging from 50-150 nmol/L. In this pooled population, obicetrapib was observed to produce a median placebo-adjusted reduction of 45% in Lp(a) after 12 weeks.

“This data is meaningful as approximately 50% of patients with ASCVD have Lp(a) greater than 50 nmol/L that is likely to promote residual risk. Importantly, 60-75% of those with Lp(a) levels above 50 nmol/L are below 150 nmol/L,” said John Kastelein, M.D., Ph.D., FESC, Chief Scientific Officer of NewAmsterdam. “Understanding residual risk is important for the overall treatment of ASCVD. Obicetrapib has shown clinically relevant reductions across multiple biomarkers of risk, including Lp(a) and LDL particles, and we believe obicetrapib could help change the definition of what an effective cardiometabolic therapy provides for patients.”

Additional data presented at EAS 2025 further highlights obicetrapib’s potential as a foundational therapy in CVD management, and included the following:

• Obicetrapib, in a phase 2 trial, combined with moderate intensity statins, atorvastatin 20 mg or rosuvastatin 10 mg, observed to lower LDL-C by 69% and 64%, respectively, compared to placebo.
• Obicetrapib, in a phase 2 trial, observed to significantly increase antioxidant levels in HDL and generally decrease levels of oxidized LDL particles antioxidant levels in non-HDL, in humans, supporting the well-established evidence that HDL protects against LDL oxidation.
• Observed synergy in obicetrapib plus ezetimibe in the prevention of plaque formation in a relevant pre-clinical model with a more than a 20% greater effect observed from the combination of obicetrapib and ezetimibe than if obicetrapib and ezetimibe were used independently (-98% vs -78%, respectively).
• Mendelian randomization study and meta-analysis showed that the HDL increase conferred by CETP-inhibition did not have any negative safety effects, with hazard ratio point estimates below 1 for all-cause and CVD mortality.

About Obicetrapib

Obicetrapib is a novel, oral, low-dose CETP inhibitor that NewAmsterdam is developing to overcome the limitations of current LDL-lowering treatments. In each of the Company’s Phase 2 trials, ROSE2, TULIP, ROSE, and OCEAN, as well as the Company’s Phase 3 BROOKLYN, BROADWAY and TANDEM trials, evaluating obicetrapib as monotherapy or combination therapy, the Company observed statistically significant LDL-lowering combined with a side effect profile similar to that of placebo. The Company commenced the Phase 3 PREVAIL cardiovascular outcomes trial in March 2022, which is designed to assess the potential of obicetrapib to reduce occurrences of MACE. The Company completed enrollment of PREVAIL in April 2024 and randomized over 9,500 patients. Commercialization rights of obicetrapib in Europe, either as a monotherapy or as part of a fixed-dose combination with ezetimibe, have been exclusively granted to the Menarini Group, an Italy-based, leading international pharmaceutical and diagnostics company.

About Cardiovascular Disease

Cardiovascular disease remains the leading cause of death globally, despite the availability of lipid-lowering therapies (LLTs). By 2050 more than 184 million U.S. adults are expected to be affected by CVD and hypertension, including 27 million with coronary heart disease and 19 million with stroke. In the United States from 2019 through 2022, CVD age-adjusted mortality rates increased by 9%, reversing the trend observed since 2010 and undoing nearly a decade of progress. Despite the availability of high-intensity statins and non-statin LLTs, LDL-C target level attainment remains low, contributing to residual cardiovascular risk, and underscoring a significant clinical need for improved therapeutic regimens. Even with 269 million LLT prescriptions written over the last 12 months, 30 million under-treated US adults are not at their risk-based LDL-C goal, of which 13 million have ASCVD. Less than 1 in 4 patients with ASCVD achieve an LDL-C goal of less than 70 mg/dL and only 10% of very high risk ASCVD patients achieve the goal below 55 mg/dL. In addition to the 30 million under-treated U.S. adults, there are 10 million patients diagnosed with elevated LDL-C who are not taking any LLTs including statins. Beyond LDL-C, additional factors are at play, such as lifestyle choices, tobacco use, and obesity, as well as inflammation, thrombosis, triglyceride levels, elevated Lp(a) levels, and type 2 diabetes.

About NewAmsterdam

NewAmsterdam Pharma (Nasdaq: NAMS) is a late-stage, clinical biopharmaceutical company whose mission is to improve patient care in populations with metabolic diseases where currently approved therapies have not been adequate or well tolerated. We seek to fill a significant unmet need for a safe, well-tolerated and convenient LDL-lowering therapy. In multiple Phase 3 trials, NewAmsterdam is investigating obicetrapib, an oral, low-dose and once-daily CETP inhibitor, alone or as a fixed-dose combination with ezetimibe, as LDL-C lowering therapies to be used as an adjunct to statin therapy for patients at risk of CVD with elevated LDL-C, for whom existing therapies are not sufficiently effective or well tolerated.

Forward-Looking Statements

Certain statements included in this document that are not historical facts are forward-looking statements for purposes of the safe harbor provisions under the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements generally are accompanied by words such as “believe,” “may,” “will,” “estimate,” “continue,” “anticipate,” “intend,” “expect,” “should,” “would,” “plan,” “predict,” “potential,” “seem,” “seek,” “future,” “outlook” and similar expressions that predict or indicate future events or trends or that are not statements of historical matters. These forward-looking statements include, but are not limited to, statements regarding the Company’s business and strategic plans, the Company’s commercial opportunity, the therapeutic and curative potential of the Company’s product candidate, the Company’s clinical trials and the timing for enrolling patients, the timing and forums for announcing data, the achievement and timing of regulatory approvals, and plans for commercialization. These statements are based on various assumptions, whether or not identified in this document, and on the current expectations of the Company’s management and are not predictions of actual performance. These forward-looking statements are provided for illustrative purposes only and are not intended to serve as and must not be relied on as a guarantee, an assurance, a prediction, or a definitive statement of fact or probability. Actual events and circumstances are difficult or impossible to predict and may differ from assumptions. Many actual events and circumstances are beyond the control of the Company. These forward-looking statements are subject to a number of risks and uncertainties, including changes in domestic and foreign business, market, financial, political, and legal conditions; risks related to the approval of the Company’s product candidate and the timing of expected regulatory and business milestones, including potential commercialization; whether topline, initial or preliminary results from a particular clinical trial will be predictive of the final results of that trial and whether results of early clinical trials will be indicative of the results of later clinical trials, or whether projections regarding clinical outcomes will reflect actual results in future clinical trials or clinical use of our product candidate, if approved; ability to negotiate definitive contractual arrangements with potential customers; the impact of competitive product candidates; ability to obtain sufficient supply of materials; global economic and political conditions, including the Russia-Ukraine and Israel-Hamas conflicts; the effects of competition on the Company’s future business; and those factors described in the Company’s public filings with the Securities and Exchange Commission. Additional risks related to the Company’s business include, but are not limited to: uncertainty regarding outcomes of the Company’s ongoing clinical trials, particularly as they relate to regulatory review and potential approval for its product candidate; risks associated with the Company’s efforts to commercialize a product candidate; the Company’s ability to negotiate and enter into definitive agreements on favorable terms, if at all; the impact of competing product candidates on the Company’s business; intellectual property related claims; the Company’s ability to attract and retain qualified personnel; and ability to continue to source the raw materials for the Company’s product candidate. If any of these risks materialize or the Company’s assumptions prove incorrect, actual results could differ materially from the results implied by these forward-looking statements. There may be additional risks that the Company does not presently know or that the Company currently believes are immaterial that could also cause actual results to differ from those contained in the forward-looking statements. In addition, forward-looking statements reflect the Company’s expectations, plans, or forecasts of future events and views as of the date of this document and are qualified in their entirety by reference to the cautionary statements herein. The Company anticipates that subsequent events and developments may cause the Company’s assessments to change. These forward-looking statements should not be relied upon as representing the Company’s assessment as of any date subsequent to the date of this communication. Accordingly, undue reliance should not be placed upon the forward-looking statements. Neither the Company nor any of its affiliates undertakes any obligation to update these forward-looking statements, except as may be required by law.

Company Contact
Matthew Philippe
P: 1-917-882-7512
matthew.philippe@newamsterdampharma.com

Media Contact
Spectrum Science on behalf of NewAmsterdam
Jaryd Leady
P: 1-856-803-7855
jleady@spectrumscience.com

Investor Contact
Precision AQ on behalf of NewAmsterdam
Austin Murtagh
P: 1-212-698-8696
austin.murtagh@precisionaq.com

FAQ

What were the main results of NAMS's BROADWAY and TANDEM trials for obicetrapib?

The trials showed obicetrapib reduced LDL-C by 50% when combined with ezetimibe and 35% as monotherapy. It also demonstrated a 21% reduction in major adverse cardiovascular events and 45% reduction in Lp(a) levels.

How effective is NAMS's obicetrapib when combined with moderate-dose statins?

Phase 2 trial data showed obicetrapib combined with moderate-dose statins reduced LDL-C by 69% with atorvastatin 20mg and 64% with rosuvastatin 10mg compared to placebo.

What percentage of patients achieved target LDL-C levels in NAMS's TANDEM study?

Over 60% of patients achieved LDL-C reductions greater than 50%, and more than 70% of patients reached LDL-C levels below 55 mg/dL.

What was the safety profile of NAMS's obicetrapib in clinical trials?

Obicetrapib was well-tolerated with a safety profile comparable to placebo across all clinical trials conducted to date.

How did NAMS's obicetrapib affect Lp(a) levels in patients?

In patients with baseline Lp(a) levels of 50-150 nmol/L, obicetrapib produced a median placebo-adjusted reduction of 45% after 12 weeks.