Menarini Announces Positive Topline Data from Pivotal Phase 3 BROOKLYN Clinical Trial Evaluating Efficacy, Safety and Tolerability of Obicetrapib in Patients with Heterozygous Familial Hypercholesterolemia

-- Achieved primary endpoint of LS mean reduction in LDL-C on top of maximally tolerated lipid modifying therapies at week 12 with statistically significant reduction (p<0.0001), which was sustained at week 52 (p<0.0001) --

-- Obicetrapib lowered LDL-C by 36.3% at week 12 and by 41.5% at week 52, compared to placebo --

-- Obicetrapib was well-tolerated; safety results comparable to placebo-- 

FLORENCE, Italy, July 29, 2024 /PRNewswire/ -- Menarini Group today announces positive topline data from the Phase 3 BROOKLYN clinical trial (NCT05425745) sponsored by NewAmsterdam Pharma Company N.V. ("NewAmsterdam"), a biopharmaceutical company which granted the Menarini Group an exclusive license to commercialize obicetrapib in Europe, either as a monotherapy or as part of a fixed dose combination with ezetimibe, for cardiovascular diseases. The phase 3 BROOKLYN clinical trial (NCT05425745), the first of four studies in NewAmsterdam's pivotal clinical development program, was designed to evaluate obicetrapib in adult patients with heterozygous familial hypercholesterolemia ("HeFH"), whose low-density lipoprotein cholesterol ("LDL-C") level is not adequately controlled, despite being on maximally tolerated lipid-lowering therapy.

The BROOKLYN trial met its primary endpoint, achieving a LS mean reduction of 36.3% (p < 0.0001) compared to placebo at week 12, which was sustained at 52 weeks with a LS mean LDL-C reduction of 41.5% (p < 0.0001). Over 50% of patients achieved an LDL-C level below 70 mg/dl. The reductions in other biomarkers, including non-HDL-C, ApoB, and Lp(a), met statistical significance and were consistent with prior studies.

In the study, obicetrapib proved to be well-tolerated, with no increase in blood pressure.  Any study drug related treatment emergent adverse events occurred in 6.8% patients in the placebo arm versus 4.3% patients in obicetrapib arm and no study drug related treatment emergent serious events were reported in both treatment arms. The treatment discontinuation rate for obicetrapib was 7.6% versus 14.4% for placebo.

"BROOKLYN data has confirmed obicetrapib's ability to significantly reduce LDL-C in HeFH patients, a population already on multiple lipid-lowering therapies. I am incredibly encouraged by these results, which suggest we may have a new, high-efficacy, oral option for a difficult-to-treat patient population" said Stephen Nicholls, M.B.B.S., Ph.D., Director, Monash Victorian Heart Institute and Professor of Cardiology, Monash University and principal investigator of the entire obicetrapib development program.

"Heterozygous Familial Hypercholesterolemia, or HeFH, affects 1 in 250 people worldwide and leads to increased risk of major adverse cardiovascular events, including stroke, myocardial infarction, or death, which often occur at a younger age than in the general population. While it's widely acknowledged that the increased risk is driven by elevated levels of LDL-C, many HeFH patients are unable to attain guideline-recommended LDL-C levels, despite currently available treatment options," said Katherine Wilemon Founder and CEO of the Family Heart Foundation. "HeFH patients are difficult to treat, often requiring multiple therapies to control their LDL-C levels. We are highly encouraged with these results and the potential to have another efficacious oral option."

"Cardiovascular diseases (CVDs) are the leading cause of death globally, taking an estimated 17.9 million lives each year. Despite the widespread availability of lipid lowering therapies, CVD-related deaths have risen and patients remain above LDL-C targets. Patients and their doctors need additional options. We are very pleased that BROOKLYN confirmed the ability of obicetrapib to significantly reduce LDL-C in a challenging patient population, over a duration of one year. This represents an important milestone in our commitment to offer the HeFH community in Europe a potential first in class, oral CETP-i in the fight against cardiovascular diseases, a mission of over 30 years for our company", said Elcin Barker Ergun, Chief Executive Officer of the Menarini Group. 

Design of the Pivotal Phase 3 BROOKLYN Clinical Trial

The 52-week, global, pivotal, Phase 3, randomized, double-blind, placebo-controlled multicenter study evaluated the efficacy and safety of 10 mg obicetrapib compared to placebo as an adjunct to maximally tolerated lipid-lowering therapies in patients with HeFH whose LDL-C is not adequately controlled. The study was conducted at sites in North America, Europe and Africa. A total of 354 patients were randomized 2:1 to receive 10 mg obicetrapib or placebo dosed as a once-daily oral treatment, with or without food. The mean baseline LDL-C for enrolled patients in the obicetrapib arm was 123 mg/dL despite high intensity statin use reported by approximately 79% of patients during screening. Females comprised approximately 53% of the study population and the median age of participants at baseline was 57 years.

The primary objective was to evaluate the effect of obicetrapib on LDL-C levels. Secondary objectives include evaluating the effect of obicetrapib on non-high-density lipoprotein cholesterol ("non-HDL-C"), apolipoprotein B ("ApoB"), and lipoprotein (a). The trial also evaluated the safety and tolerability profile of obicetrapib.

Obicetrapib's Global Pivotal Phase 3 Program

Obicetrapib global, pivotal Phase 3 clinical development program consists of four studies in over 12,250 patients, three for obicetrapib monotherapy and one for a fixed-dose combination ("FDC") with ezetimibe:

-  BROOKLYN evaluated obicetrapib in patients with HeFH, whose LDL-C is not adequately controlled, despite being on maximally tolerated lipid-lowering therapy (NCT05425745). Topline data reported in the third quarter of 2024.

-  BROADWAY is evaluating obicetrapib in adult patients with established ASCVD and/or HeFH, whose LDL-C is not adequately controlled, despite being on maximally tolerated lipid-lowering therapy (NCT05142722). Study enrollment of over 2,500 patients was completed in July 2023 and topline data are expected to be reported in the fourth quarter of 2024.

-  TANDEM is evaluating obicetrapib as part of a FDC tablet with ezetimibe, a non-statin oral LDL-lowering therapy, in patients with established ASCVD or multiple risk factors for ASCVD and/or HeFH, whose LDL-C is not adequately controlled despite being on maximally tolerated lipid-lowering therapy (NCT06005597).  Study enrollment of over 400 patients was completed in July 2024 and topline data are expected to be reported in the first quarter of 2025.

-  PREVAIL is a cardiovascular outcomes trial ("CVOT") evaluating obicetrapib in patients with a history of ASCVD, whose LDL-C is not adequately controlled, despite being on maximally tolerated lipid-lowering therapy (NCT05202509). Study enrollment of over 9,500 patients was completed in April 2024.

About Obicetrapib

Obicetrapib is a novel, under development, oral, low-dose CETP inhibitor to overcome the limitations of current LDL-lowering treatments. In each of the Phase 2 trials, ROSE, ROSE2, TULIP, and OCEAN, evaluating obicetrapib as monotherapy or in combination therapy, it was observed a statistically significant LDL-lowering combined with a good tolerability. Obicetrapib is being investigated in other three Phase 3 pivotal trials, BROADWAY and PREVAIL, evaluating obicetrapib as a monotherapy used as an adjunct to maximally tolerated lipid-lowering therapies to provide additional LDL-lowering and cardiovascular protection for cardiovascular disease ("CVD") patients and TANDEM, evaluating obicetrapib and ezetimibe as a fixed-dose combination. Patients enrollment in BROADWAY began in January 2022, and in TANDEM in March 2024; enrollment of BROADWAY was completed in July 2023, and TANDEM in July 2024. The Phase 3 PREVAIL cardiovascular outcomes trial, which is designed to assess the potential of obicetrapib to reduce occurrences of major adverse cardiovascular events, including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and non-elective coronary revascularization, commenced in March 2022 and the enrollment was completed in April 2024 with over 9,500 patients randomized.

About The Menarini Group

The Menarini Group is a leading international pharmaceutical and diagnostics company, with a turnover of $4.7 billion and over 17,000 employees. Menarini is focused on therapeutic areas of high unmet needs with products for cardiology, oncology, pneumology, gastroenterology, infectious diseases, diabetology, inflammation, and analgesia. With 18 production sites and 9 Research and Development centers, Menarini's products are available in 140 countries worldwide. For further information, please visit www.menarini.com.

About NewAmsterdam

NewAmsterdam Pharma (Nasdaq: NAMS) is a late-stage 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 studies, 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.

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