Menarini Group announces Positive Topline Data from Pivotal Phase 3 BROADWAY & TANDEM Clinical Trials Evaluating Obicetrapib and the Fixed-Dose Combination Obicetrapib with Ezetimibe 10 mg

– Both pivotal studies achieved primary endpoints of LS mean reduction in LDL-C on top of maximally tolerated lipid-modifying therapies with high statistical significance (p<0.0001)

– Approximately 50% of patients in BROADWAY (Obicetrapib monotherapy) and over 70% of patients in TANDEM (Fixed Dose Combination Obicetrapib with Ezetimibe) achieved LDL-C target below 55 mg/dL

– In BROADWAY a 21% reduction in major adverse cardiovascular events favoring Obicetrapib was observed at one year

-- In both studies, Obicetrapib monotherapy and the fixed dose combination with Ezetimibe were shown to be well tolerated 

FLORENCE, Italy, Dec. 16, 2024 /CNW/ -- Menarini Group today announces positive topline data from the Phase 3 BROADWAY (NCT05142722) and the Phase 3 TANDEM (NCT06005597) clinical trials sponsored by NewAmsterdam Pharma Company N.V. (Nasdaq: NAMS or "NewAmsterdam" 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.

The Phase 3 BROADWAY clinical trial (NCT05142722) was designed to evaluate 10 mg Obicetrapib in adult patients with heterozygous familial hypercholesterolemia ("HeFH") and/or established atherosclerotic cardiovascular disease ("ASCVD"), whose LDL-C is not adequately controlled, despite being on maximally tolerated lipid-lowering therapy.

The phase 3 TANDEM clinical trial (NCT06005597) was designed to evaluate 10 mg Obicetrapib and 10 mg Ezetimibe fixed-dose combination in adult patients with HeFH and/or ASCVD or multiple ASCVD risk factors, whose LDL-C is not adequately controlled, despite being on maximally tolerated lipid-lowering therapy. 

The primary endpoint in BROADWAY was the least-squares mean of the percent change in LDL-C from baseline to day 84 for Obicetrapib 10 mg compared to placebo. The primary endpoint was achieved with statistical significance with an LDL-C reduction of 33% (p<0.0001).

LDL-C percentage change at Day 84:
	Placebo (n=844)	Obicetrapib 10 mg (n=1686)	Difference
Mean	-2 %	-35 %	-33 %
Median	-4 %	-40 %	-36 %
LS mean	+3 %	-30 %	-33 %

The observed changes in other biomarkers, including increase of high-density lipoprotein cholesterol ("HDL-C") and reduction of non-HDL-C, lipoprotein(a) ("Lp(a)"), apolipoprotein B ("ApoB"), and Apolipoprotein A1 (ApoA1) were positive and consistent with data reported from prior clinical trials.

As part of the safety analysis, key adverse events ("AE") of special interests were monitored. Among these AEs, glycemic control and renal function favoured Obicetrapib.

In addition, the BROADWAY trial adjudicated MACE, including death, non-fatal myocardial infarction, non-fatal stroke and coronary revascularization showing a 21% reduction in the first 4-point MACE favoring Obicetrapib.

Major adverse cardiovascular events table:
	Placebo (n = 844)	Obicetrapib 10 mg (n= 1686)	Hazard Ratio	95% CI
All-cause mortality – no. (%)	12 (1.4)	19 (1.1)	0.83	(0.40-1.71)
Coronary heart death – no. (%)	5 (0.6)	8 (0.5)	0.80	(0.26-2.44)
First 4-point MACE – no. (%)	44 (5.2)	70 (4.2)	0.79	(0.54-1.15)
4-point MACE: CHD death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularization. MACE was not a primary or secondary endpoint of the BROADWAY trial.

Overall, Obicetrapib was also observed to be well tolerated, with safety data, including blood pressure, comparable to placebo. The treatment discontinuation rate for the Obicetrapib arm was 11.1% versus 12.4% for placebo. The incidence of treatment-emergent adverse events ("TEAEs"), study-drug related TEAEs, and treatment-emergent serious adverse events ("TESAEs") are summarized in the table below.

	Placebo (n=843)	Obicetrapib 10 mg (n=1,685)
Any TEAEs – no. (%)	513 (60.9)	1007 (59.8)
Any trial drug related TEAEs – no (%)	39 (4.6)	76 (4.5)
Any TEAEs leading to discontinuation of trial drug – no. (%	43 (5.1)	68 (4.0)
Any TESAEs – no. (%)	117 (13.9)	211 (12.5)

The co-primary endpoints in TANDEM were percent change from baseline in LDL-C of the fixed-dose combination compared to each monotherapy arm after 84 days and Obicetrapib 10 mg compared to placebo after day 84. Secondary endpoints incorporated percent changes from baseline in other biomarkers, including Lp(a), non-HDL-c and APO B.

The TANDEM trial met all co-primary endpoints, including the fixed dose combination Obicetrapib with Ezetimibe achieving an LS mean reduction of 48.6% (p < 0.0001) compared to placebo at day 84.

LDL-C percentage change at Day 84

	Ezetimibe (n=101)	Obicetrapib (n=102)	Obicetrapib and Ezetimibe FDC (n=102)
Day 84 – from placebo
Mean %	-23.3	-35.5	-52.2
Median %	-22.6	-37.2	-54.0
LS mean %	-20.7	-31.9	-48.6
Comparison to pbo	-	(p<0.0001)	(p<0.0001)
Comparison to eze 10 mg	-	-	(p<0.0001)
Comparison to obi 10 mg	-	-	(p=0.0007)

In the trial, the fixed-dose combination of Obicetrapib and Ezetimibe was observed to be well tolerated, with safety data comparable to placebo. The below table summarizes study drug-related treatment emergent adverse events ("TEAEs") and study drug-related treatment emergent serious adverse events ("TESAEs").

	Placebo (n=102)	Ezetimibe (n=101)	Obicetrapib (n=102)	Obicetrapib / Ezetimibe FDC (n=102)
Any study drug-related TEAEs	4 (3.9 %)	3 (3.0 %)	7 (6.9 %)	3 (2.9 %)
Any study drug-related TEAEs leading to discontinuation of study drug	2 (2.0 %)	1 (1.0 %)	6 (5.9 %)	1 (1.0 %)
Any study drug related TESAEs	0 (0.0 %)	0 (0.0 %)	0 (0.0 %)	0 (0.0 %)

"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, many patients failing to achieve guidelines recommended LDL.C target goals. Patients and their doctors need additional options. We are very pleased that BROADWAY and TANDEM data and previously announced BROOKLYN data confirmed the ability of Obicetrapib as a monotherapy or in a fixed dose combination with ezetimibe to significantly reduce LDL-C and help patients achieve recommended target goals. This represents a key milestone in our commitment to offer patients suffering from cardiovascular diseases in Europe, a potential first in class, low dose, once daily oral treatment 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 BROADWAY 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 ASCVD and/or HeFH whose LDL-C is not adequately controlled. The study was conducted at sites in North America, Europe, Asia and Australia. A total of 2,530 patients were randomized 2:1 to receive 10 mg Obicetrapib or placebo dosed as a once-daily oral treatment, with or without food for 52 weeks. The mean baseline LDL-C for enrolled patients in the Obicetrapib arm was approximately 100 mg/dL despite high intensity statin use reported by nearly 70% of patients during screening. Females comprised approximately 34% of the study population and the median age of participants at baseline was 65 years.

The primary endpoint was percent change from baseline in LDL-C of Obicetrapib 10 mg compared to placebo after 84 days which showed a reduction of 33% with imputation. Secondary endpoints also included percent changes from baseline of Obicetrapib 10 mg compared to placebo in ApoB, Lp(a), ApoA1, HDL-C, non-HDL-C, total cholesterol, and triglycerides at day 84, and on LDL-C levels at days 180 and 365 (-34% and -24%, respectively with p<0.0001). Other outcome measures include time from randomization until the first confirmed occurrence of MACE in the Obicetrapib arm compared to placebo. The trial also evaluated the safety and tolerability profile of Obicetrapib.

Design of the Pivotal Phase 3 TANDEM Clinical Trial

The pivotal, Phase 3, randomized, double-blind, four-arm, placebo-controlled multicenter study evaluated the effect of 10 mg Obicetrapib and 10 mg ezetimibe as a fixed-dose combination on LDL-C levels, compared to both ezetimibe 10 mg and Obicetrapib 10 mg monotherapy and to placebo. The study was conducted at sites across the United States, and a total of 407 patients with HeFH and/or ASCVD or ASCVD risk equivalents, who had a baseline LDL-C of at least 70 mg/dL, were randomized 1:1:1:1 to receive 10 mg Obicetrapib and 10 mg ezetimibe fixed-dose combination, 10 mg Obicetrapib, 10 mg ezetimibe or placebo for an 84-day treatment period. The mean baseline LDL-C for enrolled patients in the obicetrapib-ezetimibe arm was 97 mg/dL despite high intensity statin use reported by approximately 74% of patients during screening. In addition to measuring the co-primary endpoints and secondary endpoints, 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 the 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). Study enrollment of over 350 patients was completed in April 2023. Topline data reported in the third quarter of 2024.
• BROADWAY evaluated 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. Topline data reported in the fourth quarter of 2024.
• TANDEM evaluated 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. Topline data reported in November 2024
• 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, oral, low-dose CETP inhibitor under development to overcome the limitations of current LDL-lowering treatments. In each of the Phase 2 trials, ROSE2, TULIP, ROSE, as well as the Phase 3 BROOKLYN, BROADWAY and TANDEM trials, evaluating Obicetrapib as monotherapy or combination therapy, it was observed statistically significant LDL-lowering combined with a side effect profile similar to that of placebo. 
The Phase 3 study cardiovascular outcomes trial PREVAIL commenced in March 2022 and 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. The enrollment of PREVAIL was completed in April 2024 and randomized over 9,500 patients.

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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SOURCE Menarini Industrie Farmaceutiche Riunite

Menarini, Valeria Speroni Cardi, [email protected], + 39 05556801; Spectrum Science on behalf of NewAmsterdam, Bryan Blatstein, [email protected], P: 1-917-714-2609