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
Menarini Group announced positive topline data from two Phase 3 trials evaluating Obicetrapib. The BROADWAY trial showed Obicetrapib achieved a 33% LDL-C reduction compared to placebo (p<0.0001), with 50% of patients reaching LDL-C levels below 55 mg/dL. A 21% reduction in major adverse cardiovascular events was observed at one year.
The TANDEM trial, testing a fixed-dose combination of Obicetrapib with Ezetimibe, demonstrated a 48.6% LDL-C reduction (p<0.0001), with over 70% of patients achieving target LDL-C levels. Both treatments were well-tolerated with safety profiles comparable to placebo. These trials are part of a larger Phase 3 program including over 12,250 patients across four studies.
Il Gruppo Menarini ha annunciato dati positivi preliminari provenienti da due studi di Fase 3 che valutano Obicetrapib. Lo studio BROADWAY ha mostrato che Obicetrapib ha raggiunto una riduzione del 33% del LDL-C rispetto al placebo (p<0.0001), con il 50% dei pazienti che ha raggiunto livelli di LDL-C inferiori a 55 mg/dL. È stata osservata una riduzione del 21% negli eventi cardiovascolari avversi maggiori a un anno.
Lo studio TANDEM, che ha messo alla prova una combinazione a dose fissa di Obicetrapib con Ezetimibe, ha dimostrato una riduzione del 48,6% del LDL-C (p<0.0001), con oltre il 70% dei pazienti che ha raggiunto i livelli target di LDL-C. Entrambi i trattamenti sono stati ben tollerati, con profili di sicurezza comparabili al placebo. Questi studi fanno parte di un programma di Fase 3 più ampio che include oltre 12.250 pazienti in quattro studi.
El Grupo Menarini anunció datos positivos de la línea principal de dos ensayos de Fase 3 que evalúan Obicetrapib. El ensayo BROADWAY mostró que Obicetrapib logró una reducción del 33% en el LDL-C en comparación con el placebo (p<0.0001), con el 50% de los pacientes alcanzando niveles de LDL-C por debajo de 55 mg/dL. Se observó una reducción del 21% en los eventos cardiovasculares adversos mayores a un año.
El ensayo TANDEM, que prueba una combinación a dosis fija de Obicetrapib con Ezetimibe, demostró una reducción del 48.6% en el LDL-C (p<0.0001), con más del 70% de los pacientes logrando los niveles de LDL-C objetivo. Ambos tratamientos fueron bien tolerados, con perfiles de seguridad comparables al placebo. Estos ensayos son parte de un programa más amplio de Fase 3 que incluye a más de 12,250 pacientes en cuatro estudios.
메나리니 그룹은 오비세트라픽을 평가하는 두 개의 3상 시험에서 긍정적인 주요 데이터를 발표했습니다. 브로드웨이 시험에서는 오비세트라픽이 위약에 비해 33% LDL-C 감소를 달성했으며(p<0.0001), 환자의 50%가 LDL-C 수치를 55 mg/dL 이하로 유지했습니다. 1년 후 주요 심혈관 이상 사건이 21% 감소한 것으로 나타났습니다.
탄뎀 시험은 오비세트라픽과 에제티미브의 고정 용량 조합을 시험하며 48.6% LDL-C 감소를 보여주었고(p<0.0001), 환자의 70% 이상이 목표 LDL-C 수치를 달성했습니다. 두 치료법 모두 잘 견뎌냈으며 위약과 비교했을 때 안전성 프로필이 유사했습니다. 이러한 시험들은 12,250명 이상의 환자를 포함하는 더 큰 3상 프로그램의 일환입니다.
Le Groupe Menarini a annoncé des données positives préliminaires provenant de deux essais de Phase 3 évaluant Obicetrapib. L'essai BROADWAY a montré qu'Obicetrapib a obtenu une réduction de 33 % du LDL-C par rapport au placebo (p<0.0001), avec 50 % des patients atteignant des niveaux de LDL-C inférieurs à 55 mg/dL. Une réduction de 21 % des événements cardiovasculaires majeurs a été observée après un an.
L'essai TANDEM, testant une combinaison à dose fixe d'Obicetrapib avec l'ézétimibe, a démontré une réduction du LDL-C de 48,6 % (p<0.0001), avec plus de 70 % des patients atteignant les niveaux cibles de LDL-C. Les deux traitements ont été bien tolérés, avec des profils de sécurité comparables à ceux du placebo. Ces essais font partie d'un programme de Phase 3 plus large incluant plus de 12 250 patients dans quatre études.
Die Menarini-Gruppe hat positive Zwischenergebnisse aus zwei Phase-3-Studien zur Bewertung von Obicetrapib bekannt gegeben. Die BROADWAY-Studie zeigte, dass Obicetrapib eine Reduktion des LDL-C um 33% im Vergleich zu Placebo erreichte (p<0.0001), wobei 50% der Patienten LDL-C-Werte unter 55 mg/dL erreichten. Nach einem Jahr wurde eine Reduktion der schwerwiegenden unerwünschten kardiovaskulären Ereignisse um 21% beobachtet.
Die TANDEM-Studie, die eine Fixkombination von Obicetrapib mit Ezetimib testete, zeigte eine Reduktion des LDL-C um 48,6% (p<0.0001), wobei über 70% der Patienten die Zielwerte für LDL-C erreichten. Beide Behandlungen wurden gut vertragen, mit Sicherheitsprofilen, die mit denen von Placebo vergleichbar sind. Diese Studien sind Teil eines größeren Phase-3-Programms, das über 12.250 Patienten in vier Studien umfasst.
- 33% LDL-C reduction achieved in BROADWAY trial (p<0.0001)
- 48.6% LDL-C reduction in TANDEM trial with combination therapy (p<0.0001)
- 21% reduction in major adverse cardiovascular events in BROADWAY
- Strong safety profile comparable to placebo in both trials
- 50-70% of patients reached target LDL-C levels below 55 mg/dL
- None.
Insights
The Phase 3 BROADWAY and TANDEM trials demonstrate compelling efficacy for Obicetrapib, showcasing 33% LDL-C reduction as monotherapy and 48.6% reduction when combined with Ezetimibe. The 21% reduction in major adverse cardiovascular events (MACE) in BROADWAY, though not a primary endpoint, suggests promising cardiovascular outcomes.
The drug's safety profile is particularly noteworthy, with discontinuation rates comparable to or better than placebo (11.1% vs 12.4%). Importantly, glycemic control and renal function actually favored Obicetrapib, addressing key safety concerns for cardiovascular medications. The achievement of LDL-C targets below 55 mg/dL in 50% of BROADWAY and 70% of TANDEM patients represents a significant clinical breakthrough.
These robust clinical results significantly strengthen NewAmsterdam's market position in the cardiovascular space. With a
The fixed-dose combination with Ezetimibe adds another valuable commercial opportunity, potentially capturing both monotherapy and combination therapy markets. The strong safety profile and once-daily oral administration could drive significant market adoption, especially compared to injectable alternatives.
– 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
– In BROADWAY a
-- In both studies, Obicetrapib monotherapy and the fixed dose combination with Ezetimibe were shown to be 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
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
Major adverse cardiovascular events table: | ||||
Placebo (n = 844) | Obicetrapib 10 mg (n= 1686) | Hazard Ratio | ||
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
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
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
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
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
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
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
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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