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
Menarini Group announces positive topline data from the Phase 3 BROOKLYN clinical trial evaluating obicetrapib in patients with heterozygous familial hypercholesterolemia (HeFH). The trial met its primary endpoint, achieving a 36.3% reduction in LDL-C at week 12 and 41.5% reduction at week 52 compared to placebo (p<0.0001). Over 50% of patients achieved LDL-C levels below 70 mg/dl. Obicetrapib was well-tolerated with no increase in blood pressure and fewer treatment-related adverse events than placebo. The BROOKLYN trial is part of obicetrapib's global Phase 3 program, which includes four studies with over 12,250 patients. These results suggest obicetrapib could be a new, high-efficacy, oral option for difficult-to-treat HeFH patients.
Il Gruppo Menarini annuncia dati positivi di prima linea dalla sperimentazione clinica di Fase 3 BROOKLYN che valuta obicetrapib in pazienti con ipercolesterolemia familiare eterozigote (HeFH). Lo studio ha raggiunto il suo obiettivo primario, ottenendo una riduzione del 36,3% dell'LDL-C alla settimana 12 e una riduzione del 41,5% alla settimana 52 rispetto al placebo (p<0.0001). Oltre il 50% dei pazienti ha raggiunto livelli di LDL-C inferiori a 70 mg/dl. L'obicetrapib è stato ben tollerato senza aumento della pressione sanguigna e con meno eventi avversi legati al trattamento rispetto al placebo. Lo studio BROOKLYN è parte del programma globale di Fase 3 di obicetrapib, che comprende quattro studi con oltre 12.250 pazienti. Questi risultati suggeriscono che obicetrapib potrebbe rappresentare una nuova opzione orale ad alta efficacia per pazienti HeFH difficili da trattare.
El Grupo Menarini anuncia datos positivos preliminares del ensayo clínico en Fase 3 BROOKLYN que evalúa obicetrapib en pacientes con hipercolesterolemia familiar heterocigota (HeFH). El ensayo cumplió su objetivo principal, logrando una reducción del 36,3% en LDL-C a la semana 12 y una reducción del 41,5% a la semana 52 en comparación con el placebo (p<0.0001). Más del 50% de los pacientes alcanzaron niveles de LDL-C por debajo de 70 mg/dl. El obicetrapib fue bien tolerado sin aumento en la presión arterial y con menos eventos adversos relacionados con el tratamiento que el placebo. El ensayo BROOKLYN es parte del programa global de Fase 3 de obicetrapib, que incluye cuatro estudios con más de 12,250 pacientes. Estos resultados sugieren que obicetrapib podría ser una nueva opción oral de alta eficacia para pacientes de HeFH difíciles de tratar.
메나리니 그룹은 이형 가족성 고콜레스테롤혈증(HeFH) 환자에서 오비세트라피브를 평가한 3상 BROOKLYN 임상 시험에서 긍정적인 최종 결과를 발표했습니다. 이 시험은 주요 목표를 달성하여 12주차에 LDL-C 36.3% 감소를, 52주차에 41.5% 감소를 달성했습니다 (p<0.0001). 환자의 50% 이상이 LDL-C 수치를 70 mg/dl 이하로 낮추었습니다. 오비세트라피브는 잘 관 toler되었습니다 혈압 상승 없이 치료 관련 부작용이 플라시보보다 적었습니다. BROOKLYN 시험은 오비세트라피브의 글로벌 3상 프로그램의 일환으로, 12,250명 이상의 환자를 대상으로 한 네 가지 연구를 포함합니다. 이러한 결과는 오비세트라피브가 치료하기 어려운 HeFH 환자를 위한 새로운 고효능 경구 옵션이 될 수 있음을 시사합니다.
Le groupe Menarini annonce des données positives issues de l'essai clinique de phase 3 BROOKLYN évaluant obicetrapib chez des patients atteints d'hypercholestérolémie familiale hétérozygote (HeFH). L'essai a atteint son objectif principal, avec une réduction de 36,3 % du LDL-C à la semaine 12 et une réduction de 41,5 % à la semaine 52 par rapport au placebo (p<0.0001). Plus de 50 % des patients ont atteint des niveaux de LDL-C inférieurs à 70 mg/dl. L'obicetrapib a été bien toléré, sans augmentation de la pression artérielle et avec moins d'événements indésirables liés au traitement que le placebo. L'essai BROOKLYN fait partie du programme mondial de phase 3 d'obicetrapib, qui comprend quatre études avec plus de 12 250 patients. Ces résultats suggèrent qu'obicetrapib pourrait être une nouvelle option orale hautement efficace pour les patients HeFH difficiles à traiter.
Die Menarini-Gruppe gibt positive Hauptdaten aus der Phase-3-Studie BROOKLYN bekannt, die obicetrapib bei Patienten mit heterozygoter familiärer Hypercholesterinämie (HeFH) bewertet. Die Studie erreichte ihr primäres Ziel und erzielte eine Reduktion von 36,3% des LDL-C in der Woche 12 und eine Reduktion von 41,5% in der Woche 52 im Vergleich zur Placebo-Gruppe (p<0.0001). Über 50% der Patienten erreichten LDL-C-Werte unter 70 mg/dl. Obicetrapib wurde gut vertragen, ohne einen Anstieg des Blutdrucks und mit weniger behandlungsbedingten unerwünschten Ereignissen als das Placebo. Die BROOKLYN-Studie ist Teil des globalen Phase-3-Programms von Obicetrapib, das vier Studien mit über 12.250 Patienten umfasst. Diese Ergebnisse deuten darauf hin, dass Obicetrapib eine neue, hochwirksame orale Option für schwer zu behandelnde HeFH-Patienten sein könnte.
- Achieved primary endpoint with 36.3% LDL-C reduction at week 12 and 41.5% at week 52 (p<0.0001)
- Over 50% of patients achieved LDL-C levels below 70 mg/dl
- Well-tolerated with no increase in blood pressure
- Fewer treatment-related adverse events than placebo (4.3% vs 6.8%)
- Significant reductions in other biomarkers (non-HDL-C, ApoB, and Lp(a))
- Treatment discontinuation rate for obicetrapib was 7.6% (vs 14.4% for placebo)
Insights
The BROOKLYN trial results for obicetrapib in HeFH patients are highly promising. The 36.3% LDL-C reduction at week 12 and 41.5% reduction at week 52 are clinically significant, especially considering these patients were already on maximally tolerated lipid-lowering therapies. This suggests obicetrapib's potential as a powerful add-on therapy for difficult-to-treat HeFH patients.
Notably, over 50% of patients achieved an LDL-C level below 70 mg/dl, which aligns with current guidelines for high-risk patients. The consistent reductions in other biomarkers (non-HDL-C, ApoB and Lp(a)) further support obicetrapib's comprehensive lipid-lowering effect.
The safety profile is particularly encouraging. With no increase in blood pressure and a lower rate of study drug-related adverse events compared to placebo (4.3% vs 6.8%), obicetrapib appears well-tolerated. The lower discontinuation rate for obicetrapib (7.6%) versus placebo (14.4%) is also a positive sign for long-term adherence.
These results position obicetrapib as a potentially game-changing oral therapy for HeFH patients, addressing a significant unmet need in cardiovascular disease management.
The BROOKLYN trial results are indeed exciting for the field of cardiovascular medicine. HeFH patients, who make up 1 in 250 people worldwide, are notoriously difficult to treat due to their genetically elevated LDL-C levels. The fact that obicetrapib achieved such significant LDL-C reductions on top of maximally tolerated lipid-lowering therapies is remarkable.
What's particularly impressive is the durability of the effect, with LDL-C reduction actually improving from 36.3% at week 12 to 41.5% at week 52. This suggests that obicetrapib's efficacy may even increase over time, a highly desirable trait for a chronic therapy.
The safety profile is equally important. CETP inhibitors as a class have had a checkered history, with previous candidates failing due to off-target effects. Obicetrapib's clean safety profile, particularly the lack of blood pressure increase, is reassuring and distinguishes it from its predecessors.
If approved, obicetrapib could fill a critical gap in our therapeutic arsenal, offering a potent oral option for patients who can't reach their LDL-C goals with current therapies. This could potentially reduce the need for more invasive treatments like PCSK9 inhibitors or LDL apheresis in some patients.
The positive BROOKLYN trial results significantly boost obicetrapib's market potential. As the first of four pivotal studies, this success de-risks the overall development program and increases the likelihood of regulatory approval.
Obicetrapib's efficacy profile positions it as a potential best-in-class therapy for HeFH and possibly broader dyslipidemia indications. The once-daily oral dosing is a major advantage over injectable PCSK9 inhibitors, potentially leading to better patient adherence and market penetration.
The HeFH market, while relatively niche, represents a high-value opportunity due to the chronic nature of the disease and the high unmet need. Moreover, success in HeFH could pave the way for broader indications in hypercholesterolemia and ASCVD prevention.
For Menarini Group, securing European rights to obicetrapib looks increasingly strategic. The cardiovascular market in Europe is substantial and a novel, oral, high-efficacy LDL-C lowering agent could capture significant market share.
However, the competitive landscape should be considered. The ongoing CVOT (PREVAIL study) will be important for obicetrapib's commercial success, as positive outcomes data would be necessary to compete effectively with established therapies and potentially expand into broader patient populations.
Overall, these results strengthen obicetrapib's and Menarini's position in the evolving cardiovascular therapeutics market, with significant potential for future growth.
-- 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--
The BROOKLYN trial met its primary endpoint, achieving a LS mean reduction of
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
"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
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
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
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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