NewAmsterdam Announces Positive Results from ROSE2, Phase 2 Trial Evaluating Obicetrapib in Combination with Ezetimibe as an Adjunct to High-Intensity Statin Therapy
- Category: Small Molecules
- Published on Tuesday, 17 January 2023 18:21
- Hits: 1461
-- Achieved primary endpoint with statistically significant reduction in LDL-C (p < 0.0001) --
-- Median percent change in LDL-C of -59% in combination arm compared to -6% in placebo arm --
-- Favorable safety and tolerability --
-- Data support advancement of fixed-dose combination into bioequivalence and Phase 3 safety and efficacy trials -
NAARDEN, The Netherlands and MIAMI, FL, USA I January 17, 2023 I NewAmsterdam Pharma Company N.V. (Nasdaq:NAMS) (“NewAmsterdam” or the “Company”), a clinical-stage company focused on the research and development of transformative oral therapies for major cardiometabolic diseases, today announced topline results from ROSE2, a Phase 2 clinical trial evaluating obicetrapib, the company’s oral, low-dose and once-daily cholesteryl ester transfer protein (“CETP”) inhibitor, in combination with ezetimibe as an adjunct to high-intensity statin therapy.
Based on the encouraging results observed, NewAmsterdam is now selecting a formulated fixed-dose combination tablet of obicetrapib plus ezetimibe, a non-statin oral LDL-lowering therapy, to be tested in a definitive bioequivalence trial and a Phase 3 safety and efficacy trial.
“Elevated levels of LDL cholesterol (LDL-C) remain a significant public health burden despite the availability of statins. While a range of adjunctive treatments are available, many patients are not able to benefit because these agents either do not sufficiently lower LDL-C or are too expensive,” said Christie Ballantyne, M.D., Chief of Cardiovascular Research and Professor at Baylor College of Medicine. “Today, patients – especially those at high-risk – are typically treated with very high-dose statin therapy, which can be associated with intolerable side effects that limit adherence. Combination regimens comprising low-dose statin therapy plus another LDL-C lowering agent, such as a fixed-dose combination of obicetrapib and ezetimibe, may become a powerful strategy to deliver patients better outcomes, while also increasing their willingness and ability to remain on therapy.”
Topline Data from the ROSE2 Trial
“We are excited to announce topline data from ROSE2, which provide support for our belief that obicetrapib and ezetimibe have distinct, complementary mechanisms of action that, when synergized, have the potential to deliver positive outcomes for patients needing further LDL-C reduction,” said John Kastelein, M.D., Ph.D., FESC, Chief Scientific Officer of NewAmsterdam. “In addition to supporting the development of our fixed-dose combination pill, these results build on prior clinical experience and further characterize obicetrapib as a highly differentiated molecule, with the potential to deliver for the first time the full promise of CETP inhibition.”
ROSE2 (NCT05266586) was designed as a placebo-controlled, double-blind, randomized Phase 2 study to evaluate the efficacy, safety and tolerability of obicetrapib 10 mg in combination with ezetimibe 10 mg as an adjunct to high-intensity statin therapy. A total of 119 patients were randomized to receive combination therapy, obicetrapib 10 mg or placebo for an 84-day treatment period. The primary efficacy endpoint was the percent change from Day 1 to Day 84 in LDL-C for the combination treatment group compared to the placebo group and was met. Patients treated with the combination of obicetrapib and ezetimibe achieved a median reduction in LDL-C of 59%, as compared to patients treated with placebo, who achieved a median reduction in LDL-C of 6%. Overall, the combination of obicetrapib and ezetimibe was observed to be well-tolerated, with a safety profile observed to be comparable to placebo.
“Based on the data from ROSE2, we are now focused on selecting a formulated fixed-dose combination tablet of obicetrapib plus ezetimibe to advance into a definitive bioequivalence study and a Phase 3 trial,” said Michael Davidson, M.D., Chief Executive Officer of NewAmsterdam. “If positive, the results from these trials, coupled with our ongoing BROADWAY, BROOKLYN and PREVAIL studies, if also positive, have the potential to support an application for approval of obicetrapib as an adjunct to maximally tolerated statin therapy and in a fixed-dose combination with ezetimibe. There is a growing consensus that for high-risk patients with atherosclerotic cardiovascular disease (“ASCVD”), the lower the LDL-C, the better. We believe access to a fixed-dose combination of obicetrapib and ezetimibe as an alternative oral therapy for these patients has the potential to support achievement of more aggressive LDL-C targets.”
NewAmsterdam anticipates sharing full data from this Phase 2 clinical trial in a forthcoming publication or in a presentation at an upcoming medical meeting.
Obicetrapib is a next-generation, oral, low-dose CETP inhibitor that the Company is developing to potentially overcome the limitations of current LDL-lowering treatments. The Company believes that obicetrapib has the potential to be a once-daily oral CETP inhibitor for lowering LDL-C, if approved. In the Company’s Phase 2b ROSE trial, obicetrapib demonstrated a 51% lowering of LDL-C from baseline at a 10 mg dose level on top of high-intensity statins. In all three of the Company’s Phase 2 trials, TULIP, ROSE and OCEAN, evaluating obicetrapib as a monotherapy or a combination therapy, the Company observed statistically significant LDL-lowering activity combined with generally moderate side effects and no drug-related, treatment-emergent serious adverse events. Obicetrapib has demonstrated strong tolerability in more than 600 patients with low or elevated lipid levels (“dyslipidemia”) in NewAmsterdam’s clinical trials to date. The Company is conducting two Phase 3 pivotal trials, BROADWAY and BROOKLYN, to evaluate obicetrapib as a monotherapy used as an adjunct to maximally tolerated lipid-lowering therapies to potentially enhance LDL-lowering for high-risk CVD patients. The Company began enrolling patients in BROADWAY in January 2022 and in BROOKLYN in July 2022. The Company also commenced our Phase 3 PREVAIL CVOT in March 2022, which is designed to assess the potential of obicetrapib to reduce occurrences of MACE, including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and non-elective coronary revascularization.
NewAmsterdam (Nasdaq:NAMS) is a clinical-stage biopharmaceutical company whose mission is to improve patient care in populations with metabolic diseases where currently approved therapies have not been sufficiently successful or well tolerated. Based in the Netherlands, NewAmsterdam recently completed a business combination with Frazier Lifesciences Acquisition Corporation (“FLAC”), a special purpose acquisition company sponsored by an affiliate of Frazier Healthcare Partners. Proceeds from this transaction were approximately $328 million, prior to deducting transaction expenses, comprising approximately $93 million in funds from the former FLAC trust account and approximately $235 million from the concurrent, oversubscribed PIPE financing, which was co-led by Frazier Healthcare Partners and Bain Capital Life Sciences and included leading institutional investors. For more information, please visit: www.newamsterdampharma.com.