NewAmsterdam Pharma Reports Positive Results from Phase 2 Study of Oral Obicetrapib Demonstrating Over 50% LDL-Lowering as an Adjunct to High-Intensity Statins
- Category: Small Molecules
- Published on Wednesday, 28 July 2021 16:53
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Median reduction in LDL-c of >50%
Results from ROSE Phase 2 study show for the first time that oral obicetrapib yields significant LDL-c lowering as adjunct to high-intensity statins (HIS)
Well-tolerated oral dose of highly selective CETP inhibitor could address substantial unmet need for patients whose LDL-c levels and cardiovascular risk remain too high despite being treated with maximally tolerated lipid-lowering therapy
Clinical data confirm genetic validation of CETP as an LDL-lowering mechanism, supporting company strategy for developing obicetrapib in cardiovascular diseases and other major diseases of high unmet need
Initiation of Phase 3 registration trials expected in fourth quarter of 2021
NAARDEN, The Netherlands I July 28, 2021 I NewAmsterdam Pharma (NAP), a clinical-stage company focused on the research and development of transformative therapies for cardiometabolic diseases, today announced statistically significant and clinically robust LDL-c lowering results in its recently completed Phase 2 clinical study evaluating oral obicetrapib, an investigational novel selective cholesteryl ester transfer protein (CETP) inhibitor. NAP is developing obicetrapib as an adjunct to maximally tolerated lipid-lowering therapy as a monotherapy and a fixed-dose combination with ezetimibe.
“These clinical data, coupled with our earlier results, support the growing scientific evidence that obicetrapib provides exceptional LDL-c lowering efficacy,” said John Kastelein, MD, PhD, FESC, chief scientific officer of NewAmsterdam Pharma. “We are excited by these results and believe that obicetrapib represents a groundbreaking add-on option for the many patients who cannot get to goal LDL-c despite treatment with maximally tolerated existing lipid-lowering therapy. Data from the ROSE study showed robust LDL-lowering and significant increases in HDL-c, which gives us tremendous confidence that obicetrapib may also be a promising approach for Alzheimer’s disease and diabetes, disorders in which CETP inhibition has been genetically validated.”
Top-line results of the ROSE study show unprecedented effects of CETP inhibition on LDL-c reduction and HDL-c increase attributed to orally administered obicetrapib. Results included reduction of median LDL-c levels by greater than 50% (primary endpoint LS mean LDL-c decreased 44% p < .0001, Shapiro-Wilk Normality Test p=.0001, median LDL-c decreased by 51%). Notably, median baseline LDL-c for participants in the study was 52 mg/dl at day 56 of the study, compared with median LDL-c 94 mg/dl at baseline. The Company plans to initiate Phase 3 registration studies in the fourth quarter of 2021.
ROSE (NCT04753606) was designed as a placebo-controlled, double-blind, randomized, Phase 2 dose-finding study to evaluate the efficacy, safety, and tolerability of obicetrapib as an adjunct to high-intensity statin therapy. A total of 120 patients were randomized to placebo, 5 mg obicetrapib or 10 mg obicetrapib for an 8-week treatment period. The primary endpoint was met for both doses. In the 10 mg dose group, obicetrapib lowered median LDL by 51% (primary endpoint LS mean LDL-c decreased 44% p < .0001, Shapiro-Wilk Normality Test p=.0001, median LDL-c decreased by 51%). Following the treatment period, patients continued for a 4-week safety follow-up and a 15-week PK follow-up. Overall, obicetrapib was well-tolerated compared to placebo.
“We are very enthusiastic about the data from the ROSE trial, as they demonstrate that obicetrapib shows potential to become a highly differentiated oral therapy for additional LDL-c lowering as an adjunct to statins or other lipid lowering therapies,” said Michael Davidson, MD, chief executive officer of NewAmsterdam Pharma. “Over two-thirds of statin-eligible patients are not achieving sufficient LDL-c lowering, leaving them at increased risk for heart attack, stroke and other poor cardiovascular outcomes. Heart disease is still the number one cause of mortality in the U.S. and is indeed on the rise. The medical community recognizes that there is a substantial medical need for a potent, oral, affordable LDL-c lowering treatment option. We believe that obicetrapib has the potential to meet that need for patients,” said Dr. Davidson. “We are looking forward to advancing our development program and expect to initiate Phase 3 registration trials by the end of this year.”
Obicetrapib is a selective cholesteryl ester transfer protein (CETP) inhibitor in development for lowering low-density lipoprotein cholesterol (LDL-c) and preventing major adverse cardiovascular events. Over one hundred million people globally cannot achieve LDL-c goals despite maximally tolerated statin therapy. Obicetrapib was previously tested in TULIP (published in Lancet), a randomized double-blind, placebo-controlled Phase 2a trial in 364 mildly dyslipidemic patients, which showed that obicetrapib is well-tolerated and effectively lowers LDL-c in patients as a monotherapy and in combination with statins. NAP is working to initiate Phase 3 trials in Q4 2021.
About NewAmsterdam Pharma
Founded in 2019 by the venture capital firm Forbion and John Kastelein, NewAmsterdam Pharma is a privately held, clinical-stage company focused on the research and development of transformative therapies for cardiometabolic diseases. Its mission is to improve patient care in populations. In April 2020, NewAmsterdam acquired Dezima Pharma from Amgen, including all rights for obicetrapib (formerly AMG 899, now TA-8995) a selective cholesteryl ester transfer protein (CETP) inhibitor. In January 2021, NewAmsterdam Pharma closed a $196M (€161M) Series A financing led by Morningside Ventures and Ascendant BioCapital with participation from Forbion, Kaiser Foundation Hospitals, BVF Partners L.P., Population Health Partners, LSP Dementia Fund, Peter Thiel, Janus Henderson Investors, Medpace, GL Capital, JVC Investment Partners, and Presight Capital. The Company is investigating obicetrapib as the preferred LDL-c lowering therapy for patients with ASCVD/FH on maximally tolerated statin therapy as well as for the treatment of Alzheimer’s disease and diabetes. NewAmsterdam Pharma is headquartered in Naarden, The Netherlands. For more information, please visit: www.newamsterdampharma.com