Prevail
Cardiovascular Outcome Study to Evlauate the Effect of Obisetrapib in Pateints with Cardiovascular Disease (PREVAIL)
Placebo Controlled, Double Blind, Randomized Cardiovascular Outcome Study to Evaluate the Effect of 10 mg Obicetrapib in Participants With ASCVD Not Adequately Controlled Despite Maximally Tolerated Lipid Modifying Therapies
Patients will be randomized in a 1:1 fashion to obicetrapib 10mg daily vs placebo
Inclusion Criteria:
Exclusion Criteria:
NewAmsterdam Pharma Announces Publication in Nature Medicine Discussing
Clinical Potential of Obicetrapib
-- Full data support the potential of obicetrapib to address unmet medical
need for millions of patients who cannot achieve their LDL-C targets with
high-intensity statin therapy (HIS) alone --
-- Treatment with obicetrapib in patients on high-intensity statin therapy was
observed to have statistically significant impact on LDL-C, as well as
significant impacts on ApoB, non-HDL-C, HDL-C and Lp(a), additional key
measures of cardiovascular disease risk --
-- Publication also details obicetrapib’s unique physiochemical properties,
which enable the potential for improved potency over first-generation CETP
inhibitors --
Business Wire
NAARDEN, Netherlands & MIAMI --
August 11, 2022
NewAmsterdam Pharma (NewAmsterdam), a clinical-stage company focused on the
research and development of transformative oral therapies for metabolic
diseases, today announced the publication of full results from the Phase 2b
Randomized Study of Obicetrapib as an Adjunct to Statin Therapy (ROSE)
clinical trial in the peer-reviewed journal, Nature Medicine. The article,
titled “Lipid lowering effects of the CETP inhibitor obicetrapib in
combination with high-intensity statins: a randomized phase 2 trial,” is
available online at: https://www.nature.com/articles/s41591-022-01936-7.
Obicetrapib is NewAmsterdam’s next-generation oral, low-dose and once-daily
cholesteryl ester transfer protein (CETP) inhibitor, initially in development
for patients at high risk for cardiovascular disease as an adjunct to
maximally tolerated statin therapy, both as a monotherapy and in a fixed-dose
combination with ezetimibe.
In addition to the previously announced data, in which it was observed that
obicetrapib significantly lowered low density lipoprotein cholesterol (LDL-C)
in patients on high-intensity statins (HIS), data published in the Nature
Medicine manuscript included significant observations for other lipid changes
in the treatment arm, which are believed to be clinically meaningful. As
compared to placebo, treatment with obicetrapib led to statistically
significant changes from baseline in apolipoprotein B (ApoB), non-high density
lipoprotein cholesterol (non-HDL-C) concentration, HDL-C concentration and
lipoprotein(a) (Lp(a)), with all effects observed in a dose-dependent manner.
The data below illustrates the median percent change in lipid levels against
baseline as follows:
Lipid Placebo (n=40) Obicetrapib 5 mg (n=40) Obicetrapib 10 mg (n=40)
LDL-C -6.5 -41.5 -50.8
ApoB -2.6 -24.4 -29.8
Non-HDL-C -3.5 -38.9 -44.4
HDL-C -4.9 135.0 165.0
LP(a) 4.0 -33.8 -56.5
Obicetrapib was well tolerated in the trial, with adverse event rates similar
across placebo and obicetrapib arms. Treatment emergent adverse events (TEAEs)
were reported by 15 subjects in the 5 mg group and eight subjects in the 10 mg
group, compared with 19 subjects in the placebo group. TEAEs that were
considered by the investigator to be related to study treatment were reported
by two subjects (one subject in the 5 mg and 10 mg groups, respectively),
compared with four subjects in the placebo group. The majority of TEAEs were
mild and moderate in severity; one subject in the placebo group had a severe
TEAE. The publication also highlights obicetrapib’s unique structural scaffold
and physiochemical properties that enables the potential for it to be a
significantly more potent CETP inhibitor than prior investigational compounds
in the class.
A previously completed multiple ascending dose Phase 1 study of
obicetrapib showed that CETP activity was inhibited by 90.9% and 97.6%,
respectively, for the 5 and 10 mg doses. Although head-to-head clinical trials
have not been conducted to date, these results are markedly greater than the
CETP inhibition observed with anacetrapib and evacetrapib. A potential and
partial explanation for this improved potency is the unique hydrophilic
structure of obicetrapib, which is the most polar of all CETP inhibitors that
have been in the clinic. It also has been observed to have better
bioavailability and greater LDL-C lowering activity at lower doses.
Finally, the publication discusses evidence that the ApoB and LDL-C lowering
effect of CETP inhibitors functions through increased clearance of
ApoB-containing lipoproteins through the liver, the same mechanism of action
as most other lipid lowering therapies. This further supports the belief that
LDL-C lowering via obicetrapib will translate into improved cardiovascular
outcomes for patients.
“The data published in Nature Medicine provide additional evidence that
obicetrapib is a next-generation molecule that is clearly differentiated from
prior CETP inhibitors, with the potential to overcome the safety and efficacy
challenges that have historically limited the potential of the drug class,”
said John Kastelein, M.D., Ph.D., FESC, chief scientific officer of
NewAmsterdam Pharma and author on the Nature Medicine manuscript. “Together,
the full results of ROSE demonstrate that obicetrapib has the potential to
provide significant reductions in LDL-C as an adjunct to high intensity
statins, while also improving other lipid biomarkers, like ApoB and Lp(a),
which are increasingly recognized as important targets in cardiovascular
disease. These data reinforce our confidence that we are advancing a
potentially transformative cardiometabolic therapy, which if approved, could
change the treatment paradigm for millions of patients who are inadequately
managed on HIS therapy alone.”
“There is an urgent need to deliver a new convenient and cost-effective oral
medicine for dyslipidemia, which delivers strong efficacy with a favorable
safety profile,” said Michael Davidson, M.D., Chief Executive Officer at
NewAmsterdam Pharma. “The new data published in Nature Medicine represent a
growing consensus among the medical and research community that obicetrapib
may fulfill this unmet need. We continue to enroll our ongoing Phase 3 studies
and look forward to sharing additional data with the clinical community as we
complete our BROADWAY and BROOKLYN trials, which is expected in 2024.”
NewAmsterdam Pharma is currently evaluating obicetrapib in three Phase 3
clinical trials, BROADWAY (LDL-lowering capability in patients on maximum
tolerated lipid-modifying therapies with established atherosclerotic
cardiovascular disease or heterozygous familial hypercholesterolemia (HeFH)
with LDL-C ≥ 70 mg/dL), BROOKLYN (LDL-lowering capability in HeFH patients on
maximum tolerated lipid-modifying therapies with LDL-C ≥ 70 mg/dL), and
PREVAIL (CVOT in patients on maximum tolerated lipid-modifying with
atherosclerotic cardiovascular disease with LDL-C ≥ 70 mg/dL), and a Phase 2b
trial, ROSE2, which is examining obicetrapib as a fixed-dose combination
therapy with obicetrapib 10 mg and ezetimibe 10 mg in patients on
high-intensity statin therapy with LDL-C ≥ 70 mg/dL.
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