Every 33 seconds, someone in the U.S. dies from cardiovascular disease.
That statistic, part of 2021 data from the Centers for Disease Control and Prevention, represents a larger picture of heart disease in the U.S., where previous progress in the indication has stalled out.
“For the past decade, we’ve seen a reversal in our declines in heart disease. Things have gone backwards when it comes to cardiovascular risk/rates going down,” NewAmsterdam Pharma CEO Michael Davidson, M.D., told Fierce Biotech. “We want to be part of the solution to offset this climb in heart disease risk over the past decade.”
Davidson believes part of the uptick is explained by the lack of proper tools available to treat low-density lipoprotein cholesterol (LDL-C, colloquially known as “bad cholesterol”) more effectively. The CEO hopes NewAmsterdam’s obicetrapib, a CETP inhibitor designed to be a statin add-on, can help reverse that trend.
The biotech shared new data from a phase 2 trial testing obicetrapib—an Amgen castoff—among patients whose LDL-C levels couldn’t be sufficiently lowered with other medications at the 2024 American College of Cardiology annual meeting in Atlanta.
The study, dubbed ROSE2, enrolled 119 patients with LDL cholesterol above 70 mg/dL and triglycerides below 400 mg/dL and assessed obicetrapib as a monotherapy and in combination with ezetimibe, an approved cholesterol-lowering drug. All participants stayed on high-intensity statin therapy after enrolling in the study.
Earlier results found LDL levels in the obicetrapib-ezetimibe combination cohort had fallen by 59% after 12 weeks of daily dosing, compared to a 6% drop in the placebo arm, results that met the trial’s primary endpoint. NewAmsterdam believes the combo has a potential synergistic mechanism of action, with obicetrapib designed to increase the excretion of cholesterol into the intestines and ezetimibe blocking cholesterol reabsorption.
The new data include an analysis of obicetrapib’s impact on small dense LDL-C, a strong predictor of residual risk of future cardiovascular events.
The total data set reveals that obicetrapib as a monotherapy and with ezetimibe, respectively, significantly reduced LDL-C (43.5% and 63.4%), non-HDL-C (37.5% and 55.6%), apolipoprotein B (24.2% and 34.4%), total LDL-P (54.8% and 72.1%), small LDL-P (92.7% and 95.4%), and sdLDL-C (30.9% and 44.4%) while increasing HDL-C (142% and 136%). All measures are statistically significant.
“What we showed in this study is that when you add obicetrapib, a CETP inhibitor, to high intensity statins, it does a great job of addressing that small LDL residual risk burden,” Davidson, who is also a practicing cardiologist and director of the University of Chicago’s lipid clinic, said.
While statins help reduce LDL cholesterol and cardiovascular risk, there’s still a group of patients taking statins with elevated cardiovascular risk, the CEO explained. Statins reduce risk by about 25%, leaving 75% of the risk unaddressed.
Lipid-related risk accounts for a portion of that 75% residual risk because most statins don’t lower small particle count as effectively as they lower larger particles, Davidson said, adding that data demonstrate a larger risk associated with smaller particles than larger particles.
NewAmsterdam Pharma is now setting out to prove that obicetrapib can reduce cardiovascular risk by reducing LDL-C in three ongoing phase 3 trials: two evaluating LDL-C lowering, and a third, 9,000-patient cardiovascular outcomes study.
The trials, dubbed BROADWAY, BROOKLYN and PREVAIL, are all testing obicetrapib as a monotherapy. PREVAIL, the largest of the three with an estimated enrollment of 9,000 patients with atherosclerotic cardiovascular disease, just completed enrollment, according to an April 9 release.
While data from PREVAIL are due in about three years, both BROOKLYN and BROADWAY are slated to read out later this year.
Looking ahead, Davidson thinks obicetrapib, an oral drug, could be a much more accessible, long-term solution for patients if approved. But he’s not getting too far ahead of himself quite yet.
“We want to, obviously, get our phase 3 data and then meet with the FDA to talk about next steps,” Davidson explained.
The CEO said having the outcome data makes a big difference, not only for the patients, but for providers and payers, too, citing “lessons learned” from other lipid launches.
“We don’t want to launch the drug until we have outcome data in hand—in other words, PREVAIL is completed,” Davidson said.