NewAmsterdam drug cuts cholesterol, but by less than expectations, in phase 3 test

NewAmsterdam Pharma’s drug reduced cholesterol in patients with a genetic disorder by 41% at Week 52, confirming the therapy’s efficacy but falling outside of the range shown in a previous study.

The reduction also missed the expectation of analysts, who were hoping to see the value at the high end of a range of 43% to 51%. NewAmsterdam's shares sank 33% in pre-market trading Monday to $12.03, compared to $18.86 at the previous close. 

NewAmsterdam’s obicetrapib previously lowered median LDL cholesterol by 51% when given alone in a phase 2 trial.

Now, the company has revealed the results from the phase 3 BROOKLYN trial, the first of three high-stakes readouts expected for the company over the next three quarters. In this phase 3 test, obicetrapib was used alone in adult patients with heterozygous familial hypercholesterolemia (HeFH) whose cholesterol is not adequately controlled despite being on the maximum tolerated dose of other lipid-lowering medications.

HeFH is a genetic disorder that causes high cholesterol and affects the body’s ability to process it.

In the BROOKLYN trial, obicetrapib led to a mean reduction of 36.3% at Week 12 compared to placebo. At 52 weeks, the value was 41.5%. The therapy also led to reductions in other key biomarkers, including non-HDL-C, ApoB, and Lp(a), meeting statistical significance consistent with other studies.

The therapy was well tolerated, with a discontinuation rate of 7.6% compared to 14.4% in the placebo arm. There were eight severe treatment-emergent adverse events (TEAEs) in each arm, but no severe drug-related TEAEs in either group.

“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,” said CEO Michael Davidson, M.D.

William Blair analysts had been hoping to see a higher reduction with the late-stage trial, with a value above 50% likely to push up the company’s share price.

“We believe confirming this level of LDL-C reduction and safety will be key to building positive momentum ahead of additional phase 3 readouts to come,” the analysts wrote in a  July 24 note. 

The focus now shifts to the rest of the four-pronged clinical program for obicetrapib, which includes three tests with the therapy alone and one in combination with the common cholesterol absorption inhibitor ezetimibe. The studies all include patients whose cholesterol is not well controlled on existing medicines.

A readout from BROADWAY, which is examining the therapy in adults with atherosclerotic cardiovascular disease (ASCVD) and/or HeFH, is expected in the fourth quarter. William Blair is expecting cholesterol reductions of 43% to 45% across the BROADWAY and BROOKLYN studies.

Results from the TANDEM trial are expected in the first quarter of 2025. That study is testing obicetrapib with ezetimibe in patients with established ASCVD or multiple risk factors for ASCVD and/or HeFH.

Finally, there’s PREVAIL, a cardiovascular outcomes trial of obicetrapib in patients with a history of ASCVD. Enrollment of 9,500 patients completed in April, and a readout is expected in 2026.

NewAmsterdam will host a conference call this morning to discuss the BROOKLYN results. Full results from the trial will be presented at an upcoming medical conference.