NewAmsterdam drug lowers cholesterol, but not as much as expected, in phase 3 trial

NewAmsterdam Pharma has recently unveiled the outcomes of its phase 3 BROOKLYN trial, marking a significant milestone for its cholesterol-reducing drug, obicetrapib. This trial is one of three crucial evaluations anticipated in the upcoming quarters. In the study, obicetrapib was administered to adult patients with heterozygous familial hypercholesterolemia (HeFH), a genetic disorder characterized by high cholesterol levels that are insufficiently managed by the highest tolerated doses of other lipid-lowering medications.

Heterozygous familial hypercholesterolemia is a genetic condition that impairs the body's ability to process cholesterol, leading to elevated levels. The BROOKLYN trial aimed to assess the efficacy of obicetrapib in reducing cholesterol in these patients. The findings showed that obicetrapib achieved a mean reduction of 36.3% in LDL cholesterol at Week 12 compared to a placebo. By Week 52, the reduction was recorded at 41.5%. These results reflect a substantial decrease in cholesterol levels, although they did not fully reach the expectations set by previous studies or analyst predictions. Previously, in a phase 2 trial, obicetrapib had lowered median LDL cholesterol by 51% when administered alone.

Despite the significant reductions, the results did not meet the high end of the anticipated range of 43% to 51%. This shortfall led to a 33% drop in NewAmsterdam's shares in pre-market trading, bringing the share price down to $12.03 from $18.86 at the previous close. Nonetheless, the therapy's efficacy was evident, as it also significantly reduced other key biomarkers, including non-HDL-C, ApoB, and Lp(a), aligning with outcomes from other studies.

The BROOKLYN trial also highlighted the drug's safety profile. The therapy was well tolerated, with a discontinuation rate of 7.6% in the treatment group compared to 14.4% in the placebo group. Both groups experienced eight severe treatment-emergent adverse events (TEAEs), but there were no severe drug-related TEAEs reported.

Dr. Michael Davidson, CEO of NewAmsterdam Pharma, expressed satisfaction with the results, emphasizing the drug's potential in reducing LDL cholesterol over a year-long period in a difficult-to-treat patient population. However, some analysts, including those from William Blair, had anticipated higher reductions in LDL cholesterol. They believe that confirming this level of reduction and safety is crucial for building positive momentum as additional phase 3 trials are conducted.

NewAmsterdam Pharma's clinical program for obicetrapib involves four trials. Besides the BROOKLYN trial, three other studies are underway. These include BROADWAY, which focuses on adults with atherosclerotic cardiovascular disease (ASCVD) and/or HeFH, with readout expected in the fourth quarter. Analysts foresee cholesterol reductions ranging from 43% to 45% in BROADWAY and BROOKLYN studies.

The TANDEM trial, expected to report results in the first quarter of 2025, is testing obicetrapib in combination with ezetimibe in patients with established ASCVD or multiple risk factors for ASCVD and/or HeFH. Lastly, the PREVAIL trial, a cardiovascular outcomes study of obicetrapib in patients with a history of ASCVD, completed its enrollment of 9,500 patients in April, with results anticipated in 2026.

NewAmsterdam Pharma plans to discuss the BROOKLYN trial results in a conference call this morning, and comprehensive results will be presented at a forthcoming medical conference. The focus now shifts to the outcomes of the remaining trials, which will be critical in determining obicetrapib's future in the market.