A phase 3 trial of NewAmsterdam Pharma’s cholesterol-lowering candidate hit its co-primary endpoints, teeing the biotech up to file for approval. But the company’s stock fell as investors chewed over findings such as a higher rate of discontinuations on a molecule from a class with a troubled history.
The trial enrolled people who had high LDL cholesterol despite taking maximally tolerated lipid-lowering therapy to test a fixed-dose combination of obicetrapib and ezetimibe. Obicetrapib is NewAmsterdam’s investigational CETP inhibitor, while ezetimibe is a cholesterol therapy that was sold as Zetia. Patients received either the combination, one of the drugs as a single agent or placebo on top of their existing therapies.
By Day 84, LDL cholesterol in the combination arm had fallen by 48.6% compared to placebo. The trial also linked the combination to statistically significant reductions in LDL cholesterol compared to either drug as a monotherapy.
NewAmsterdam, which reported another phase 3 win in July, plans to use the data to file for approval. However, as happened in July, the company’s share price fell in the aftermath of the latest phase 3 win. The stock opened down 14% at just above $20 on Wednesday.
CETP inhibitors were the next big thing in cholesterol at one point in the 2010s but lackluster efficacy sank some drug candidates and an increased risk of cardiovascular disease and death torpedoed another prospect. That history is hanging over NewAmsterdam as it heads toward data from a cardiovascular outcomes trial that should show whether obicetrapib is safer and more efficacious than its predecessors.
The phase 3 trial contained some ammunition for people who doubt the hypothesis. In terms of efficacy, NewAmsterdam has typically seen a 35% to 40% reduction in LDL cholesterol in patients who receive its molecule as a monotherapy. In one analysis, the figure in the latest dataset was 31.9%, although execs on a conference call to discuss the data said to focus on the mean number—35.5%—because the other result was affected by dropouts. The execs said the mean is what matters for the outcomes trial.
Drug-related adverse events that led to discontinuations were another focus of the call. The dropout rate in the obicetrapib monotherapy arm was 5.9%. The rate was 2% or lower in the other cohorts. As with the efficacy result, execs flagged the small size of the study as an explanation for the result. There was nothing eventful in any of the safety data, according to the execs.