NewAmsterdam's CETP blocker successful in Phase III HeFH study

NewAmsterdam Pharma reported successful results for its oral CETP inhibitor obicetrapib in the Phase III BROOKLYN trial focusing on patients with heterozygous familial hypercholesterolaemia (HeFH), an inherited high cholesterol condition. The 354-patient study investigated obicetrapib as an additional treatment to maximally tolerated lipid-lowering medications. The results showed a 36.3% reduction in LDL cholesterol (LDL-C) at 12 weeks compared to placebo, which further improved to 41.5% after one year.

The company's CEO, Michael Davidson, expressed satisfaction with the data, noting that the LDL reduction was consistent with Phase II results and highlighted the sustained efficacy over a full year. Davidson emphasized that these outcomes are particularly significant given the challenging patient population, who are already on multiple treatments including high-intensity statins, ezetimibe, and PCSK9 inhibitors.

The BROOKLYN trial also indicated that over half of the participants achieved LDL-C levels below 70 mg/dL, a crucial target for those at high cardiovascular risk. Davidson highlighted that the majority of these maximally treated patients reached their goals with the addition of obicetrapib, an oral medication.

Regarding safety, the trial demonstrated a favorable profile for obicetrapib, with adverse events and discontinuations due to side effects being similar to or lower than those observed with placebo. Specifically, the rate of treatment-related serious adverse events was 5.6% for the obicetrapib group compared to 6.8% for the placebo group, and treatment discontinuation rates were 7.6% versus 14.4%, respectively. The study also found no significant concerns regarding blood pressure, liver enzymes, muscle enzymes, or renal function. Davidson remarked on the drug's tolerability, considering it particularly important given the asymptomatic nature of hypercholesterolemia.

Jefferies analysts, prior to the announcement, projected significant commercial potential for obicetrapib, estimating it could become a $3-4 billion product at its peak. They suggested that positive Phase III results could greatly enhance NewAmsterdam's market value, which currently stands at $1.7 billion, indicating a substantial growth opportunity.

NewAmsterdam is also preparing for additional Phase III results. The larger BROADWAY trial, which is evaluating obicetrapib in patients with established HeFH or atherosclerotic cardiovascular disease (ASCVD) who need further LDL-C reduction, is expected to provide top-line data in the fourth quarter. Another trial, TANDEM, is assessing a fixed-dose combination of obicetrapib and ezetimibe in over 400 patients, with results anticipated in the first quarter of 2025. Additionally, the cardiovascular outcomes trial PREVAIL, which has completed enrolment of over 9500 patients, is ongoing with results expected by late 2026.

As NewAmsterdam strategizes its regulatory approach, it is considering the timing of its filing for LDL indications. Davidson suggested that the company might align its filing with the availability of cardiovascular outcomes data from the PREVAIL trial, which would take at least 2.5 years to complete. The aim is to ensure that outcome data is available at the time of the drug's launch, potentially leading to a filing in late 2025 or early 2026. Davidson emphasized the importance of this timing in the context of current payer and clinician dynamics.