NewAmsterdam's Cholesterol Drug Shows Promise in Alzheimer's Prevention

NewAmsterdam Pharma has reported encouraging results from a phase 3 sub-study of its cholesterol-lowering drug obicetrapib, suggesting potential benefits in Alzheimer's disease prevention. The study, which focused on individuals with Alzheimer's risk factors, demonstrated significant reductions in a key biomarker associated with cognitive decline.

Obicetrapib's Impact on Alzheimer's Biomarker

The sub-study, involving 1,727 participants carrying ApoE3/4 or 4/4 genotypes, revealed that patients treated with obicetrapib for 12 months experienced significant decreases in p-tau217 levels compared to those on placebo. This effect was observed in both the overall Alzheimer's population and specifically in the 367 ApoE4 carriers.

P-tau217 is considered a predictor of cognitive decline, and its reduction suggests a potential preventive effect against Alzheimer's disease progression. However, it's important to note that NewAmsterdam has yet to demonstrate improved cognitive outcomes in at-risk individuals.

Mechanism of Action and Preclinical Evidence

Obicetrapib, a CETP inhibitor, was initially developed for cardiovascular indications. However, preclinical and genetic data have suggested a potential role in Alzheimer's prevention. Studies have shown that rodents lacking the CETP gene exhibit resistance to Alzheimer's, while those with the human CETP gene have increased brain cholesterol levels.

The drug's proposed mechanism involves reducing excess cholesterol in cell membranes, which may contribute to amyloid plaque formation. This approach could be particularly beneficial for carriers of ApoE4, a known Alzheimer's risk factor associated with less effective cholesterol clearance.

Market Response and Future Outlook

NewAmsterdam's CEO, Michael Davidson, M.D., expressed optimism about the findings, stating that they "strongly support a potential preventive strategy for Alzheimer's disease." The market responded positively to the news, with NewAmsterdam's stock rising 9% to $22 in premarket trading.

These results build upon earlier phase 2a trial data, which demonstrated reductions in cholesterol levels in both plasma and cerebrospinal fluid among 13 patients with early Alzheimer's and at least one copy of ApoE4. As research progresses, the pharmaceutical industry will be closely watching the development of obicetrapib as a potential breakthrough in Alzheimer's prevention.