NewAmsterdam Pharma’s push to show a cholesterol drug can prevent Alzheimer’s disease has passed another test. The phase 3 sub-study tracked significant changes in an Alzheimer’s biomarker, adding to evidence that CETP inhibition may cut the risk of developing the neurodegenerative disease.
Transatlantic biotech NewAmsterdam primarily licensed obicetrapib from Amgen to restart the industry’s stalled attempt to establish CETP inhibitors in cardiovascular disease. However, the biotech also spotted chances to expand beyond its core indications, leading it to enroll 1,727 people with Alzheimer’s risk factors in sub-study of its phase 3 obicetrapib.
The sub-study participants were carriers of ApoE3/4 or 4/4. Patients who took obicetrapib for 12 months had significant reductions in the biomarker p-tau217 compared to their counterparts on placebo. The result was statistically significant in the full Alzheimer’s population and in the 367 ApoE4 carriers.
Other researchers have found p-tau217 predicts cognitive decline, but NewAmsterdam is yet to show its drug candidate improves outcomes in people at risk of Alzheimer’s. The sub-study looked at a range of biomarkers beyond p-tau217. NewAmsterdam’s press release lacks data on the secondary endpoints.
NewAmsterdam CEO Michael Davidson, M.D., said in a statement that the “findings strongly support a potential preventive strategy for Alzheimer’s disease.” Shares in the biotech rose 9% to $22 in premarket trading.
Interest in using obicetrapib in Alzheimer’s is mostly built on preclinical and genetic data. Rodents that lack the CETP gene are resistant to Alzheimer’s. Mice with the human CETP gene have more cholesterol in their brains.
Cholesterol is part of a healthy brain—which contains more of the substance than other organs—and is cleared by ApoE. Yet, excess cholesterol in cell membranes may fuel development of amyloid plaques. There is evidence that ApoE4, an Alzheimer’s risk factor, is less effective at clearing cholesterol. As such, NewAmsterdam has proposed that using obicetrapib to remove cholesterol could prevent Alzheimer’s.
The sub-study data add to the results of a phase 2a trial NewAmsterdam ran in 13 patients with early Alzheimer’s and at least one copy of ApoE4. The biotech tracked reductions in cholesterol in plasma and cerebrospinal fluid.