Incomplete research, nothing here tells us if treatment prevents Alzheimers, so completely fucking useless. Biomarkers do nothing towards recovery!
Heart Drug From Nearly-Forgotten Class May Treat Alzheimer's
Biomarker effects strongest in APOE4 carriers
Median levels of phosphorylated tau protein-217 (p-tau217), a key Alzheimer's biomarker, rose 2.5-fold faster with placebo than with obicetrapib over 12 months, according to Philip Scheltens, MD, PhD, of VU Medical Center in Amsterdam, speaking at the Alzheimer's Association International Conference.
Other biomarkers such as p-tau181 and the ratio of amyloid beta-42 to its 40-residue form (Aβ42/40) also indicated a potential(Research should give us actual and your mentors didn't request that? Bad research!) risk reduction with the drug among more than 1,500 individuals with cardiovascular disease.
This was from a prespecified secondary analysis of data from a cardiovascular-focused trial of obicetrapib called BROADWAY, primary results from which were reported in May. The drug works by blocking conversion of high-density lipoprotein (HDL) cholesterol into the low-density form (LDL). CETP inhibitors were all the rage a few years ago as a novel approach to cholesterol management, but poor results with the first wave of candidates didn't meet expectations. But obicetrapib's developer, Netherlands-based NewAmsterdam Pharma, didn't give up. BROADWAY is one of three phase III trials to examine the drug's safety and efficacy in reducing LDL levels; another trial is underway that will show whether it also reduces major cardiovascular events.
But research on the interplay of cholesterol metabolism and Alzheimer's disease led the company to keep an eye on obicetrapib's effects on Alzheimer's disease biomarkers. "Lipid dysregulation is very important for Alzheimer's disease, it's an important risk factor, especially with APOE4," he told attendees. "Obicetrapib actually has the ability to significantly change p-tau progression over time as compared with placebo."
BROADWAY had a total of 2,530 participants with either familial hypercholesterolemia or established atherosclerotic cardiovascular disease, randomized 2:1 to obicetrapib or placebo for 12 months. Scheltens's presentation focused on 1,515 participants who were designated for Alzheimer's biomarker analyses. Of these, 367 carried at least one copy of the APOE4 gene. Trajectories for p-tau217 and the Aβ42/40 ratio were the primary outcomes.
Patients in the active drug group showed a 1.99% increase in p-tau217 over the year of treatment, compared with 4.98% with placebo (P=0.019); no significant difference in the Aβ42/40 trajectory was seen (-0.44% vs 1.03%, P=0.29).
But an exploratory endpoint, the ratio of p-tau217 to Aβ42/40, did show a very significant difference, with increases of 2.51% with obicetrapib compared with 6.55% in the placebo group (P=0.004).
Differences between groups were also greater in APOE4 carriers. In the latter, p-tau217 increased 1.45% with the drug versus 7.19% with placebo (P=0.022); this pattern was also seen for older APOE4 carriers. The gap grew even larger when Scheltens and colleagues looked at the 29 homozygous APOE4 carriers: a decrease of 7.81% with obicetrapib, compared with a 12.67% spike in the placebo group.
The investigators' belief, Scheltens said, is that these effects are not a consequence of diminished HDL-LDL conversion, but rather some type of direct action on Alzheimer's pathology.
He also noted that safety findings were highly favorable, with no differences from placebo in the BROADWAY sample.
NewAmsterdam has not revealed specific plans for pursuing obicetrapib as an Alzheimer's therapy, concentrating for now in securing approval for cardiovascular indications.
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